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Alkaline polymer electrolytes (APEs) are essential materials for alkaline energy conversion devices such as anion exchange membrane fuel cells (AEMFCs) and water electrolyzers (AEMWEs). Here, we report a series of branched poly(aryl-co-aryl piperidinium) with different branching agents (triptycene: highly-rigid, three-dimensional structure; triphenylbenzene: planar, two-dimensional structure) for high-performance APEs. Among them, triptycene branched APEs showed excellent hydroxide conductivity (193.5â mS cm-1 @80 °C), alkaline stability, mechanical properties, and dimensional stability due to the formation of branched network structures, and increased free volume. AEMFCs based on triptycene-branched APEs reached promising peak power densities of 2.503 and 1.705â W cm-2 at 75/100 % and 30/30 % (anode/cathode) relative humidity, respectively. In addition, the fuel cells can run stably at a current density of 0.6â A cm-2 for 500â h with a low voltage decay rate of 46â µV h-1 . Importantly, the related AEMWE achieved unprecedented current densities of 16â A cm-2 and 14.17â A cm-2 (@2â V, 80 °C, 1â M NaOH) using precious and non-precious metal catalysts, respectively. Moreover, the AEMWE can be stably operated under 1.5â A cm-2 at 60 °C for 2000â h. The excellent results suggest that the triptycene-branched APEs are promising candidates for future AEMFC and AEMWE applications.
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BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.
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Linfoma no Hodgkin , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Humanos , Anticuerpos , Antígenos CD19 , Epítopos/metabolismo , Inmunoterapia Adoptiva/efectos adversos , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Receptores Quiméricos de Antígenos/metabolismo , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidoresRESUMEN
Factors associated with tendon degeneration have not been fully investigated. The purpose of this study was to identify factors associated with tendon degeneration in patients with rotator cuff tear. A total of 93 patients with a full-thickness rotator cuff tear (fRCT) were included in the study. A full-thickness supraspinatus tendon sample was harvested from the middle portion between the lateral edge and the musculotendinous junction, and assessed histologically. Association between the degree of tendon degeneration and factors in demographic, clinical, radiologic, and arthroscopic categories were investigated. The mean of the total degeneration score was significantly lower in patients with symptom duration of 6 months or less than longer than 6 months (13.1 ± 2.6 vs 14.4 ± 2.3, p = 0.010). This study showed that tendon degeneration significantly progressed 6 months after the onset of symptoms, and suggested early intervention to avoid further deterioration of tendon degeneration.
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Lesiones del Manguito de los Rotadores/fisiopatología , Manguito de los Rotadores/fisiopatología , Traumatismos de los Tendones/fisiopatología , Anciano , Artroscopía , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/cirugía , Traumatismos de los Tendones/cirugíaRESUMEN
PURPOSE: To compare union rates and clinical and radiologic outcomes after arthroscopic and open bone grafting and internal fixation for unstable scaphoid nonunions. METHODS: Between March 2009 and November 2014, patients with unstable scaphoid nonunion underwent arthroscopic (group A) or open (group O) bone grafting and internal fixation. One senior surgeon alternatively performed either arthroscopic or open osteosynthesis for the same surgical indications. Visual analog scale score, grip strength, active range of motion, Mayo wrist score (MWS), and Disabilities of Arm, Shoulder, and Hand score were assessed preoperatively and postoperatively. Union was determined by computed tomography 8 to 10 weeks postoperatively with bridging trabecula