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1.
Med Princ Pract ; 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37549659

RESUMO

Background The relationship between overweight or obesity and low back pain (LBP) has previously been investigated. Several recent studies have focused on the relationship between other indicators of obesity, particularly indicators of fat and the risk of LBP. However, the results of body composition and LBP have been inconsistent. Methods All data for the present retrospective, cross-sectional study was extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) versions V-1 and 2 conducted in 2010 and 2011 by the Korean Centers for Disease Control and Prevention. In KNHANES V-1 (2010) and V-2 (2011), those over 50 years of age completed the surveys on LBP, body weight, and body composition assessed using dual-energy X-ray absorptiometry (DXA) were included. The multivariable logistic regression analysis was used to examine the relationship between the presence of chronic LBP and body composition adjusting for confounders. Results We analyzed 3,579 persons who completed the question. In the multivariable analyses adjusting for age and sex, none of the variables, including fat mass and fat-free mass, remained positively or negatively associated with LBP. Additionally, when depression, smoking, alcohol intake, physical activity, diabetes mellitus, and fat or lean tissue mass were included in the multivariable logistic model, no significant associations were found between all measures of fat mass, fat-free mass, and LBP Conclusion This study is contrary to previous studies that concluded that there is a correlation between obesity and fat mass and LBP. LBP is not associated with increased levels of obesity and fat mass.

2.
Medicina (Kaunas) ; 59(12)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38138152

RESUMO

Background and Objectives: Supine-to-prone hypotension is caused by increased intrathoracic pressure and decreased venous return in the prone position. Dynamic arterial elastance (Eadyn) indicates fluid responsiveness and can be used to predict hypotension. This study aimed to investigate whether Eadyn can predict supine-to-prone hypotension. Materials and Methods: In this prospective, observational study, 47 patients who underwent elective spine surgery in the prone position were enrolled. Supine-to-prone hypotension is defined as a decrease in Mean Arterial Pressure (MAP) by more than 20% in the prone position compared to the supine position. Hemodynamic parameters, including systolic blood pressure (SAP), diastolic blood pressure, MAP, stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index, cardiac index, dP/dt, and hypotension prediction index (HPI), were collected in the supine and prone positions. Supine-to-prone hypotension was also assessed using two different definitions: MAPprone < 65 mmHg and SAPprone < 100 mmHg. Hemodynamic parameters were analyzed to determine the predictability of supine-to-prone hypotension. Results: Supine-to-prone hypotension occurred in 13 (27.7%) patients. Eadyn did not predict supine-to-prone hypotension [Area under the curve (AUC), 0.569; p = 0.440]. SAPsupine > 139 mmHg (AUC, 0.760; p = 0.003) and dP/dtsupine > 981 mmHg/s (AUC, 0.765; p = 0.002) predicted supine-to-prone hypotension. MAPsupine, SAPsupine, PPVsupine, and HPIsupine predicted MAPprone <65 mm Hg. MAPsupine, SAPsupine, SVVsupine, PPVsupine, and HPIsupine predicted SAPprone < 100 mm Hg. Conclusions: Dynamic arterial elastance did not predict supine-to-prone hypotension in patients undergoing spine surgery. Systolic arterial pressure > 139 mmHg and dP/dt > 981 mmHg/s in the supine position were predictors for supine-to-prone hypotension. When different definitions were employed (mean arterial pressure < 65 mmHg in the prone position or systolic arterial pressure < 100 mmHg in the prone position), low blood pressures in the supine position were related to supine-to-prone hypotension.


Assuntos
Hipotensão , Humanos , Estudos Prospectivos , Hipotensão/etiologia , Pressão Sanguínea , Hemodinâmica , Volume Sistólico/fisiologia
3.
Proc Natl Acad Sci U S A ; 116(9): 3524-3529, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30733287

