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Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.
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Imunoterapia , Lipídeos , RNA , Microambiente Tumoral , Animais , Cães , Feminino , Humanos , Camundongos , Antígenos de Neoplasias/imunologia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Linhagem Celular Tumoral , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Glioblastoma/terapia , Glioblastoma/imunologia , Glioma/terapia , Glioma/imunologia , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Neoplasias/imunologia , RNA/química , RNA/uso terapêutico , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Lipídeos/químicaRESUMO
Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.
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Inibidores de Checkpoint Imunológico , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/imunologia , Humanos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Feminino , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linhagem Celular Tumoral , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Imunoterapia/métodosRESUMO
PURPOSE: Defining how the in vivo immune status of peripheral tissues is shaped by the external environment has remained a technical challenge. We recently developed Functional in vivo confocal microscopy (Fun-IVCM) for dynamic, longitudinal imaging of corneal immune cells in living humans. This study investigated the effect of seasonal-driven environmental factors on the morphodynamic features of human corneal immune cell subsets. DESIGN: Longitudinal, observational clinical study. PARTICIPANTS: Sixteen healthy participants (aged 18-40 years) attended 2 visits in distinct seasons in Melbourne, Australia (Visit 1, November-December 2021 [spring-summer]; Visit 2, April-June 2022 [autumn-winter]). METHODS: Environmental data were collected over each period. Participants underwent ocular surface examinations and corneal Fun-IVCM (Heidelberg Engineering). Corneal scans were acquired at 5.5 ± 1.5-minute intervals for up to 5 time points. Time-lapse Fun-IVCM videos were created to analyze corneal immune cells, comprising epithelial T cells and dendritic cells (DCs), and stromal macrophages. Tear cytokines were analyzed using a multiplex bead-based immunoassay. MAIN OUTCOME MEASURES: Difference in the density, morphology, and dynamic parameters of corneal immune cell subsets over the study periods. RESULTS: Visit 1 was characterized by higher temperature, lower humidity, and higher air particulate and pollen levels compared with Visit 2. Clinical ocular surface parameters and the density of immune cell subsets were similar across visits. At Visit 1 , corneal epithelial DCs were larger, with a lower dendrite probing speed (0.38 ± 0.21 vs. 0.68 ± 0.33 µm/min; P < 0.001) relative to Visit 2; stromal macrophages were more circular and had less dynamic activity (Visit 1, 7.2 ± 1.9 vs. Visit 2, 10.3 ± 3.7 dancing index; P < 0.001). Corneal T cell morphodynamics were unchanged across periods. Basal tear levels of interleukin 2 and CXCL10 were relatively lower during spring-summer. CONCLUSIONS: This study identifies that the in vivo morphodynamics of innate corneal immune cells (DCs, macrophages) are modified by environmental factors, but such effects are not evident for adaptive immune cells (T cells). The cornea is a potential in vivo window to investigate season-dependent environmental influences on the human immune system. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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A new guanidinium-templated vanadate, [C(NH2)3]3VO4·2H2O, has been synthesized in a phase-pure form. It crystallizes in a noncentrosymmetric polar space group, Cc, and the crystal structure is built upon a framework of guanidinium, vanadate tetrahedra, and water molecules linked by hydrogen bonds. Notably, optical measurements reveal that the material exhibits an approximately 9.6-fold enhancement in second-harmonic generation efficiency compared to its phosphate analogue. The enhancement can be attributed to the increased geometrical distortion of the VO4 tetrahedra. Furthermore, we found that the coordination number of the central vanadium atom significantly affects the optical band gaps. Among various coordination numbers, the 4-coordinate VO4 tetrahedra are found to be more favorable for widening the optical band gap of materials compared to the 5- and 6-coordinate vanadium polyhedra, as demonstrated by this work.
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PURPOSE: This study aimed to investigate the prescription of beta-blockers (ß-blockers) for patients with asthma. METHODS: In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, ß-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a ß-blocker and an asthma medication were co-prescribed in one billing statement or when separate ß-blocker and asthma prescriptions had overlapping dates of use. RESULTS: In the 1027 patients with asthma who were prescribed non-selective ß-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective ß-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. ß2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. CONCLUSIONS: Carvedilol and propranolol accounted for half of all ß-blockers prescribed to asthma patients. Prescribing ß-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between ß-blockers and co-prescribed asthma medications.