at the nonunion site. Scapholunate angle (SLA), radiolunate angle (RLA), and lateral intrascaphoid angle (LISA), plus height/length ratio (HLR) served to gauge carpal bone alignment in preoperative and postoperative radiographs. Those outcomes of patients with carpal collapse deformities, who met following conditions; (1) LISA of >45° or HLR of >0.65 on computed tomography images or (2) SLA of >60° or RLA of >10° on plain radiographs, were also compared. RESULTS: Overall, 62 patients qualified for study (group A, 28; group O, 34). Union rates did not differ by patient subset (group A, 96.4%; group O, 97.1%; P â 1); and visual analog scale score, grip strength, range of motion, Mayo Wrist Score, and Disabilities of Arm, Shoulder, and Hand scores were similar at last follow-up. In radiographic assessments, SLA, RLA, and LISA were similar, whereas scaphoid HLR excelled through open technique (group A, 0.59 ± 0.07; group O, 0.55 ± 0.05; P = .002). Subgroup analysis of patients with carpal collapse deformities (group A, 9; group O, 14) showed that all radiographic measures in group A (vs group O) reflected lesser correction (SLA, 56.7° ± 7.3° vs 49.2°±9.1° [P = .049]; RLA, 9.2° ± 2.0° vs 5.7° ± 3.0° [P = .005]; LISA, 34.8° ± 4.8° vs 25.6° ± 13.0° [P = .028]; HLR, 0.66 ± 0.04 vs 0.54 ± 0.07 [P < .001]). CONCLUSIONS: Arthroscopic and open bone grafting and internal fixation in treating unstable scaphoid nonunions, did not show any significant differences in clinical and radiologic outcomes at the minimum of 2 years after operation. In scaphoid nonunions with carpal collapse deformities, open bone grafting restored better carpal alignment than arthroscopic bone grafting, although there were no differences in clinical outcomes between the 2 techniques. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Artroscopía/métodos , Trasplante Óseo/métodos , Fijación Interna de Fracturas/métodos , Fracturas no Consolidadas/cirugía , Hueso Escafoides/lesiones , Hueso Escafoides/cirugía , Adulto , Femenino , Fracturas no Consolidadas/diagnóstico por imagen , Fracturas no Consolidadas/fisiopatología , Fuerza de la Mano/fisiología , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio , Rango del Movimiento Articular/fisiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Articulación de la Muñeca/cirugía , Adulto JovenRESUMEN
BACKGROUND: In the setting of periprosthetic humeral fractures, the humeral stem of the implant represents a substantial challenge to the optimal method of proximal fixation. This study aimed to compare the initial biomechanical stability provided by cerclage cables with a locking plate insert versus bicortical locking screws (i.e., the gold standard for fixation) in fresh cadaveric humeri. METHODS: After calculating the sample size, we utilized 10 sets of cadaveric specimens and created a 5-mm osteotomy gap 120 mm distal to the tip of the greater tuberosity, simulating a Wright and Cofield type-B periprosthetic humeral fracture on each specimen. Using 3 locking screws for distal fragment fixation, identical in all specimens, the specimens were assigned to Group A (3 cerclage cables with a plate insert) or Group B (3 locking bicortical screws) for proximal fragment fixation. Biomechanical tests included stiffness in varus and valgus bending, torsion, and axial compression, and a single load to failure. RESULTS: No significant differences were observed in the biomechanical metrics between the 2 groups. CONCLUSIONS: Our study revealed that fixation with use of cerclage cables with a plate insert demonstrated biomechanical stability comparable with that of bicortical locking screw fixation when addressing the proximal fragment in Wright and Cofield type-B periprosthetic humeral fractures. CLINICAL RELEVANCE: For proximal fragment fixation of periprosthetic humeral fractures, cerclage cables with a plate insert can be utilized as an effective fixation method that offers initial fixation strength that is comparable to the use of 3 locking bicortical screws.