RESUMO

RAP1-interacting adapter molecule (RIAM) mediates RAP1-induced integrin activation. The RAS-association (RA) segment of the RA-PH module of RIAM interacts with GTP-bound RAP1 and phosphoinositol 4,5 bisphosphate but this interaction is inhibited by the N-terminal segment of RIAM. Here we report the structural basis for the autoinhibition of RIAM by an intramolecular interaction between the IN region (aa 27-93) and the RA-PH module. We solved the crystal structure of IN-RA-PH to a resolution of 2.4-Å. The structure reveals that the IN segment associates with the RA segment and thereby suppresses RIAM:RAP1 association. This autoinhibitory configuration of RIAM can be released by phosphorylation at Tyr45 in the IN segment. Specific inhibitors of focal adhesion kinase (FAK) blocked phosphorylation of Tyr45, inhibited stimulated translocation of RIAM to the plasma membrane, and inhibited integrin-mediated cell adhesion in a Tyr45-dependent fashion. Our results reveal an unusual regulatory mechanism in small GTPase signaling by which the effector molecule is autoinhibited for GTPase interaction, and a modality of integrin activation at the level of RIAM through a FAK-mediated feedforward mechanism that involves reversal of autoinhibition by a tyrosine kinase associated with integrin signaling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Integrinas/química , Proteínas de Membrana/química , Conformação Proteica , Proteínas de Ligação a Telômeros/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Adesão Celular/genética , Membrana Celular/química , Cristalografia por Raios X , Proteína-Tirosina Quinases de Adesão Focal/química , Proteína-Tirosina Quinases de Adesão Focal/genética , GTP Fosfo-Hidrolases/química , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas de Membrana/genética , Fosforilação , Complexo Shelterina , Transdução de Sinais , Proteínas de Ligação a Telômeros/genética
4.
Anesth Analg ; 133(3): 690-697, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33591115

RESUMO

BACKGROUND: Tools for the evaluation of gastric emptying have evolved over time. The purpose of this study was to show that the risk of pulmonary aspiration is not increased with carbohydrate drink, by demonstrating that the gastric antral cross-sectional area (CSA) of the NO-NPO group is either equivalent to or less than that of the NPO (nil per os) group. METHODS: Sixty-four patients scheduled for elective laparoscopic benign gynecologic surgery were enrolled and randomly assigned to the NPO group (n = 32) or the NO-NPO group (n = 32). After having a regular meal until midnight before surgery, the NPO group fasted until surgery, while the NO-NPO group ingested 400 mL of a carbohydrate drink at midnight and freely up to 2 hours before anesthesia. The primary outcome was the gastric antral CSA by gastric ultrasound in right lateral decubitus position (RLDP). Noninferiority was defined as a mean difference of CSA <2.8 cm2. Secondary outcomes included CSA in supine position, gastric volume (GV), GV per weight (GV/kg), GV/kg >1.5 mL/kg, and Perlas grade. RESULTS: CSA in RLDP was not different between the NPO group (6.25 ± 3.79 cm2) and the NO-NPO group (6.21 ± 2.48 cm2; P = .959). The mean difference of CSA in RLDP (NO-NPO group - NPO group) was 0.04 (95% confidence interval [CI], -1.56 to 1.64), which was within the noninferiority margin of 2.8 cm2. CSA was not different between the 2 groups (4.17 ± 2.34 cm2 in NPO group versus 4.28 ± 1.23 cm2 in NO-NPO group; P = .828). GV in NPO group (70 ± 56 mL) was not different from NO-NPO group (66 ± 36 mL; mean difference, 3.66; 95% CI, -20 to 27; P = .756). GV/kg in the NPO group (1.25 ± 1.00 mL/kg) was not different from the NO-NPO group (1.17 ± 0.67 mL/kg; P = .694). The incidence of GV/kg > 1.5 mL/kg was not different between NPO (31.3%) and NO-NPO group (21.9%; P = .768). The median (interquartile range) of the Perlas grade was 1 (0-1) in NPO group and 0.5 (0-1) in NO-NPO group (P = .871). CONCLUSIONS: Preoperative carbohydrates ingested up to 2 hours before anesthesia do not delay gastric emptying compared to midnight fasting, as evaluated with gastric ultrasound.


Assuntos
Bebidas , Carboidratos da Dieta/administração & dosagem , Esvaziamento Gástrico , Cuidados Pré-Operatórios , Aspiração Respiratória de Conteúdos Gástricos/prevenção & controle , Estômago/diagnóstico por imagem , Ultrassonografia , Adulto , Bebidas/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Método Duplo-Cego , Feminino , Conteúdo Gastrointestinal , Procedimentos Cirúrgicos em Ginecologia , Humanos , Laparoscopia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/efeitos adversos , Estudos Prospectivos , Aspiração Respiratória de Conteúdos Gástricos/etiologia , Aspiração Respiratória de Conteúdos Gástricos/fisiopatologia , Medição de Risco , Fatores de Risco , Seul , Estômago/fisiopatologia , Fatores de Tempo
5.
J Minim Invasive Gynecol ; 28(5): 1086-1094.e1, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33310170

