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1.
Zygote ; 30(1): 103-110, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34176529

RESUMEN

This study was performed to improve production efficiency at the level of recipient pig and donor nuclei of transgenic cloned pigs used for xenotransplantation. To generate transgenic pigs, human endothelial protein C receptor (hEPCR) and human thrombomodulin (hTM) genes were introduced using the F2A expression vector into GalT-/-/hCD55+ porcine neonatal ear fibroblasts used as donor cells and cloned embryos were transferred to the sows and gilts. Cloned fetal kidney cells were also used as donor cells for recloning to increase production efficiency. Pregnancy and parturition rates after embryo transfer and preimplantation developmental competence were compared between cloned embryos derived from adult and fetal cells. Significantly higher parturition rates were shown in the group of sows (50.0 vs. 4.1%), natural oestrus (20.8 vs. 0%), and ovulated ovary (16.7 vs. 5.6%) compared with gilt, induced and non-ovulated, respectively (P < 0.05). When using gilts as recipients, final parturitions occurred in only the fetal cell groups and significantly higher blastocyst rates (15.1% vs. 21.3%) were seen (P < 0.05). Additionally, gene expression levels related to pluripotency were significantly higher in the fetal cell group (P < 0.05). In conclusion, sows can be recommended as recipients due to their higher efficiency in the generation of transgenic cloned pigs and cloned fetal cells also can be recommended as donor cells through correct nuclear reprogramming.


Asunto(s)
Clonación de Organismos , Técnicas de Transferencia Nuclear , Animales , Animales Modificados Genéticamente , Blastocisto , Femenino , Fibroblastos , Embarazo , Sus scrofa , Porcinos
2.
Dysphagia ; 37(5): 1112-1119, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34546446

RESUMEN

Dysphagia can be classified as oropharyngeal or esophageal, and functional or structural deficits of the esophagus can cause esophageal dysphagia. Dysphagia aortica (DA) is defined as dysphagia caused by extrinsic compression of the esophagus by the aorta. The aim of this study was to investigate the characteristics of DA by comparing the findings of videofluoroscopic swallowing studies (VFSS) with those of other dysphagia. Sixty-seven patients with postoperative dysphagia aortica (PDA), dysphagia after brainstem infarction (DBI), dysphagia after anterior cervical discectomy and fusion (DACDF), and subjective swallowing difficulty (SSD) without penetration and/or aspiration, who had undergone VFSS incorporating tests using 5 ml of thin and thick liquids, were included. The clinical data were collected retrospectively. The penetration-aspiration scale, functional dysphagia scale (FDS), esophageal transit time (ETT), and aortic lesion parameters (maximal diameter and distance between the lesion and the apex of the aortic arch) were assessed. The patients with PDA had higher FDS scores than the patients with SSD and lower scores than the patients with DBI did on thin liquids, while the FDS scores on thick liquids were lower in the patients with PDA than in those with DBI or DACDF. The patients with PDA had longer ETT than the other three groups. No correlation was found between the aortic lesion parameters and the VFSS findings. Although PDA has some oropharyngeal symptoms, the esophageal phase was affected mainly by PDA. After an operation on the aorta, VFSS should be considered before resuming oral feeding.


Asunto(s)
Trastornos de Deglución , Fusión Vertebral , Deglución , Trastornos de Deglución/diagnóstico , Humanos , Estudios Retrospectivos , Fusión Vertebral/efectos adversos
3.
Knee Surg Sports Traumatol Arthrosc ; 30(8): 2846-2853, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34984529