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Placas Óseas , Tornillos Óseos , Cadáver , Fijación Interna de Fracturas , Fracturas Periprotésicas , Humanos , Fracturas Periprotésicas/cirugía , Fracturas Periprotésicas/etiología , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/efectos adversos , Fenómenos Biomecánicos , Anciano , Femenino , Masculino , Fracturas del Húmero/cirugía , Anciano de 80 o más AñosRESUMEN
Objective: Advancements in surgical techniques for cerebral arteriovenous malformation (AVM) underscore its efficacy. Our research aims to showcase the positive outcomes of treating low-grade AVMs surgically, focusing on safety and effectiveness. Methods: We retrospectively reviewed 55 patients (36 males, 19 females, and average age 37.4 years) with Spetzler-Martin (S-M) grade 1 and 2 AVMs who underwent surgical resection between January 2009 and December 2022. Results: In our study, 55 patients with S-M grade 1 and 2 AVMs underwent surgical resection, evenly divided between grades 1 (50.9%) and 2 (49.1%). Intracranial hemorrhage was the primary symptom in 74.5% of cases. Pre-operative Glasgow Coma Scale (GCS) scores revealed 69.1% of patients scored above 13, with 18% below 8. Successful resection was achieved in 87.3%. Postoperatively, 95.5% of ruptured and 90.9% of unruptured AVM patients showed lower or same modified Rankin Scale scores. Poorer outcomes were significantly linked to lower GCS scores and intranidal/flow-related aneurysms through multivariate logistic regression. Postoperative seizures noted in 9 patients, were exclusive to the ruptured AVM group. Conclusion: Our findings indicate surgical resection as a beneficial treatment for low-grade AVMs, yielding high cure rates and positive functional outcomes in both ruptured and unruptured cases. Preoperative GCS scores and the presence of associated aneurysms are predictive of postoperative functional status. Additionally, managing postoperative seizures effectively is key to enhancing prognosis.
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STAT3 regulates CD4+ T cell survival and differentiation. However, its effects on CD8+ T cells are not well understood. Here, we show that in comparison to WT CD8+ T cells, STAT3-deficient CD8+ T cells exhibit a preactivated memory-like phenotype, produce more IL-2, proliferate faster, and are more sensitive to activation-induced cell death (AICD). The enhanced proliferation and sensitivity to AICD correlated with downregulation of class-O forkhead transcription factors (FoxO1, FoxO3A), p21(waf1), p27(KIP1), Bcl-2, OX-40, and upregulation of FasL, Bax, and Bad. We examined whether STAT3-deficient CD8+ T cells can mount effective response during herpes simplex virus (HSV-1) infection and experimental autoimmune uveitis (EAU). Compared to WT mice, HSV-1-infected STAT3-deficient mice (STAT3KO) produced less IFN-γ and virus-specific KLRG-1+ CD8+ T cells. STAT3KO mice are also resistant to EAU and produced less IL-17-producing Tc17 cells. Resistance of STAT3KO to EAU correlated with marked expansion of IL-10-producing regulatory CD8+ T cells (CD8-Treg) implicated in recovery from autoimmune encephalomyelitis. Thus, increases of IL-6-induced STAT3 activation observed during inflammation may inhibit expansion of CD8-Tregs, thereby impeding recovery from uveitis. These results suggest that STAT3 is a potential therapeutic target for upregulating CD8+ T cell-mediated responses to viruses and suggest the successful therapeutic targeting of STAT3 as treatment for uveitis, derived, in part, from promoting CD8-Treg expansion.
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Linfocitos T CD8-positivos/citología , Herpes Simple/metabolismo , Interleucina-10/metabolismo , Factor de Transcripción STAT3/genética , Uveítis/inmunología , Animales , Apoptosis , Enfermedades Autoinmunes/inmunología , Proliferación Celular , Separación Celular , Citometría de Flujo , Regulación de la Expresión Génica , Herpes Simple/virología , Herpesvirus Humano 1 , Inflamación , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Factor de Transcripción STAT3/metabolismo , Regulación hacia Arriba , Uveítis/virologíaRESUMEN
Precast concrete (PC) structures have many advantages, but their use in the construction of middle- to high-rise buildings is limited. The construction of PC structures requires skills in various operations such as transportation, assembly, lifting, and structural soundness. In particular, regarding the seismic design of PC structures, it is necessary to clearly evaluate whether they have the same structural performance and usability as integral RC (cast-in-place) structures. In this paper, an experimental study was conducted to investigate whether PC members can achieve a seismic performance equivalent to that of RC members in beam-column joints, which are representative moment-resisting frames. The main variables are the two types of structural systems (intermediate and special moment-resisting frames) and the design flexural strength ratio of the columns and beams. The experimental and analytical results showed that the seismic performance of the PC specimens was equivalent to that of the RC specimens in terms of strength, stiffness, energy dissipation, and strain distribution, except for the specimen with splice sleeve bond failure of the column reinforcement (poor filling of the internal mortar). In addition, the I series satisfied the present emulation evaluation criteria for special moment-resisting frames of PC structures, confirming the possibility of applying intermediate moment-resisting frames.