RESUMO

STUDY OBJECTIVE: To determine whether carbohydrate loading improves the postoperative quality of recovery (QoR) better than the midnight fasting policy in laparoscopic gynecologic surgeries. DESIGN: Randomized, parallel-group trial. SETTING: Tertiary university hospital. PATIENTS: Female patients scheduled for laparoscopic gynecologic surgery for nonmalignant gynecologic diseases. INTERVENTIONS: Eighty-eight women were randomly assigned to the midnight fasting group (nil per os, NPO group) or the carbohydrate loading group (carbohydrate group). Patients in both groups adhered to the enhanced recovery after surgery protocol except for carbohydrate intake in the carbohydrate group. MEASUREMENTS AND MAIN RESULTS: The postoperative QoR was evaluated using the QoR 15-item questionnaire on postoperative day 2. The times to readiness for discharge of the groups were compared. The QoR 15-item questionnaire scores were 97.7 ± 23.0 in the NPO group and 99.6 ± 22.4 in the carbohydrate group; they were not statistically different (p = .702). The times to readiness for discharge of both groups were also not different: 36.8 ± 12.2 hours in the NPO group and 37.6 ± 11.8 hours in the carbohydrate group (p = .684). CONCLUSION: The benefit of carbohydrate beverage intake was not significant in laparoscopic gynecologic surgeries when following the enhanced recovery after surgery protocol.


Assuntos
Doenças dos Genitais Femininos , Laparoscopia , Dieta da Carga de Carboidratos , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Dor Pós-Operatória , Período Pós-Operatório
6.
Medicina (Kaunas) ; 57(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34833448

RESUMO

Background and Objectives: Chronic lower back pain (LBP) is a common clinical disorder. The early identification of patients who will develop chronic LBP would help develop preventive measures and treatment. We aimed to develop machine learning models that can accurately predict the risk of chronic LBP. Materials and Methods: Data from the Sixth Korea National Health and Nutrition Examination Survey conducted in 2014 and 2015 (KNHANES VI-2, 3) were screened for selecting patients with chronic LBP. LBP lasting >30 days in the past 3 months was defined as chronic LBP in the survey. The following classification models with machine learning algorithms were developed and validated to predict chronic LBP: logistic regression (LR), k-nearest neighbors (KNN), naïve Bayes (NB), decision tree (DT), random forest (RF), gradient boosting machine (GBM), support vector machine (SVM), and artificial neural network (ANN). The performance of these models was compared with respect to the area under the receiver operating characteristic curve (AUROC). Results: A total of 6119 patients were analyzed in this study, of which 1394 had LBP. The feature selected data consisted of 13 variables. The LR, KNN, NB, DT, RF, GBM, SVM, and ANN models showed performances (in terms of AUROCs) of 0.656, 0.656, 0.712, 0.671, 0.699, 0.660, 0.707, and 0.716, respectively, with ten-fold cross-validation. Conclusions: In this study, the ANN model was identified as the best machine learning classification model for predicting the occurrence of chronic LBP. Therefore, machine learning could be effectively applied in the identification of populations at high risk of chronic LBP.


Assuntos
Dor Lombar , Idoso , Teorema de Bayes , Humanos , Modelos Logísticos , Dor Lombar/diagnóstico , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Aprendizado de Máquina , Inquéritos Nutricionais
7.
Br J Anaesth ; 125(6): 935-942, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32958203

RESUMO

BACKGROUND: The perfusion index (PI), calculated from the photoplethysmographic waveform, reflects peripheral vasomotor tone. As such, the PI serves as a surrogate for quantitative measures of drug-induced vasoconstriction or vasodilation. This study aimed to compare the effect on the PI of desflurane and sevoflurane at equi-anaesthetic concentrations in patients undergoing single-agent inhalation anaesthesia, where equi-anaesthetic dose was based on the known minimum alveolar concentration of these agents. METHODS: We randomly allocated patients scheduled for arthroscopic knee surgery to receive either desflurane or sevoflurane general anaesthesia after target-controlled induction of anaesthesia with propofol. Anaesthesia was maintained at age-corrected minimum alveolar concentration 1.0, under neuromuscular block (rocuronium). The PI and haemodynamic data were recorded every minute for 35 min after induction of anaesthesia and after standardised nociceptive stimulation. The primary outcome was PI, compared between the groups over time (repeated-measures analysis of variance). Secondary outcomes included MAP and HR. RESULTS: Sixty-nine participants (mean [range] age: 42 yr [19-65 yr]; 49% females) were assigned to either desflurane (n=34) or sevoflurane (n=35). The PI remained higher under desflurane compared with sevoflurane, both before (mean difference [MD]: 3.3; 95% confidence intervals [CIs]: 2.0-4.7; P<0.001) and after tetanic stimulation (MD: 2.8; 95% CI: 2.0-3.7; P<0.001). Higher PI paralleled lower MAP in participants assigned to desflurane anaesthesia (P<0.001), both before (MD: 8 mm Hg; 95% CI: 4-12) and after nociceptive stimulation (MD: 14 mm Hg; 95% CI: 7-22). HR was similar throughout. CONCLUSIONS: These findings suggest that at equipotent doses, desflurane exerts more potent vasodilatory properties and lowers blood pressure by a magnitude potentially associated with harm. CLINICAL TRIAL REGISTRATION: NCT03570164.