RESUMEN

PURPOSE: Compartmental load-sensing technology has been used in the attempt to achieve optimal soft tissue balance during total knee arthroplasty (TKA). This study was conducted to investigate the validity of such use of intraoperative sensing technology. METHODS: Ninety-three knees scheduled to undergo total knee arthroplasty for knee osteoarthritis with a tibial sensor were prospectively enrolled. Measurements were divided into three groups according to the three different time points of intraoperative load testing: group Trial (with the trial components), group Final (with the definitive cemented implants and an open joint capsule), and group Closed (with the definitive cemented implants and a closed joint capsule). Load measurements and component rotational alignments were documented at 10°, 30°, 45°, 90°, and 120° of flexion for all three groups, and compared. One year postoperatively, the joint line obliquity angle was obtained radiographically in the valgus and varus stress views at 10° and 30° flexion to evaluate the clinical instability. The Knee Society, Hospital for Special Surgery, and Western Ontario McMaster Universities Osteoarthritis Index scores were used to determine functional outcomes. The correlations of the above outcomes with intraoperative load were evaluated. RESULTS: There were significant differences in medial and lateral loads at all flexion angles (except at a 120° lateral load) between group Trial and group Final (p < 0.05). Tibial trays were internally rotated to a significantly higher degree in group Final than in group Trial (p = 0.010). The lateral compartmental load significantly decreased after patellar inversion (p = 0.037). There were no correlations of intraoperative load with clinical instability and functional outcomes. CONCLUSION: Significant variability was observed between the trial and final implant measurements and intraoperative sensing data were not correlated with instability or functional outcomes over a 1-year period. Therefore, intraoperative sensor technology provides limited feedback and clinical efficacy in the adjustment of the soft tissue balance during TKA. LEVEL OF EVIDENCE: Level II.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Rango del Movimiento Articular
4.
Knee Surg Sports Traumatol Arthrosc ; 29(10): 3409-3417, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32869124

RESUMEN

PURPOSE: This study aimed to evaluate the optimal dosage of topical tranexamic acid (TXA) considering the efficacy and safety for controlling bleeding after total knee arthroplasty (TKA). METHODS: This prospective randomized double-blinded placebo-controlled comparative study included 325 patients scheduled to undergo TKA, who were randomly assigned to five groups based on the topical TXA injection (n = 65 per group): control; group 1, 0.5 g TXA; group 2, 1.0 g TXA; group 3, 2.0 g TXA; and group 4, 3.0 g TXA. The primary outcome was decrease in postoperative hemoglobin levels. The secondary outcomes were blood loss calculated using Good's method, drainage volume, frequency of transfusion, and range of motion (ROM). Plasma TXA levels and complications were also evaluated. RESULTS: Significant differences were noted in the decrease in hemoglobin levels between the control group and groups 2 (p = 0.0027), 3 (p = 0.005), and 4 (p = 0.001). No significant differences were shown among the experimental groups. Significant differences in total blood loss and frequency of transfusion were noted between the control group and groups 2 (p = 0.004, 0.002, respectively), 3 (p = 0.007, 0.001, respectively), and 4 (p = 0.001, 0.009, respectively) without showing significant differences among the experimental groups. With respect to drainage volume, no significant differences were observed among the groups. The serum TXA levels increased proportionally with the applied dose of topical TXA immediately and at 3 and 6 h postoperatively. Symptomatic deep vein thrombosis or pulmonary embolism was not observed in any group. Other complications related to TXA administration were not detected. CONCLUSION: Topical application of 1.0 g or more of TXA shows significant bleeding control without a dose-response relationship. Blood TXA levels increase with the TXA dose following topical TXA application. Therefore, to prevent overdosing and reduce potential complications with ensuring the effectiveness, 1.0 g of TXA is recommended as a topical application. LEVEL OF EVIDENCE: I.


Asunto(s)
Antifibrinolíticos , Artroplastia de Reemplazo de Rodilla , Ácido Tranexámico , Administración Intravenosa , Administración Tópica , Pérdida de Sangre Quirúrgica/prevención & control , Humanos , Hemorragia Posoperatoria/prevención & control , Estudios Prospectivos
5.
J Arthroplasty ; 36(4): 1302-1309, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33349499