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Meningiomas are the most common benign brain tumors, and most of them originate from the dura mater. However, in some cases, they can originate from the choroid plexus, and they are rarely found in the posterior cranial fossa. A 63-year-old female patient presented with dizziness and swallowing difficulty and was found to have a homogeneously enhancing mass in the right posterior cranial fossa. Mass removal was performed through retrosigmoid suboccipital craniotomy, and the mass was confirmed to originate from the choroid plexus. The pathological diagnosis was meningothelial meningioma. The patient had temporary swallowing difficulty but recovered without any neurological sequelae. We report a rare case of a lower cerebellopontine angle meningioma without dural attachment originating from the choroid plexus of the foramen of Luschka.
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This study was conducted to investigate the effect of ground granulated blast furnace slag on the structural performance of precast concrete beams, evaluating the flexural, shear and bonding performance by using the replacement ratio of the ground granulated blast furnace slag as a variable. The design strength of the concrete was set at 45 MPa in consideration of the characteristics of precast concrete products, and the replacement ratio of the ground granulated blast furnace slag to replace cement was 30 to 70%. The experimental results showed that all specimens had similar behavioral characteristics regardless of the replacement ratio of the ground granulated blast furnace slag. Comparison of the prediction results obtained by ACI 318-19 and EC 2 showed that the mean flexural strength and shear strength were higher than 1.19 and 1.43, respectively, and the mean bond strength was 1.57, satisfying the required performance. Therefore, the experimental results showed that in using the ground granulated blast furnace slag as an admixture for precast concrete, the cement replacement ratio may be increased up to 70% without causing any problems in securing the structural performance. Summarizing the results of the present study, a ground granulated blast furnace slag replacement ratio of 50% or lower may be reasonably applied.
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Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC). Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.
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Anticuerpos Monoclonales/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Inmunoterapia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Anticuerpos Monoclonales/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patologíaRESUMEN
This study was conducted to evaluate the flexural performance of hollow core slabs (HCS) incorporating the effect of surface roughness. The HCSs are suitable for long span structures due to reduced self-weight. The specimens were HCS with topping concrete and the variables were cross sectional height and surface roughness. The tests were conducted on simply supported beams under four-point loads. The results showed that specimens with interface roughness applied in the lengthwise direction of members exhibited ductile flexural behavior up to peak load than those with interface roughness applied in the member width direction. Their flexural strength was also higher by 1-7% on average, indicating that they are advantageous in improving structural performance.
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OBJECTIVE: Carotid endarterectomy (CEA) is an effective surgical procedure for treating symptomatic or asymptomatic patients with carotid stenosis. Many neurosurgeons use a shunt to reduce perioperative ischemic complications. However, the use of shunting is still controversial, and the shunt procedure can cause several complications. In our institution, we used two types of modified arteriotomy suture techniques instead of using a shunt. METHODS: In technique 1, to prevent ischemic complications, we sutured a third of the arteriotomy site from both ends after removing the plaque. Afterward, the unsutured middle third was isolated from the arterial lumen by placing a curved Satinsky clamp. And then, we opened all the clamped carotid arteries before finishing the suture. In technique 2, we sutured the arteriotomy site at the common carotid artery (CCA). We then placed a curved Satinsky clamp crossing from the sutured site to the carotid bifurcation, isolating the unsutured site at the internal carotid artery (ICA). After placing the Satinsky clamp, the CCA and external carotid artery (ECA) were opened to allow blood flow from CCA to ECA. By opening the ECA, ECA collateral flow via ECA-ICA anastomoses could help to reduce cerebral ischemia. RESULTS: The modified suture methods can reduce the cerebral ischemia directly (technique 1) or via using collaterals (technique 2). The modified arteriotomy suture techniques are simple, safe, and applicable to almost all cases of CEA. CONCLUSION: Two modified arteriotomy suture techniques could reduce perioperative ischemic complications by reducing the cerebral ischemic time.