Assuntos
Anestésicos Inalatórios/farmacologia , Desflurano/farmacologia , Hemodinâmica/efeitos dos fármacos , Sevoflurano/farmacologia , Vasodilatadores/farmacologia , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
8.
J Korean Med Sci ; 35(26): e225, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627441

RESUMO

BACKGROUND: Spinal nerve ligation (SNL) model is one of the representative models of the neuropathic pain model. Neuropathic pain in a chronic post-ischemic pain (CPIP) mimics the symptoms of complex regional pain syndrome (CRPS). The administration of polydeoxyribonucleotide (PDRN), which has regenerative and anti-inflammatory effects, has been studied and is used in clinical practice treating various diseases. However, the analgesic effect of PDRN in a neuropathic pain or CRPS model remains unknown. METHODS: PDRN (3.3, 10, and 20 mg/kg) was administered into the subcutaneous (SC) layer of the hind paws of SNL and CPIP models. Mechanical anti-allodynic effects were then investigated using the von Frey test. In the immunohistochemical examination, dorsal root ganglia (DRG) and the spinal cord were harvested and examined for the expression of glial fibrillary acidic protein (GFAP) after the 20 mg PDRN injection. RESULTS: Mechanical allodynia was significantly alleviated by administration of PDRN in SNL and CPIP mice at all of the time point. As the dose of PDRN increased, the effect was greater. The 20 mg PDRN injection was found to have the most effective anti-allodynic effect. The increased expression of GFAP in DRG and the spinal cord of SNL and CPIP model decreased following the administration of PDRN than vehicle. CONCLUSION: SC administration of PDRN results in the attenuation of allodynia and activation of astrocytes in neuropathic pain or CRPS models. We propose that PDRN can have significant potential advantages in neuropathic pain treatment.


Assuntos
Síndromes da Dor Regional Complexa/tratamento farmacológico , Neuralgia/tratamento farmacológico , Polidesoxirribonucleotídeos/uso terapêutico , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Síndromes da Dor Regional Complexa/patologia , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/patologia , Medula Espinal/metabolismo , Nervos Espinhais/cirurgia
9.
J Anesth ; 34(1): 59-65, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31701308

RESUMO

PURPOSE: Emergence delirium (ED) is common in children after sevoflurane anesthesia and should be prevented for patient safety. A prospective, double-blind, randomized, controlled study was performed to compare the efficacy of minimal dosage of midazolam versus dexmedetomidine to prevent ED in children undergoing tonsillectomy. METHODS: Seventy children aged 24 months to 12 years were allocated to receive midazolam (0.03 mg/kg) or dexmedetomidine (0.3 µg/kg) 5 min before the end of surgery. The incidence and severity of ED were assessed using a four-point scale and the pediatric anesthesia emergence delirium scale, respectively. The emergence time and postoperative pain scores were also evaluated. RESULTS: The incidence of ED was 31.3% in the midazolam group and 26.5% in the dexmedetomidine group (P = 0.668). The severity of ED was similar in both groups (9.6 ± 5.8 in the midazolam group, vs. 8.1 ± 5.9 in the dexmedetomidine group, P = 0.299). The emergence time was comparable in the two groups [11.0 (8.3-13.8) min in midazolam group vs. 12.0 (10.0-13.5) min in dexmedetomidine group (P = 0.218)]. Postoperative pain score was higher in the midazolam group [0 (0-1)] than in the dexmedetomidine group [0 (0-0)] (P = 0.011). CONCLUSION: Dexmedetomidine and midazolam at single minimum dosages had equal effectiveness to prevent ED in children without delaying emergence time, when administered at the end of surgery. With regards to postoperative analgesic efficacy, although dexmedetomidine showed statistically significant higher analgesic effect than midazolam, further clinical investigations are needed to validate our findings.