RESUMEN

BACKGROUND: Lighter weight and lower modulus are potential advantages of titanium (Ti) implants over cobalt chrome (CoCr) implants in total knee arthroplasty (TKA). This study was conducted to determine whether Ti implants in TKA resulted in better clinical outcomes and radiologic results. METHODS: One hundred and eight patients (216 knees) with knee arthritis warranting bilateral primary TKA were randomly allocated to undergo Ti rotating-platform TKA in one knee and CoCr rotating-platform TKA in the contralateral knee. The mean follow-up period was 5.3 years (range, 1-7 years). The weight of Ti implants was one-third lighter than that of CoCr implants (133.9 g vs 390.1 g, P < .01). Clinical outcomes were evaluated using clinical scores, patient preferences (lightness, comfort, naturalness, and satisfaction), gait analysis (kinetic and kinematic data), range of motion, and degree of pain. Radiologic results were evaluated based on the radiolucent line (RLL), degree of medial tibial bone loss, and loosening as seen on X-ray. RESULTS: No significant differences were observed in clinical scores or patient preference. Regarding implant weight, approximately 70% of patients did not perceive the Ti implant as lighter. No significant differences were observed in gait analysis, range of motion, or degree of pain. The RLL was seen in 9% of the Ti implant group and 19% of the CoCr implant group. CONCLUSION: The lighter Ti implant did not show any clinical benefit over CoCr implants. The lightness of the Ti implant is not sufficient to matter or be noticeable. However, the Ti implant showed lower rate of RLL than the CoCr implant. LEVEL OF EVIDENCE: level I, randomized controlled trial.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Rango del Movimiento Articular , Titanio
6.
J Korean Med Sci ; 35(38): e315, 2020 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-32989928

RESUMEN

BACKGROUND: Demographic change and advances in technology affect transurethral surgery and outpatient procedures in the urologic field. There are few population-based studies that accurately assess the trend of transurethral surgery and outpatient procedures including diagnostic tests. We investigated the recent epidemiologic trends in transurethral surgeries and urological outpatient procedures from 2009 to 2016 in Korea using the entire population-based cohort. METHODS: We analyzed medical service claim data of transurethral surgery, urological outpatient procedures submitted by medical service providers from the Health Insurance Review and Assessment Service from 2009 to 2016. RESULTS: Transurethral ureter surgery increased by 134.9% from 14,635 in 2009 to 34,382 in 2016 (B = 2,698; R² = 0.98; P < 0.001). The transurethral bladder surgery increased by 65.5% from 12,482 in 2009 to 20,658 in 2016 (B = 1,149; R² = 0.97; P < 0.001). Over the 8-years period, there were not significant changes in transurethral prostate (B = 43; R² = 0.04; P = 0.617) and urethral surgery (B =-12; R² = 0.18; P = 0.289). The significantly increasing trends in cystoscopy (B = 5,260; R² = 0.95; P < 0.001) and uroflowmetry (B = 53,942; R² = 0.99; P < 0.001) were observed during the 8-year period. There was no difference in bladder catheterization during the 8-year period. Urodynamic study (UDS: B =-2,156; R² = 0.77; P = 0.003) and electrical stimulation treatment (EST: B =-1,034; R² = 0.87; P < 0.001) significantly decreased. CONCLUSION: In Korea, transurethral ureter surgery and transurethral bladder surgery have been continuously increasing. Transurethral prostate surgery and transurethral urethral surgery remained constant with no increase or decrease. Cystoscopy and uroflowmetry continue to increase, while UDS and EST continue to decrease.


Asunto(s)
Síntomas del Sistema Urinario Inferior/cirugía , Procedimientos Quirúrgicos Urológicos/tendencias , Anciano , Estudios de Cohortes , Estudios Transversales , Cistoscopía/tendencias , Bases de Datos Factuales , Estimulación Eléctrica , Humanos , Síntomas del Sistema Urinario Inferior/patología , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , República de Corea , Urodinámica
7.
Knee Surg Sports Traumatol Arthrosc ; 28(9): 2980-2989, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31559465

RESUMEN

PURPOSE: Recently, the Persona total knee arthroplasty (TKA) system with more anatomical features and a similarly high flexion to the previous version, LPS-Flex, was introduced and is widely used. This study aimed to compare the early outcomes obtained using Persona versus an LPS-Flex fixed PS implant. METHODS: A total of 784 knees that underwent primary TKAs (162: Persona group and 622: LPS-Flex group) were included. After 1:2 propensity score matching, there were 143 and 286 knees in Persona and LPS-Flex groups, respectively. Range of motion at the 2-year follow-up was the primary variable. Secondary variables were functional score, ability to perform activities requiring deep knee flexion, patient satisfaction, and radiographic measurements, including radiolucent line (RLL). RESULTS: The average postoperative maximal flexion measured by goniometer at 2 years after TKA was 126.1° ± 10.8° (range 95°-140°) for the Persona group and 132.7° ± 11.7° (range 103°-145°) for the LPS-Flex group (P < 0.05). This significant difference was observed from 1 year postoperatively (P < 0.05). The two groups did not show a significant difference in functional score, postoperative ability in high flexion activities, and satisfaction at the 2-year follow-up. The rate of RLL was significantly lower in the Persona group (P < 0.05). CONCLUSION: At the 2-year follow-up, the Persona group had less maximal flexion; however, the difference in flexion did not seem to affect clinical outcomes. According to the radiological results, the Persona system shows less RLL than does the LPS-Flex system. LEVEL OF EVIDENCE: III.