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Due to usability features, practical applications, and its lack of intrusiveness, face recognition technology, based on information, derived from individuals' facial features, has been attracting considerable attention recently. Reported recognition rates of commercialized face recognition systems cannot be admitted as official recognition rates, as they are based on assumptions that are beneficial to the specific system and face database. Therefore, performance evaluation methods and tools are necessary to objectively measure the accuracy and performance of any face recognition system. In this paper, we propose and formalize a performance evaluation model for the biometric recognition system, implementing an evaluation tool for face recognition systems based on the proposed model. Furthermore, we performed evaluations objectively by providing guidelines for the design and implementation of a performance evaluation system, formalizing the performance test process.
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Inteligencia Artificial , Biometría/métodos , Cara/anatomía & histología , Interpretación de Imagen Asistida por Computador/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Técnica de Sustracción , Humanos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The positions of unicompartmental femoral components do not always follow the neutral center of the medial distal femoral condyle. The biomechanical effect of the center of the distal femoral condyle has not yet been evaluated, and the optimal femoral position in unicompartmental knee arthroplasty (UKA) is yet to be biomechanically justified. The purpose of this study was to evaluate, using finite element analysis, the effect of the center of the distal femoral component on the biomechanical outcomes of UKA with respect to the contact stresses in the polyethylene (PE) insert and articular cartilage. METHODS: Five models in which the centers of the distal femoral components were translated by three millimeters and five millimeters to the medial and lateral sides, respectively, from the neutral position were modeled and analyzed in a gait loading condition. RESULTS: The contact stresses on the PE insert increased as the center of the femoral component translated to the lateral side and, in contrast, the contact stresses decreased as it translated to the medial side. For the articular cartilage the contact stresses increased and decreased as the center of the femoral component translated to the medial and lateral sides. CONCLUSION: This study implied that the best position for the femoral component in UKA could be the center of the distal femoral condyle. Femoral component position could be one of the sensitive factors that influenced the contact stresses on the PE insert and articular cartilage, and the postoperative significance of the femoral component position in UKA.
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Artroplastia de Reemplazo de Rodilla/métodos , Cartílago Articular/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Prótesis de la Rodilla , Osteoartritis de la Rodilla/cirugía , Fenómenos Biomecánicos , Cartílago Articular/fisiopatología , Cartílago Articular/cirugía , Femenino , Fémur/diagnóstico por imagen , Fémur/fisiopatología , Fémur/cirugía , Análisis de Elementos Finitos , Humanos , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Imagen por Resonancia Magnética , Masculino , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Polietileno , Rango del Movimiento Articular , Estrés Mecánico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Patients with atopic dermatitis (AD) often resort to the internet for disease-related information. We believe that dermatologists be informed about the current accessibility of information to patients and the potential for misleading patients into making poor treatment decisions. OBJECTIVE: The study was carried out in order to determine the nature of AD-related information available on the internet in Korea, and to identify any changes since our last survey in 2005. The quality of information offered and the involvement of medical doctors in certain websites were also investigated. METHODS: Taking into account the current search engine market share in Korea, we gathered all search results obtained from the three major search engines using the keyword 'atopy', and investigated the nature of the information retrieved. RESULTS: The search results showed less commercial sites than our previous study in 2005. There is a dramatic increase in the number of public bodies offering information about AD. In addition, the quality of information available online has improved since our last survey. CONCLUSION: The phenomenon of 'commercial overcrowding' seems to have stabilized. As AD becomes a more social phenomenon, patients are better informed than ever before. However, the information available on the internet still requires to be accompanied by consultation by dermatologists. We believe that self-regulation using a format such as the Health on the Net Foundation's code of conduct (HONcode) may improve the quality of online information accessible to patients with AD in Korea.