Assuntos
Dexmedetomidina , Delírio do Despertar , Criança , Método Duplo-Cego , Delírio do Despertar/epidemiologia , Delírio do Despertar/prevenção & controle , Humanos , Hipnóticos e Sedativos/efeitos adversos , Lactente , Midazolam , Estudos Prospectivos
10.
Surg Endosc ; 33(3): 870-878, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30014331

RESUMO

BACKGROUND: Intraperitoneal isotonic saline instillation (SI) and pulmonary recruitment maneuver (RM) were indicated to alleviate post-laparoscopic shoulder pain (PLSP) effectively. The aim of this study was to compare the effects of the single strategy using SI alone and the combined strategy using SI and RM on PLSP reduction. METHODS: Subjects undergoing elective gynecologic laparoscopy were randomly allocated to a control group (no intervention, n = 48) and two intervention groups (single strategy of SI alone, n = 48; combined strategy of SI and RM, n = 48). In the control group, carbon dioxide was removed only via passive evacuation through the port sites at the completion of the laparoscopic procedure. In the saline instillation group, 20-mL/kg of body weight SI was performed. In the combined strategy group, RM using five pulmonary inflations was performed, in addition to SI. The PLSP scores, which were the primary outcome, were recorded using a visual analog scale postoperatively. RESULTS: The PLSP scores 24 and 48 h after surgery were significantly lower in the two intervention groups than in the control group (P = 0.014 and P = 0.001, respectively), while no significant differences were observed between the two intervention groups. CONCLUSIONS: The single strategy using SI alone is as effective as the combined strategy of SI and RM for removing residual carbon dioxide and consequently preventing PLSP. Therefore, considering the potential risks of pulmonary or hemodynamic complications associated with RM, the single strategy using SI alone might be a better choice than the combined strategy.


Assuntos
Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Insuflação/métodos , Laparoscopia/efeitos adversos , Dor Pós-Operatória , Solução Salina/uso terapêutico , Adulto , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Instilação de Medicamentos , Laparoscopia/métodos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Peritônio/efeitos dos fármacos , Dor de Ombro/etiologia , Dor de Ombro/fisiopatologia , Dor de Ombro/prevenção & controle , Resultado do Tratamento
11.
Int J Syst Evol Microbiol ; 67(10): 4240-4245, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28920849

RESUMO

A Gram-stain-negative, motile-by-gliding, aerobic, non-spore-forming, rod-shaped and yellow-pigmented bacterium was isolated from Salicornia herbacea in the Yellow Sea and designated as strain MBLN091T. It belonged to the family Flavobacteriaceae. The 16S rRNA gene sequence of this isolated strain was similar to that of Flavimarina pacifica IDSW-73T with 94.8 % similarity, and with 92.3-92.8 % similarities to those of other closely related species of the genus Leeuwenhoekiella. The similarities of the RNA polymerase subunit B gene between this strain and F. pacifica KCTC 32466T and Leeuwenhoekiella marinoflava DSM 3653T were 80.5 and 80.2 %, respectively. Growth of strain MBLN091T was observed in the presence of 0.5‒15.0 % (w/v) NaCl at 4‒35 °C and pH 6.0-8.0, with optimal growth in the presence of 2.5‒5.0 % (w/v) NaCl at 20‒25 °C and pH 7.0. This isolate was able to hydrolyse gelatin. The only respiratory quinone was MK-6. The major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and two unidentified lipids. Major fatty acids of the isolate were iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C17 : 0 3-OH and iso-C15 : 1 G. The genomic DNA G+C content was 39.6 mol%. The physiological features were closely related to F. pacifica. Therefore, strain MBLN091T is considered to represent a novel species within the genus Flavimarina, for which the name Flavimarina flava sp. nov. is proposed. The type strain is MBLN091T (=KCTC 52527T=JCM 31731T).


Assuntos
Chenopodiaceae/microbiologia , Flavobacteriaceae/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/genética , Flavobacteriaceae/isolamento & purificação , Fosfatidiletanolaminas/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
12.
Mol Cancer ; 13: 36, 2014 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-24568192

RESUMO

BACKGROUND: The ataxia-telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells. METHODS: Lung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue. RESULTS: Transient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM phosphorylation and increased apoptosis. CONCLUSIONS: cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-κB in lung cancer cells.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , AMP Cíclico/metabolismo , Neoplasias Pulmonares/genética , Proteína Fosfatase 2/biossíntese , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linhagem Celular Tumoral , AMP Cíclico/genética , Dano ao DNA/efeitos da radiação , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Fosforilação/genética , Fosforilação/efeitos da radiação , Proteína Fosfatase 2/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação
13.
J Thorac Dis ; 16(6): 3644-3654, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38983158