Asunto(s)
Artroplastia de Reemplazo de Rodilla/instrumentación , Prótesis de la Rodilla , Diseño de Prótesis , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Análisis por Apareamiento , Medición de Resultados Informados por el Paciente , Satisfacción del Paciente , Rango del Movimiento Articular , Estudios Retrospectivos
8.
J Arthroplasty ; 35(1): 69-75, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31563397

RESUMEN

BACKGROUND: Systemic steroid has been used to control pain and nausea in total knee arthroplasty (TKA), but most studies recommend a single dose administration prior to, or during, surgery. This study aimed to determine the efficacy of administration on 1 day postoperatively. METHODS: Patients who were scheduled to undergo TKA were randomly assigned to the following groups: control group, receiving normal saline injection; group 1, receiving 10 mg dexamethasone intravenously (IV) 1 hour before surgery; group 2, receiving 0.1 mg/kg dexamethasone (IV) 24 hours after surgery; or group 3, receiving 0.2 mg/kg dexamethasone (IV) 24 hours after surgery (n = 44-46 per group). Primary outcomes were pain and nausea visual analogue scale (VAS). Secondary outcomes were analgesic administration, rescue antiemetic administration, C-reactive protein, range of motion, and complications. RESULTS: Postoperative pain and nausea remained high for 48 hours post-TKA. Group 1 had lower pain and nausea VAS scores than did the control group (P < .01) for only 24 hours post-TKA. Groups 2 and 3 had lower pain and nausea VAS scores than did the control group and group 1 (P < .01) 48 hours post-TKA. Analgesic and antiemetic administration were significantly lower in groups 2 and 3 than in the control group during 48 hours after TKA. There were no differences in C-reactive protein level and range of motion, and complications were not detected. CONCLUSION: The effect of preoperative and postoperative administration of dexamethasone for controlling pain and nausea was observed only for 24 hours. Considering that severe pain and nausea persisted for more than 48 hours after TKA, additional administration of dexamethasone at 1 day postoperatively is suggested. LEVEL OF EVIDENCE: Level I.


Asunto(s)
Antieméticos , Artroplastia de Reemplazo de Rodilla , Antieméticos/uso terapéutico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Dexametasona/uso terapéutico , Método Doble Ciego , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/etiología , Náusea y Vómito Posoperatorios/prevención & control
9.
Int J Urol ; 26(5): 558-564, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30803067

RESUMEN

OBJECTIVES: To provide surgical treatment trends for urinary stone disease in Korea. METHODS: We analyzed medical service claim data of surgical treatments to urinary stone disease submitted by medical service providers from the Health Insurance Review and Assessment Service from 2009 to 2016. RESULTS: There was a significantly increasing trend among outpatients and inpatients for urinary stone disease from 2009 to 2016 (R2  = 0.643, P = 0.017; R2  = 0.575, P = 0.029). The number of shock wave lithotripsy for treating urinary stone disease increased by 16% from 89 553 in 2009 to 104 013 in 2016 (R2  = 0.684). The number of ureteroscopic lithotripsy increased by 97% from 6106 in 2009 to 12 057 in 2016 (R2  = 0.99). The number of flexible ureteroscopic lithotripsy increased by 16-fold from 219 in 2009 to 3712 in 2016 (R2  = 0.756). The number of percutaneous nephrolithotomy increased by 99.7% from 919 in 2009 to 1835 in 2016 (R2  = 0.987). The use of non-contrast and contrast-enhanced computed tomography in the diagnostic codes for urinary stone disease increased by 394.8% and 263.3% from 2009 to 2016, respectively (R2  = 0.83; R2  = 0.967). Conversely, the use of intravenous pyelography decreased 26.2% over the same period (R2  = 0.945). CONCLUSIONS: Outpatient and inpatient procedures for urinary stone disease have increased over the past 8 years in Korea. Shock wave lithotripsy is the most widely used treatment modality for urinary stone disease, and endoscopic surgical procedures are rapidly being implemented. There has been a steep increase in the use of computed tomography, whereas conventional intravenous pyelography is declining.