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Antagonistas Adrenérgicos beta , Asma , Humanos , Asma/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Estudos Retrospectivos , Estudos Transversais , Masculino , Feminino , República da Coreia , Pessoa de Meia-Idade , Adulto , Idoso , Prescrições de Medicamentos/estatística & dados numéricos , Adulto Jovem , Antiasmáticos/uso terapêutico , Antiasmáticos/administração & dosagem , Padrões de Prática Médica/estatística & dados numéricos , AdolescenteRESUMO
AIMS: This study determined the optimal positive end-expiratory pressure levels in infants in supine and prone positions under general anesthesia using electrical impedance tomography (EIT). METHODS: This prospective observational single-centre study included infants scheduled for surgery in the prone position. An electrical impedance tomography sensor was applied after inducing general anesthesia. The optimal positive end-expiratory pressure in the supine position was determined in a decremental trial based on EIT and compliance. Subsequently, the patient's position was changed to prone. Electrical impedance tomography parameters, including global inhomogeneity index, regional ventilation delay, opening pressure, the centre of ventilation, and pendelluft volume, were continuously obtained up to 1 h after prone positioning. The optimal positive end-expiratory pressure in the prone position was similarly determined. RESULTS: Data from 30 infants were analyzed. The mean value of electrical impedance tomography-based optimal positive end-expiratory pressure in the prone position was significantly higher than that in the supine position [10.9 (1.6) cmH2O and 6.1 (0.9) cmH2O, respectively (p < .001)]. Significant differences were observed between electrical impedance tomography- and compliance-based optimal positive end-expiratory pressure. Peak and mean airway, plateau, and driving pressures increased 1 h after prone positioning compared with those in the supine position. In addition, the centre of ventilation for balance in ventilation between the ventral and dorsal regions improved. CONCLUSION: The prone position required higher positive end-expiratory pressure than the supine position in mechanically ventilated infants under general anesthesia. EIT is a promising tool to find the optimal positive end-expiratory pressure, which needs to be individualized.
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Anestesia Geral , Impedância Elétrica , Respiração com Pressão Positiva , Tomografia , Humanos , Respiração com Pressão Positiva/métodos , Anestesia Geral/métodos , Decúbito Ventral/fisiologia , Decúbito Dorsal , Lactente , Estudos Prospectivos , Masculino , Feminino , Tomografia/métodos , Recém-NascidoRESUMO
INTRODUCTION: This study aimed to assess the impact of positive-end-expiratory pressure (PEEP) on the non-hypoxic apnea time in infants during anesthesia induction with an inspired oxygen fraction of 0.8. METHODS: This age stratified randomized controlled trial included patients under 1 year of age. Preoxygenation was performed using an inspired oxygen fraction of 0.8 for 2 min. Inspired oxygen fraction of 0.8 was administered via a face mask with volume-controlled ventilation at a tidal volume of 6 mL.kg-1, with or without 7 cmH2O of PEEP. Tracheal intubation was performed after 3 min of ventilation; however, it was disconnected from the breathing circuit. Ventilation was resumed once the pulse oximetry readings reached 95%. The primary outcome was the non-hypoxic apnea time, defined as the time from the cessation of ventilation to achieving a pulse oximeter reading of 95%. The secondary outcome measures included the degree of atelectasis assessed by ultrasonography and the presence of gastric air insufflation. RESULTS: Eighty-four patients were included in the final analysis. In the positive end-expiratory pressure group, the atelectasis score decreased (17.0 vs. 31.5, p < .001; mean difference and 95% CI of 11.6, 7.5-15.6), while the non-hypoxic apnea time increased (80.1 s vs. 70.6 s, p = .005; mean difference and 95% CI of -9.4, -16.0 to -2.9), compared to the zero end-expiratory pressure group, among infants who are 6 months old or younger, not in those aged older than 6 months. DISCUSSION: The application of positive end-expiratory pressure reduced the incidence of atelectasis and extended the non-hypoxic apnea time in infants who are 6 months old or younger. However, it did not affect the incidence of atelectasis nor the non-hypoxic apnea time in patients aged older than 6 months.