RESUMO

Background: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure. However, some patients still experience severe pain after VATS. Pain after VATS can disturb deep breathing and coughing, and can increase postoperative pulmonary complications. Therefore, multidisciplinary pain management is emphasized for enhanced recovery after VATS. Nefopam is a centrally-acting, non-opioid, non-steroidal analgesic drug, and its pain reduction effect in many surgeries has been reported. We sought to determine whether administration of nefopam is effective as multimodal analgesia in VATS. Methods: This study enrolled patients aged 19 years or older, and scheduled for elective VATS lobectomy with American Society of Anesthesiologists (ASA) physical class I-III. Forty-six participants were randomly divided into a group receiving nefopam (group N), and a control group (group O) in a 1:1 ratio. The study participants, and the researcher collecting the data were blinded to the group allocation. For the group N, nefopam 20 mg was administered before surgical incision and also at the end of surgery while chest tube was inserted. For the group O, normal saline 100 mL was administered. The primary outcome of this study was the pain score, by verbal numerical rating scale, at rest and upon coughing. Results: Forty-five participants (group N =22, group O =23) were involved in the statistical analysis. Nefopam reduced pain at rest at 0 h [8 (IQR, 5-10) vs. 4 (IQR, 2-7), P=0.01], and at 0-1 h [5 (IQR, 5-8) vs. 3 (IQR, 2-5), P=0.001]. Pain upon coughing decreased with nefopam at 0 h [9 (IQR, 6-10) vs. 6 (IQR, 2-8), P=0.009], 0-1 h [6 (IQR, 5-8) vs. 5 (IQR, 2-6), P=0.001], and at 12-24 h [4 (IQR, 3-7) vs. 3 (IQR, 1-4), P=0.03]. Injection of 20 mg of nefopam before incision and at the end of surgery relieved postoperative pain at 0 h, 1 h at rest and at 0 h, 1 h, 12-24 h with coughing after VATS. Conclusions: Therefore, nefopam can serve as a useful component of multimodal analgesia for pain management after VATS. Trial Registration: ClinicalTrials.gov (NCT05173337).

14.
Structure ; 31(8): 948-957.e3, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37369205

RESUMO

Integrins are ubiquitously expressed cell-adhesion proteins. Activation of integrins is triggered by talin through an inside-out signaling pathway, which can be driven by RAP1-interacting adaptor molecule (RIAM) through its interaction with talin at two distinct sites. A helical talin-binding segment (TBS) in RIAM interacts with both sites in talin, leading to integrin activation. The bispecificity inspires a "double-hit" strategy for inhibiting talin-induced integrin activation. We designed an experimental peptidomimetic inhibitor, S-TBS, derived from TBS and containing a molecular staple, which leads to stronger binding to talin and inhibition of talin:integrin interaction. The crystallographic study validates that S-TBS binds to the talin rod through the same interface as TBS. Moreover, the helical S-TBS exhibits excellent cell permeability and effectively suppresses integrin activation in cells in a talin-dependent manner. Our results shed light on a new class of integrin inhibitors and a novel approach to design multi-specific peptidomimetic inhibitors.


Assuntos
Peptidomiméticos , Talina , Talina/química , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas de Membrana/química , Peptidomiméticos/farmacologia , Integrinas/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo
15.
Hawaii J Health Soc Welf ; 82(8): 183-187, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37559693

RESUMO

There is an estimated shortage of 46 000 to 90 000 physicians in the US, especially in rural areas. Physicians working in rural areas often maintain a larger scope of practice compared to their urban counterparts. This scope may include performing procedures which may require additional training, and lack of that training may limit rural physicians' capability to perform procedures. Physicians practicing in rural areas of Hawai'i were surveyed about their scope of practice regarding procedures and the perceived hindrances in performing procedures. Physicians identified as rural practitioners and rural physicians attending local conferences were asked to participate. Forty-seven (out of 301) rural Hawai'i physicians participated in the survey, of which 89% reported performing procedures. The most common procedures performed included suture removal, incision and drainage, wound care, and suturing. Of the 47 respondents, a total of 28 physicians or 60% reported wishing to perform procedures but not doing so. The procedures physicians would like to perform included gynecological (36%), casting (21%) and wound care (14%). Barriers to performing procedures included lack of time (51%), inadequate training (37%), out of practice (22%), and poor reimbursement (17%). While most rural physicians in this study perform procedures, many would like to perform more. Lack of training and support are significant barriers to increasing scope of procedures performed. Medical schools, residencies, and continuing education programs should consider expanding training in these areas, especially for those planning to practice or currently practicing in rural areas.