Asunto(s)
Litotricia/tendencias , Nefrolitotomía Percutánea/tendencias , Ureteroscopía/tendencias , Urolitiasis/epidemiología , Urolitiasis/terapia , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , República de Corea/epidemiología , Resultado del Tratamiento
10.
J Urol ; 200(6): 1371-1377, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30036513

RESUMEN

PURPOSE: The aim of this study was to develop and validate a decision support model using a machine learning algorithm to predict treatment success after single session shock wave lithotripsy in ureteral stone cases. MATERIALS AND METHODS: Of the 1,803 patients treated with shock wave lithotripsy we selected those with ureteral stones who had preoperative computerized tomography available. Treatment success after single session shock wave lithotripsy was defined as freedom from stones or residual stone fragments less than 2 mm long on computerized tomography or plain x-ray of the kidneys, ureters and bladder 2 weeks later. Decision tree analysis was done using a machine learning algorithm to identify relevant parameters. A decision support model was developed to calculate the probability of treatment success. RESULTS: A total of 791 patients were enrolled in study. Mean ± SD stone length was 5.9 ± 2.3 mm and mean stone volume was 89.3 ± 140.0 mm3. The overall treatment success rate after SWL was 64.4% (509 cases). The rate for upper, middle and lower ureter stones was 59.8%, 65.5% and 69.6%, respectively. On decision tree analysis the top 3 performance criteria factors were volume, length and HU. Decision models were constructed with all possible combinations of factors. The model with 15 factors had greater than 92% accuracy and an average ROC AUC of 0.951. CONCLUSIONS: We applied a machine learning algorithm, a subfield of artificial intelligence, to predict the outcome after single session shock wave lithotripsy for ureteral stones. A 92.29% accurate decision model was developed with 15 factors and an average ROC AUC of 0.951.


Asunto(s)
Litotricia , Aprendizaje Automático , Cálculos Ureterales/cirugía , Adulto , Algoritmos , Simulación por Computador , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Cálculos Ureterales/diagnóstico por imagen
11.
World J Urol ; 36(8): 1299-1306, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29549483

RESUMEN

PURPOSE: We compared the outcomes of SWL to treat distal ureter stones with regard to the conventional prone and supine positions using the transgluteal approach through the greater sciatic foramen. METHODS: A prospective, randomized, single-blind, and multicenter study was conducted between October 2014 and July 2015. The inclusion criteria were radio-opaque distal ureter stones with a maximum diameter of 0.5-2 cm as measured on a CT scan. The included 160 patients were randomly assigned to two groups: the prone group (n = 80; treated in the conventional prone position) and the transgluteal group (n = 80; treated in the supine position using a transgluteal approach). In the latter group, the focused shock wave was transmitted through the greater sciatic foramen with the head positioned at a 40° angle to the vertical. "Stone-free" was defined as the complete clearance of stone fragments, assessed using a CT scan at 2 weeks after treatment. Overall satisfaction was self-reported using a 0-5 Likert scale. RESULTS: The overall efficacy was 66.9%. The stone-free rate was significantly higher in the transgluteal group (72.6%) than in the prone group (54.7%; odds ratio 2.413, 95% CI 1.010-5.761, P = 0.023). No serious adverse events due to treatment were observed in either group. The satisfaction score of the transgluteal group was 4.21 ± 0.81, and 83.6% were willing to repeat the same procedure if necessary. CONCLUSIONS: SWL using the transgluteal approach via a supine position through the greater sciatic foramen was more effective than via the conventional prone position. Furthermore, this approach provided a comparably safe and satisfactory procedure.