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BACKGROUND: Optimal pain management after insertion of a central venous catheter in children remains unclear. AIM: This study aimed to evaluate the effects of a selective supraclavicular nerve block on postoperative analgesia in pediatric patients undergoing hickman catheter or chemoport insertion. METHODS: Fifty patients aged 3-18 years scheduled for elective Hickman or chemoport insertion were randomized into two groups of 25 each: one group received an ultrasound-guided selective supraclavicular nerve block with 0.1 mL/kg of 0.5% ropivacaine (SSCNB group), and the other group did not receive a nerve block (control group). The primary outcome was the postoperative Wong-Baker Faces Pain Rating Scale score measured between 10 and 30 min after surgery. Secondary outcomes included pain scores at 1, 3, and 24 h after the surgery, block-related complications, length of stay in the postanesthesia care unit, postoperative analgesic consumption, and time to first analgesic use 24 h after surgery. RESULTS: The worst pain score within 30 min in the recovery room was significantly lower in the SSCNB group compared to the control group (6 [5-7] vs. 3 [2-4]; median difference, -3; 95% CI, -4 to -1; p < .001). Pain scores at 1, 3, and 24 h after surgery were also significantly lower in the SSCNB group. The need for both opioid and non-opioid analgesics in the postoperative period was significantly lower in the SSCNB group (36.0% vs. 0%; p = .002 and 44.0% vs. 16.0%; mean difference, -28%; 95% CI, -56 to 0.19; p = .033, respectively), while other secondary outcomes were not significantly different between the two groups. CONCLUSIONS: Ultrasound-guided SSCNB is an effective method for managing postoperative pain in children undergoing Hickman catheter or chemoport insertion, reducing the need for analgesics within 24 h after surgery.
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Bloqueio do Plexo Braquial , Cateteres Venosos Centrais , Humanos , Criança , Anestésicos Locais/uso terapêutico , Cateteres Venosos Centrais/efeitos adversos , Ultrassonografia de Intervenção/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Bloqueio do Plexo Braquial/efeitos adversos , Analgésicos , Analgésicos OpioidesRESUMO
BACKGROUND: The effectiveness of head mounted real-time ultrasound displays (hereafter referred to as 'smart glasses') in improving hand-eye coordination in less experienced individuals, such as trainees in anaesthesia, is unclear. OBJECTIVES: To compare the first-attempt success rate of smart glasses-assisted ultrasound-guided paediatric radial artery catheterisation with conventional ultrasound guided catheterisation performed by anaesthesiology trainees. DESIGN: Prospective randomised controlled trial. SETTINGS: Tertiary university hospital from September 2021 to February 2023. PATIENTS: One hundred and twenty-two paediatric patients (age <7âyears, weight ≥3âkg) who required radial artery cannulation during general anaesthesia. INTERVENTIONS: The participants were randomly assigned to either the ultrasound screen group (control) or the smart glasses group prior to radial artery catheterisation. MAIN OUTCOME MEASURES: The primary outcome was the first attempt success rate. Secondary outcomes included the number of attempts, use of transfixion technique, overall complication rate, and clinical anaesthesiology (CA) year of the operators. RESULTS: A total of 119 paediatric patients were included in the analysis. The smart glasses group exhibited higher first-attempt success rate than did the control group (89.8% [53/59] vs. 71.7% [43/60]; P â=â0.023; odds ratio (OR) 3.49; (95% confidence interval (CI) 1.27-9.6). The overall number of attempts [median, 1; interquartile range (IQR), 1-1; range, 1-3 vs. median, 1; IQR, 1-2; range, 1-4; P â = â0.006], use of transfixion technique (12/59 [20.3%] vs. 28/60 [46.7%]; P â=â0.002), and overall complication rate (6.8% [4/59] vs. 30.0% [18/60]; P â=â0.002) were lower in the smart glasses group than in the control group. However, among paediatric anaesthesiology fellows (CA 5âyears), the first- (89.3% [25/28] vs. 80.8% [21/26]; P â=â0.619) and second-attempt success rates (96.4% [27/28] vs. 80.8% [21/26]; P â=â0.163) did not differ between the two groups. CONCLUSIONS: Smart glasses-assisted ultrasound guided radial artery catheterisation improved the first attempt success rate among anaesthesiology trainees, reducing the number of attempts and overall complication rates in small paediatric patients. Smart glasses were more effective for anaesthesia residents (CA 2-4âyears) but were not effective for paediatric anaesthesiology fellows (CA 5âyears). TRIAL REGISTRATION: ClinicalTrials.gov (NCT05030649) ( https://classic.clinicaltrials.gov/ct2/show/NCT05030649 ).