Assuntos
Internato e Residência , Médicos , Humanos , Havaí , Inquéritos e Questionários , População Rural
16.
Sci Rep ; 13(1): 5156, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36991074

RESUMO

Endotracheal tube (ET) misplacement is common in pediatric patients, which can lead to the serious complication. It would be helpful if there is an easy-to-use tool to predict the optimal ET depth considering in each patient's characteristics. Therefore, we plan to develop a novel machine learning (ML) model to predict the appropriate ET depth in pediatric patients. This study retrospectively collected data from 1436 pediatric patients aged < 7 years who underwent chest x-ray examination in an intubated state. Patient data including age, sex, height weight, the internal diameter (ID) of the ET, and ET depth were collected from electronic medical records and chest x-ray. Among these, 1436 data were divided into training (70%, n = 1007) and testing (30%, n = 429) datasets. The training dataset was used to build the appropriate ET depth estimation model, while the test dataset was used to compare the model performance with the formula-based methods such as age-based method, height-based method and tube-ID method. The rate of inappropriate ET location was significantly lower in our ML model (17.9%) compared to formula-based methods (35.7%, 62.2%, and 46.6%). The relative risk [95% confidence interval, CI] of an inappropriate ET location compared to ML model in the age-based, height-based, and tube ID-based method were 1.99 [1.56-2.52], 3.47 [2.80-4.30], and 2.60 [2.07-3.26], respectively. In addition, compared to ML model, the relative risk of shallow intubation tended to be higher in the age-based method, whereas the risk of the deep or endobronchial intubation tended to be higher in the height-based and the tube ID-based method. The use of our ML model was able to predict optimal ET depth for pediatric patients only with basic patient information and reduce the risk of inappropriate ET placement. It will be helpful to clinicians unfamiliar with pediatric tracheal intubation to determine the appropriate ET depth.


Assuntos
Intubação Intratraqueal , Traqueia , Criança , Humanos , Estudos Retrospectivos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Fatores de Risco
17.
Medicine (Baltimore) ; 102(16): e33595, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37083808

RESUMO

This study aimed to compare gastric ultrasound assessments between young and elderly patients, to determine whether the cross-section area (CSA) cutoff values for elderly and young patients should be different, and to suggest CSA cutoff values for elderly patients. This study evaluated the data of 120 patients who underwent elective surgery under general anesthesia between July 2019 and August 2020. Demographic and gastric ultrasound assessment data were retrieved. Patients were divided into the elderly group (n = 58, age: ≥65 years) and young group (n = 62, age: <65 years). The CSAs in the supine and right lateral decubitus positions (RLDP), semiquantitative 3-point Perlas grade (grades 0, 1, and 2), and gastric volume (GV) were determined. CSAs according to different Perlas grades were compared between the 2 groups. To compare normally and non-normally distributed continuous data, Student t test and the Mann-Whitney U test were used, respectively. Categorical data were compared using the chi-square test or Fisher exact test, as appropriate. The receiver operating characteristic (ROC) curves were built for the CSAs to predict pulmonary aspiration. The CSA cutoff values for predicting a high risk of pulmonary aspiration in both the groups were determined. Among patients with Perlas grade 0, the CSAsupine (P = .002) and CSARLDP (P = .002) were greater in the elderly group than in the young group. The specificity, positive predictive value, and accuracy of the CSA decreased when the CSA cutoff value for the young group was applied to the elderly group. The CSA cutoff values for the elderly group were: CSAsupine, 6.92 cm2 and CSARLDP, 10.65 cm2. The CSA of the empty stomach was greater in elderly patients than in young patients. We suggest that the following CSA cutoff values should be used for predicting pulmonary aspiration risk in elderly patients: CSAsupine, 6.92 cm2 and CSARLDP, 10.65 cm2.


Assuntos
Conteúdo Gastrointestinal , Antro Pilórico , Idoso , Humanos , Pessoa de Meia-Idade , Antro Pilórico/diagnóstico por imagem , Estudos Prospectivos , Conteúdo Gastrointestinal/diagnóstico por imagem , Estômago/diagnóstico por imagem , Ultrassonografia
18.
Biochem Biophys Res Commun ; 422(2): 256-62, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22575451