Asunto(s)
Litotricia/métodos , Posicionamiento del Paciente/métodos , Cálculos Ureterales/terapia , Adolescente , Adulto , Nalgas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Posición Prona , Estudios Prospectivos , Método Simple Ciego , Posición Supina , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Cálculos Ureterales/diagnóstico por imagen , Adulto Joven
12.
World J Urol ; 36(8): 1307, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29644410

RESUMEN

The funding number was incorrect in the original published article. The correct funding number should read as follows.

13.
Korean J Physiol Pharmacol ; 21(6): 599-607, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29200902

RESUMEN

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

14.
Circ Res ; 114(7): 1133-43, 2014 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-24526703

RESUMEN

RATIONALE: Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear. OBJECTIVE: Recently, we suggested that casein kinase 2α1-dependent phosphorylation of HDAC2 leads to enzymatic activation, which in turn induces cardiac hypertrophy. Here we report an alternative post-translational activation mechanism of HDAC2 that involves acetylation of HDAC2 mediated by p300/CBP-associated factor/HDAC5. METHODS AND RESULTS: Hdac2 was acetylated in response to hypertrophic stresses in both cardiomyocytes and a mouse model. Acetylation was reduced by a histone acetyltransferase inhibitor but was increased by a nonspecific HDAC inhibitor. The enzymatic activity of Hdac2 was positively correlated with its acetylation status. p300/CBP-associated factor bound to Hdac2 and induced acetylation. The HDAC2 K75 residue was responsible for hypertrophic stress-induced acetylation. The acetylation-resistant Hdac2 K75R showed a significant decrease in phosphorylation on S394, which led to the loss of intrinsic activity. Hdac5, one of class IIa HDACs, directly deacetylated Hdac2. Acetylation of Hdac2 was increased in Hdac5-null mice. When an acetylation-mimicking mutant of Hdac2 was infected into cardiomyocytes, the antihypertrophic effect of either nuclear tethering of Hdac5 with leptomycin B or Hdac5 overexpression was reduced. CONCLUSIONS: Taken together, our results suggest a novel mechanism by which the balance of HDAC2 acetylation is regulated by p300/CBP-associated factor and HDAC5 in the development of cardiac hypertrophy.


Asunto(s)
Cardiomegalia/metabolismo , Histona Desacetilasas/metabolismo , Factores de Transcripción p300-CBP/metabolismo , Acetilación , Animales , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/genética , Ratones , Mutación , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/metabolismo , Fosforilación , Ratas , Ratas Sprague-Dawley , Factores de Transcripción p300-CBP/genética
15.
J Hand Surg Am ; 41(10): e331-e335, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27546444

RESUMEN

PURPOSE: To compare the efficacy of corticosteroid injections in treating trigger finger in patients with and without metabolic syndrome (MS). METHODS: Fifty-one patients with trigger finger and MS were matched for age and sex with 52 control patients without MS. All patients were treated with a single corticosteroid injection. The response to treatment, including objective triggering, tenderness at the A1 pulley, and Quick Disabilities of the Arm, Shoulder, and Hand score (QuickDASH) were assessed at 6, 12, and 24 weeks' follow-up. Before the 24-week evaluation, 7 in the MS group and 10 in the control group were lost to follow-up. RESULTS: Prior to treatment, patients with MS had Quinnell grades and initial mean QuickDASH scores similar to those in the control group. The proportion of treatment failure for the MS group (49%) was significantly higher than that of control group (19%) after 6 months' follow-up. Unresolved triggering was more prevalent in patients in the MS group at the 12- and 24-week follow-ups. Local tenderness was more persistent in the MS group than in the control group throughout the 24 weeks of follow-up. After 24 weeks of follow-up, 14 patients (27%) in the MS group and 6 (12%) in the control group underwent surgical release. QuickDASH scores of the MS group were worse than those of the control group at the 12- and 24-week follow-ups. CONCLUSIONS: Trigger finger patients with MS are at risk of poorer functional outcomes and treatment failure after a single corticosteroid injection than age- and sex-matched controls. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.