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Anestesiologia , Cateterismo Periférico , Artéria Radial , Ultrassonografia de Intervenção , Humanos , Artéria Radial/diagnóstico por imagem , Feminino , Masculino , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Cateterismo Periférico/métodos , Anestesiologia/educação , Pré-Escolar , Criança , Lactente , Óculos Inteligentes , Anestesia Geral , Competência Clínica , CabeçaRESUMO
BACKGROUND: The potential benefits of Analgesia Nociception Index guided intra-operative analgesia on intra-operative opioid consumption remains to be demonstrated in paediatric anaesthesia. OBJECTIVES: This study aimed to explore the effects of Analgesia Nociception Index guided analgesia on sufentanil consumption during anaesthesia and postoperative pain scores in paediatric patients with moyamoya disease. DESIGN: A prospective randomised controlled study. SETTING: Seoul National University Children's Hospital, Seoul, Republic of Korea. PATIENTS: A total of 40 children scheduled for encephaloduroarteriosynangiosis. MAIN OUTCOME MEASURES: The primary outcome was total intra-operative sufentanil consumption, and the secondary outcomes included postoperative pain scores and incidence of opioid-related adverse events. RESULTS: The Analgesia Nociception Index group showed lower intra-operative sufentanil consumption (in µgâkg -1 âh -1 ) compared with the Standard group (0.30â±â0.12 and 0.39â±â0.17, respectively; mean difference, -0.09; 95% confidence interval, -0.19 to 0.00; P â=â0.049). Postoperatively, compared with the Standard group, the Analgesia Nociception Index group reported lower median pain scores at 18 and 24âh and maximum pain within 24âh (1 [0 to 2] vs. 3 [2 to 5]; P â=â0.004, 1 [0 to 2] vs. 3 [1 to 4]; P â=â0.041, and 4 [3 to 5] vs. 5 [4 to 7]; P â=â0.045, respectively), with fewer patients experiencing nausea (3 [15%] vs. 10 [50%], P â=â0.043). CONCLUSION: The Analgesia Nociception Index guided analgesic protocol can reduce intra-operative sufentanil consumption and postoperative pain within 24âh with fewer nausea symptoms in paediatric patients with moyamoya disease who undergo encephaloduroarteriosynangiosis. TRIAL REGISTRATION NUMBER: NCT05672212.
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Analgésicos Opioides , Doença de Moyamoya , Nociceptividade , Dor Pós-Operatória , Sufentanil , Humanos , Doença de Moyamoya/cirurgia , Feminino , Masculino , Criança , Estudos Prospectivos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Sufentanil/administração & dosagem , Nociceptividade/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Pré-Escolar , Analgesia/métodos , Medição da Dor/métodos , Adolescente , Resultado do TratamentoRESUMO
BACKGROUND: The association between the concentration of atmospheric particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia in children receiving general anaesthesia is unclear. OBJECTIVE: To investigate the association between the exposure to particulate matter on the day of surgery and the occurrence of intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% for more than 1âmin, in children. DESIGN: Retrospective study. SETTING: Single-centre. PARTICIPANTS: Children aged 18âyears or younger who received general anaesthesia between January 2019 and October 2020. INTERVENTION: Information on daily levels of particulate matter with a diameter 10âµm or less and 2.5âµm or less measured within a neighbourhood corresponding to the area defined by the hospital's zip code was obtained from publicly available air-quality data. MAIN OUTCOME MEASURES: The primary outcome was intra-operative hypoxaemia, defined as a pulse oximetry oxygen saturation of less than 90% lasting for more than 1âmin, manually verified by anaesthesiologists using vital sign registry data extracted at 2âs intervals. RESULTS: Of the patients finally analysed, 3.85% (489/13â175) experienced intra-operative hypoxaemia. Higher levels of particulate matter 10âµm or less in diameter (≥81âµgâm -3 , 17/275, 6.2%) were associated with an increased occurrence of intra-operative hypoxaemia compared with lower particulate matter concentrations [<81âµgâm -3 , 472/12â900, 3.7%; adjusted odds ratio, 1.71; 95% confidence interval (CI), 1.04 to 2.83; P â=â0.035]. CONCLUSION: The level of particulate matter on the day of surgery pose a risk of intra-operative hypoxaemia in children receiving general anaesthesia. If the concentrations of particulate matter 10âµm or less in diameter on the day of surgery are high, children receiving general anaesthesia should be managed with increased caution.