RESUMO

Cyclic AMP is involved in the regulation of metabolism, gene expression, cellular growth and proliferation. Recently, the cAMP signaling system was found to modulate DNA-damaging agent-induced apoptosis by regulating the expression of Bcl-2 family proteins and inhibitors of apoptosis. Thus, we hypothesized that the cAMP signaling may modulate DNA repair activity, and we investigated the effects of the cAMP signaling system on γ-ray-induced DNA damage repair in lung cancer cells. Transient expression of a constitutively active mutant of stimulatory G protein (GαsQL) or treatment with forskolin, an adenylyl cyclase activator, augmented radiation-induced DNA damage and inhibited repair of the damage in H1299 lung cancer cells. Expression of GαsQL or treatment with forskolin or isoproterenol inhibited the radiation-induced expression of the XRCC1 protein, and exogenous expression of XRCC1 abolished the DNA repair-inhibiting effect of forskolin. Forskolin treatment promoted the ubiquitin and proteasome-dependent degradation of the XRCC1 protein, resulting in a significant decrease in the half-life of the protein after γ-ray irradiation. The effect of forskolin on XRCC1 expression was not inhibited by PKA inhibitor, but 8-pCPT-2'-O-Me-cAMP, an Epac-selective cAMP analog, increased ubiquitination of XRCC1 protein and decreased XRCC1 expression. Knockdown of Epac1 abolished the effect of 8-pCPT-2'-O-Me-cAMP and restored XRCC1 protein level following γ-ray irradiation. From these results, we conclude that the cAMP signaling system inhibits the repair of γ-ray-induced DNA damage by promoting the ubiquitin-proteasome dependent degradation of XRCC1 in an Epac-dependent pathway in lung cancer cells.


Assuntos
AMP Cíclico/metabolismo , Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Raios gama , Humanos , Proteólise , Ubiquitina/metabolismo , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
19.
Nat Med ; 11(4): 387-93, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15793581

RESUMO

The bone morphogenetic proteins (BMPs) profoundly affect embryonic development, differentiation and disease. BMP signaling is suppressed by cysteine-rich domain proteins, such as chordin, that sequester ligands from the BMP receptor. We describe a novel protein, KCP, with 18 cysteine-rich domains. Unlike chordin, KCP enhances BMP signaling in a paracrine manner. Smad1-dependent transcription and phosphorylated Smad1 (P-Smad1) levels are increased, as KCP binds to BMP7 and enhances binding to the type I receptor. In vivo, Kcp(-/-) mice are viable and fertile. Because BMPs have a pivotal role in renal disease, we examined the phenotype of Kcp(-/-) mice in two different models of renal injury. Kcp(-/-) animals show reduced levels of P-Smad1, are more susceptible to developing renal interstitial fibrosis, are more sensitive to tubular injury and show substantial pathology after recovery. The data indicate an important role for KCP in attenuating the pathology of renal fibrotic disease.


Assuntos
Fibrose/prevenção & controle , Rim/patologia , Sequência de Aminoácidos , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Cisteína , Proteínas de Ligação a DNA/metabolismo , Proteínas do Olho/farmacologia , Camundongos , Mutação , Células NIH 3T3 , Proteínas do Tecido Nervoso/farmacologia , Estrutura Terciária de Proteína , Proteínas/farmacologia , Alinhamento de Sequência , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad , Proteína Smad1 , Transativadores/metabolismo , Proteínas de Xenopus/farmacologia
20.
Medicine (Baltimore) ; 101(46): e31592, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401493

RESUMO

BACKGROUND: The usefulness of the oxygen reserve index (ORi) in reducing hyperoxemia remains unclear. We designed this study to investigate whether fraction of inspired oxygen (FiO2) adjustment under a combination of ORi and peripheral oxygen saturation (SpO2) guidance can reduce intraoperative hyperoxemia compared to SpO2 alone. METHODS: In this prospective, double-blind, randomized controlled study, we allocated patients scheduled for laparoscopic gastrectomy to the SpO2 group (FiO2 adjusted to target SpO2 ≥ 98%) or the ORi-SpO2 group (FiO2 adjusted to target 0 < 0 ORi < .3 and SpO2 ≥ 98%). The ORi, SpO2, FiO2, arterial partial pressure of oxygen (PaO2), and incidence of severe hyperoxemia (PaO2 ≥ 200 mm Hg) were recorded before and 1, 2, and 3 hours after surgical incision. Data from 32 and 30 subjects in the SpO2 and ORi-SpO2 groups, respectively, were analyzed. RESULTS: PaO2 was higher in the SpO2 group (250.31 ± 57.39 mm Hg) than in the ORi-SpO2 group (170.07 ± 49.39 mm Hg) 1 hour after incision (P < .001). PaO2 was consistently higher in the SpO2 group than in the ORi-SpO2 group, over time (P = .045). The incidence of severe hyperoxemia was higher in the SpO2 group (84.4%) than in the ORi-SpO2 group (16.7%, P < .001) 1 hour after incision. Higher FiO2 was administered to the SpO2 group [52.5 (50-60)] than the ORi-SpO2 group [40 (35-50), P < .001] 1 hour after incision. SpO2 was not different between the 2 groups. CONCLUSION: The combination of ORi and SpO2 guided FiO2 adjustment reduced hyperoxemia compared to SpO2 alone during laparoscopic gastrectomy.


Assuntos
Laparoscopia , Oxigênio , Humanos , Oximetria , Estudos Prospectivos , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos
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