Asunto(s)
Corticoesteroides/uso terapéutico , Síndrome Metabólico/epidemiología , Rango del Movimiento Articular/fisiología , Trastorno del Dedo en Gatillo/tratamiento farmacológico , Trastorno del Dedo en Gatillo/epidemiología , Adulto , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Inyecciones Intralesiones , Masculino , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Dimensión del Dolor/efectos de los fármacos , Rango del Movimiento Articular/efectos de los fármacos , Valores de Referencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Insuficiencia del Tratamiento , Trastorno del Dedo en Gatillo/diagnóstico
16.
Alcohol Clin Exp Res ; 38(6): 1502-9, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24797321

RESUMEN

BACKGROUND: It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. METHODS: In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. RESULTS: In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. CONCLUSIONS: Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results suggest that higher blood EtOH and acetaldehyde concentrations in ADH1B*2/*2 may constitute the mechanism of protection against alcoholism by ADH1B*2/*2.


Asunto(s)
Alcohol Deshidrogenasa/genética , Etanol/farmacocinética , Acetaldehído/sangre , Adulto , Alcohol Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa/genética , Aldehído Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa Mitocondrial , Alelos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Etanol/administración & dosificación , Etanol/sangre , Genotipo , Humanos , Masculino , Adulto Joven
17.
Clin Orthop Surg ; 16(3): 405-412, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827759

RESUMEN

Background: The etiology and pathology of mucoid degeneration of the anterior cruciate ligament (MD-ACL) remain poorly understood. MD-ACL may be associated with knee osteoarthritis (OA) or a mechanism other than OA. This study evaluated the radiological differences between knees with MD-ACL and those with a normal ACL and compared the clinical and radiological features of knees with MD-ACL according to the knee OA status. Methods: This retrospective study compared the radiological features of the intercondylar notch width index (NWI) and posterior tibial slope (PTS) of 67 MD-ACL patients (MD group) and 67 age-, sex-, and OA grade-matched patients with a normal ACL (control group). During the subgroup analysis, MD-ACL patients were divided into the non-OA subgroup (n = 41) and OA subgroup (n = 26). The pain location and characteristics of the knee, PTS, and NWI were compared between these subgroups. Results: Compared to the control group, the MD group had a lower NWI (0.26 ± 0.03 vs. 0.28 ± 0.01, p < 0.001) and a larger PTS (11.3° ± 3.0° vs. 9.2° ± 2.5°, p < 0.001). During the subgroup analysis, the most common pain locations were the posterior and medial aspects of the knee in the non-OA subgroup (43.9%) and OA subgroup (53.8%), respectively. Pain on terminal flexion was the most common pain characteristic in both subgroups (non-OA subgroup, 73.1%; OA subgroup, 53.8%). The PTS was not different between subgroups (11.7° ± 3.2° in the non-OA subgroup vs. 10.6° ± 2.7° in the OA subgroup; p = 0.159). However, the non-OA subgroup had a lower NWI than the OA subgroup (0.25 ± 0.03 vs. 0.28 ± 0.02, p = 0.001). Conclusions: Patients with MD-ACL had a lower NWI and a larger PTS than patients with a normal ACL. Furthermore, the clinical and radiological features of MD-ACL differed according to the knee OA status. A narrow intercondylar notch may be more closely associated with the development of MD-ACL without OA.


Asunto(s)
Ligamento Cruzado Anterior , Osteoartritis de la Rodilla , Radiografía , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/patología , Persona de Mediana Edad , Adulto , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Anciano
18.
Knee Surg Relat Res ; 36(1): 4, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38217058

RESUMEN

BACKGROUND: Achieving consistent accuracy in radiographic measurements across different equipment and protocols is challenging. This study evaluates an advanced deep learning (DL) model, building upon a precursor, for its proficiency in generating uniform and precise alignment measurements in full-leg radiographs irrespective of institutional imaging differences. METHODS: The enhanced DL model was trained on over 10,000 radiographs. Utilizing a segmented approach, it separately identified and evaluated regions of interest (ROIs) for the hip, knee, and ankle, subsequently integrating these regions. For external validation, 300 datasets from three distinct institutes with varied imaging protocols and equipment were employed. The study measured seven radiologic parameters: hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, joint line convergence angle, weight-bearing line ratio, joint line obliquity angle, and lateral distal tibial angle. Measurements by the model were compared with an orthopedic specialist's evaluations using inter-observer and intra-observer intraclass correlation coefficients (ICCs). Additionally, the absolute error percentage in alignment measurements was assessed, and the processing duration for radiograph evaluation was recorded. RESULTS: The DL model exhibited excellent performance, achieving an inter-observer ICC between 0.936 and 0.997, on par with an orthopedic specialist, and an intra-observer ICC of 1.000. The model's consistency was robust across different institutional imaging protocols. Its accuracy was particularly notable in measuring the hip-knee-ankle angle, with no instances of absolute error exceeding 1.5 degrees. The enhanced model significantly improved processing speed, reducing the time by 30-fold from an initial 10-11 s to 300 ms. CONCLUSIONS: The enhanced DL model demonstrated its ability for accurate, rapid alignment measurements in full-leg radiographs, regardless of protocol variations, signifying its potential for broad clinical and research applicability.