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Anestesia Geral , Hipóxia , Material Particulado , Humanos , Anestesia Geral/efeitos adversos , Estudos Retrospectivos , Material Particulado/efeitos adversos , Hipóxia/epidemiologia , Hipóxia/etiologia , Hipóxia/induzido quimicamente , Hipóxia/sangue , Masculino , Feminino , Criança , Pré-Escolar , Lactente , República da Coreia/epidemiologia , Adolescente , Oximetria , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/induzido quimicamente , Recém-Nascido , Saturação de OxigênioRESUMO
BACKGROUND: Hypoxaemia occurs frequently during paediatric laryngeal microsurgery. OBJECTIVE: The oxygen reserve index is a noninvasive and continuous parameter to assess PaO2 levels in the range of 100 to 200âmmHg. It ranges from 0 to 1.0. We investigated whether monitoring the oxygen reserve index can reduce the incidence of SpO2 90% or less. DESIGN: Randomised controlled trial. SETTING: A tertiary care paediatric hospital. PARTICIPANTS: Paediatric patients aged 18âyears or less scheduled to undergo laryngeal microsurgery. INTERVENTION: The patients were randomly allocated to the oxygen reserve index or control groups, and stratified based on the presence of a tracheostomy tube. Rescue intervention was performed when the oxygen reserve index was 0.2 or less and the SpO2 was 94% or less in the oxygen reserve index and control groups, respectively. MAIN OUTCOME MEASURE: The primary outcome was the incidence of SpO2 90% or less during the surgery. RESULTS: Data from 88 patients were analysed. The incidence of SpO2 ≤â90% did not differ between the oxygen reserve index and control groups [Pâ=â0.114; 11/44, 25% vs. 18/44, 40.9%; relative risk: 1.27; and 95% confidence interval (CI): 0.94 to 1.72]. Among the 128 rescue interventions, SpO2 ≤â90% event developed in 18 out of 75 events (24%) and 42 out of 53 events (79.2%) in the oxygen reserve index and control groups, respectively (Pâ<â0.001; difference: 55.2%; and 95% CI 38.5 to 67.2%). The number of SpO2 ≤â90% events per patient in the oxygen reserve index group (median 0, maximum 3) was less than that in the control group (median 0, maximum 8, Pâ=â0.031). CONCLUSION: Additional monitoring of the oxygen reserve index, with a target value of greater than 0.2 during paediatric airway surgery, alongside peripheral oxygen saturation, did not reduce the incidence of SpO2 ≤â90%.
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Hipóxia , Saturação de Oxigênio , Humanos , Masculino , Feminino , Hipóxia/prevenção & controle , Hipóxia/sangue , Hipóxia/etiologia , Pré-Escolar , Oxigênio/sangue , Criança , Lactente , Microcirurgia/métodos , Laringe , Oximetria/métodos , Monitorização Intraoperatória/métodos , AdolescenteRESUMO
INTRODUCTION: In this study, we compared the dentitional changes after Invisalign and conventional orthodontic treatment with 4 first premolar extractions. METHODS: This retrospective study included 57 patients whose orthodontic treatment involved the extraction of 4 first premolars because of bialveolar protrusion. A total of 27 patients were treated with Invisalign (mean age, 25.5 ± 5.2 years) and 30 patients with the fixed appliance (mean age, 24.4 ± 5.8 years). The angular and linear changes of the maxillary and mandibular central incisors, second premolars, first molars, and second molars were measured from the recordings on the basis of the lateral cephalograms taken before and after treatment. The angular changes of the canines and second premolars were measured using panoramic radiographs. RESULTS: The overbite and interincisal angle increased significantly in the Invisalign group compared with in the conventional fixed appliance group (P <0.05). The maxillary central incisors showed increased lingual tipping in the Invisalign group (P <0.05), whereas there was no statistically significant difference in the angular change of the mandibular incisors between groups (P >0.05). The maxillary first and second molars showed mesial tipping in the Invisalign group (P <0.05). The maxillary second premolars, first and second molars, and the mandibular second molars showed mesial movement in the Invisalign group (P <0.05). CONCLUSIONS: The Invisalign group showed more statistically significant lingual tipping of the maxillary central incisors, distal tipping of the maxillary canines, and mesial tipping of the maxillary first and second molars after maximum retraction of the anterior teeth compared with the fixed appliance group.
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Aparelhos Ortodônticos Removíveis , Técnicas de Movimentação Dentária , Humanos , Adulto Jovem , Adulto , Adolescente , Dente Pré-Molar/diagnóstico por imagem , Dente Pré-Molar/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Maxila/diagnóstico por imagem , Aparelhos Ortodônticos Fixos , CefalometriaRESUMO
PURPOSE: The anterior belly of the digastric muscle (ABDM) is the target of botulinum toxin injection; however, anatomical considerations related to the injection point are absent. This study used Sihler's staining to analyze the intramuscular nerve distribution of ABDM to identify the most effective botulinum toxin injection points. METHODS: We used 12 specimens from 6 embalmed cadavers in this study. The specimens were manually dissected to preserve the mylohyoid nerve and subjected to Sihler's staining. From the gnathion to and hyoid bone, the ABDM was divided into three equal parts, distinguishing the anterior, middle, and posterior thirds. RESULTS: Only a branch of the mylohyoid nerve entered the ABDM, and its entry point was located in the middle-third region in all cases. The nerve endings were concentrated in the middle third (100%), followed by the anterior third (58.3%) and were not observed in the posterior third. CONCLUSION: The landmarks used in this study (gnathion and hyoid bone) are easily palpable on the skin surface, allowing clinicians to target the most effective injection site (middle third of ABDM). These results provide scientific and anatomic evidence for injection points, and will aid in the management of ABDM injection procedures in clinical practice.
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Cadáver , Humanos , Masculino , Feminino , Injeções Intramusculares/métodos , Idoso , Músculos do Pescoço/inervação , Músculos do Pescoço/anatomia & histologia , Músculos do Pescoço/efeitos dos fármacos , Coloração e Rotulagem/métodos , Idoso de 80 Anos ou mais , Toxinas Botulínicas/administração & dosagem , Pontos de Referência AnatômicosRESUMO
Developing both conceptual and procedural knowledge is important for students' mathematics competence. This study examined whether Grade 9 general education mathematics teachers' self-reported use of concept-focused instruction (CFI) and procedure-focused instruction (PFI) were associated differently with ninth graders' algebra achievement after 2.5 years, depending on students' mathematics difficulty (MD) status. Data for this study were drawn from the High School Longitudinal Study for the years 2009-2010 and 2011-2012 (N = 19,104). Multiple regression analyses indicated that students with MD who participated in Grade 9 mathematics classrooms where teachers self-reported the use of less CFI and more PFI were more positively associated with having higher algebra achievement after 2.5 years. Conversely, students without MD in classrooms where mathematics teachers self-reported the use of more CFI and less PFI were positively associated with having higher algebra achievement after 2.5 years. However, this study's findings do not suggest that teachers should disregard CFI and provide only PFI when teaching students with MD. Because the data set did not include any variable to discover whether teachers provided sufficient support (i.e., evidence-based practices) for students with MD, who have more constraints in their cognitive skills compared to students without MD, to benefit from CFI, the findings of this study should be interpreted cautiously. Directions for future research and practical implications are discussed.