19.
J Spinal Cord Med ; : 1-7, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37982995

RESUMEN

OBJECTIVE: To compare the effects of intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) on spinal cord injury-related neuropathic pain with sham controls, using neuropathic pain-specific evaluation tools. DESIGN: A randomized, double-blind, sham-controlled trial. SETTING: Rehabilitation medicine department of a university hospital. PARTICIPANTS: Thirty-three patients with spinal cord injury-related neuropathic pain. INTERVENTIONS: Patients were randomly allocated to one of three groups (real iTBS, real rTMS, and sham rTMS). Each patient underwent five sessions of assigned stimulation. OUTCOME MEASURES: Before and after completion of the five sessions, patients were evaluated using the self-completed Leeds Assessment of Neuropathic Symptoms and Signs, Numeric Rating Scale, Neuropathic Pain Symptom Inventory, and Neuropathic Pain Scale. RESULTS: Real iTBS and real rTMS reduced pain levels after stimulation according to all the evaluation tools, and the changes were significant when compared to the values of the sham rTMS group. No significant differences were found between the real iTBS and real rTMS groups. CONCLUSION: Both iTBS and rTMS were effective in reducing spinal cord injury-related neuropathic pain. When safety, convenience, and compliance are considered, iTBS would have an advantage over rTMS in clinical situations with spinal cord injury-related neuropathic pain.Trial Registration: This trial was registered with the Clinical Research Information Service (registration no. KCT0004976).

20.
Investig Clin Urol ; 64(1): 91-101, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36629070

RESUMEN

PURPOSE: We evaluated the performance of a new multi-degree-of-freedom articulating laparoscopic instrument, ArtiSential, and compared it with that of a straight-shaped instrument and the da Vinci surgical system, in renal surgery using porcine model. MATERIALS AND METHODS: Nine female Yorkshire pigs were equally divided into three groups. The three groups were compared at each surgical step in terms of objective and subjective parameters. RESULTS: The median operative times for renal pedicle clamping and ureter dissection were significantly shorter in ArtiSential group than robotic group (1.3 min vs. 4.7 min, p=0.002; 8.1 min vs. 11.1 min, p=0.015). The median operative time for bladder repair was significantly longer in ArtiSential group than robotic and straight-shaped groups (17.9 min vs. 5.5 min, p=0.002; 17.9 min vs. 9.3 min, p=0.026). There were no significant differences among groups in terms of blood loss or intraoperative complications. ArtiSential device was less useable for renorrhaphy (p=0.009) and bladder repair (p=0.002) compared to the robotic system. ArtiSential group was less accurate than robotic group in terms of tumor resection, renorrhaphy, and bladder repair. During ureter dissection, bladder cuff excision, and bladder repair, the surgeon experienced greater wrist discomfort but lesser back discomfort in ArtiSential group than robotic group. CONCLUSIONS: For most steps, ArtiSential performed as well as robotic and straight-shaped instruments. The development of specialized surgical techniques for ArtiSential will maximize the advantages of these instruments.


Asunto(s)
Riñón , Laparoscopía , Animales , Femenino , Riñón/cirugía , Laparoscopía/efectos adversos , Laparoscopía/instrumentación , Robótica , Porcinos , Uréter/cirugía , Procedimientos Quirúrgicos Urológicos/efectos adversos , Procedimientos Quirúrgicos Urológicos/instrumentación , Modelos Animales , Tempo Operativo , Resultado del Tratamiento
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