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The prevalence of obesity is gradually increasing in South Korea, and the coronavirus disease 2019 (COVID-19) pandemic has accelerated the weight gain. In response to COVID-19, South Korea implemented targeted distancing measures based on the number of COVID-19 cases, rather than a full lockdown. This study focused on two subgroups that influence the rise in obesity prevalence during the early stages of the COVID-19 pandemic and explored the factors contributing to rapid weight gain in this group during this period. This cross-sectional study involved 3,462 participants recruited through the MicroEmbrain Inc. Online survey panel. Participation emails were sent by the research company to the online survey panel, and individuals who voluntarily agreed to participate responded to the survey. The participants consisted of residents aged 19 and above from Seoul, with sample distribution taking considering sex, age, and region. Height, and weight before and during the COVID-19 pandemic were self-reported. The analysis revealed that compared with that of pre-COVID-19 statistics, 11 % of all participants entered the overweight or obese categories post COVID-19, and among those who were overweight or obese before COVID-19, 42.5 % reported weight gain. Both groups had relatively younger individuals, higher stress levels, spent more time alone, and had increased usage of online platforms including online food purchasing. Post-COVID-19 wt gain among individuals with pre-existing overweight or obesity status was associated with a higher frequency of solitary drinking (odds ratio [OR] = 1.407, 95 % confidence interval [CI] = 1.024-1.932), increased online leisure time (OR = 1.336, 95 % CI = 1.063-1.678), and increased use of meal delivery services (OR = 1.307, 95 % CI = 1.026-1.664). The prevalence of obesity has continued to rise after COVID-19 pandemic, highlighting the need for interventions that mitigate the negative impact of the pandemic on health behavior.
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Background/Objectives: This study evaluates the safety and surgical outcomes of performing robotic hysterectomy on uteri weighing over 1000 g, with a focus on the surgeon's learning curve. Methods: A retrospective analysis was conducted on 44 patients who underwent hysterectomy by a single surgeon from January 2020 to February 2024 using the DaVinci Xi System. Surgical procedures included total hysterectomy with bilateral salpingectomy, and specimens were removed via transvaginal manual morcellation. Operative times were segmented into docking, console, morcellation, and conversion times. Results: Results indicated an inflection point in the 20th case, suggesting proficiency after 20 surgeries. Comparison between early (Group A, cases 1-20) and later cases (Group B, cases 21-44) showed significant reductions in console time (CT) and morcellation time (MT) in Group B, leading to a shorter overall operative time (OT). Although estimated blood loss was higher in Group A, it was not statistically significant. Hemoglobin differences were significantly higher in Group B. No significant differences were observed in transfusion rates, postoperative analgesic usage, or complications between the groups. Conclusions: The study concludes that robotic hysterectomy for large uteri is safe and that surgical proficiency improves significantly after 20 cases, enhancing overall outcomes.
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Despite existing empirical work that explores the multiple ways in which students develop a sense of belonging in higher education, there is a dearth of comparative research about the extent to which the concepts of community and belonging are central to what it means to be a student and how students in different national contexts (beyond Anglophone countries) construct community and belonging. Drawing on qualitative data from students from six European countries, we provide an account of conceptualisations of community and belonging. Specifically, this paper extends discussions around community and belonging in higher education through comparative inquiry. Notwithstanding the individualised and consumerist framing of students accompanied by market reforms in higher education across Europe, it shows that the notion of community and/or belonging features prominently in students' narratives. We also demonstrate how a sense of community and belonging is experienced on different levels. Crucially, the emphasis placed on community in students' sense of belonging varies by the country, pointing towards the continued influence of distinctive national traditions, structures and norms of higher education. Our analysis contributes to wider debates about the development of a European Higher Education Area and its impact on European homogenisation.
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In this study, an investigation was conducted into the types of attitudes that parents may have of gifted students and gifted education, and the predictors of these attitudes. Using data collected from 331 parents of students enrolled in a Christian faith-based school system in one of the eight states/territories of Australia, multiple analyses, including exploratory factor analysis and latent profile analysis, were performed. The results revealed three subgroups of parents, each representing distinct attitude profiles (i.e., "strong", "moderate" and "weak" supporters of gifted students and gifted education). Furthermore, we found nine variables to be potential predictors of parent attitudes, including perceptions of the giftedness of one's child, and the anticipated socio-emotional and academic impacts of giftedness and gifted education. Some of the important contributions of the study to the research literature included the distinction made by parents between attitudes toward gifted education adaptations and attitudes toward special gifted education settings, and the comparatively large number of parents who are moderately (rather than strongly or weakly) supportive of gifted students and gifted education.