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BACKGROUND: Bone morphogenetic proteins (BMPs) are being evaluated as candidates for periodontal and bone regenerative therapy. However, the research on recombinant human bone morphogenetic protein-4 (rhBMP-4) has been insufficient to evaluate its capacity to enhance bone formation and its carrier system. The purpose of this study was to evaluate the bone regenerative effect of rhBMP-4 delivered with an absorbable collagen sponge (ACS) or beta-tricalcium phosphate (beta-TCP). We also compared the potential of beta-TCP to that of ACS as a carrier system for rhBMP-4. METHODS: Eight-mm calvarial critical-sized defects were created in 100 male Sprague-Dawley rats. The animals were divided into 5 groups of 20 animals each. The defects were treated with rhBMP-4/ACS (rhBMP-4 at 0.05 mg/ml), rhBMP-4/beta-TCP (rhBMP-4 at 0.05 mg/ml), ACS alone, beta-TCP alone, or left untreated for surgical control. The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated radiodensitometrically, histologically, and histomorphometrically. RESULTS: The results of radiodensitometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups were more radiopaque than other groups at both 2 and 8 weeks (P < 0.01). The histologic observations were as follows: in the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups, new bone was evident at the defect sites at 2 weeks and 8 weeks. The results of histomorphometric analysis were as follows: the rhBMP-4/ACS and the rhBMP-4/beta-TCP groups had more bone (%) than other groups at both 2 and 8 weeks (P < 0.01). CONCLUSIONS: Surgical implantation of rhBMP-4/ACS may be used to support bone regeneration in the rat calvarial critical-sized defect, and rhBMP-4/beta-TCP may be able to regenerate bone in the rat calvarial critical-sized defect without complication. In addition, both ACS and beta-TCP may be considered as available carriers for rhBMP-4.
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Enfermedades Óseas/tratamiento farmacológico , Proteínas Morfogenéticas Óseas/uso terapéutico , Regeneración Ósea/efectos de los fármacos , Cráneo/efectos de los fármacos , Absorciometría de Fotón , Animales , Materiales Biocompatibles , Densidad Ósea/efectos de los fármacos , Enfermedades Óseas/patología , Proteína Morfogenética Ósea 4 , Proteínas Morfogenéticas Óseas/administración & dosificación , Fosfatos de Calcio , Portadores de Fármacos , Esponja de Gelatina Absorbible , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes , Cráneo/patologíaRESUMEN
Spondyloepiphyseal dysplasia congenita (SEDC), an inherited chondrodysplasia, occurs through a mutation in the COL2A1 gene encoding the type II procollagen alpha1 chain, proalpha1 (II). Recently, the authors studied two Korean patients with SEDC. Both these patients had short stature, os odontoideum with or without atlantoaxial instability, platyspondyly, and epiphyseal dysplasia limited to the femoral heads. The more seriously affected patient had shorter height (125 cm), atlantoaxial instability associated with os odontoideum, flat feet, and cleft palate, absence of the femoral head on radiographic and magnetic resonance imaging (MRI), and dislocated proximal femur. The less seriously affected patient was taller (145 cm) and had no atlantoaxial instability, absence of the femoral head on radiography with visible cartilage anlage on MRI, and subluxated cartilaginous femoral head. A mutation analysis was performed using direct sequencing. Two novel dominant mutations were found in the COL2A1 gene of these two patients: G277V and G238S, respectively. Although glycine was substituted with valine and serine in the proalpha1 (II) of these two patients, their phenotypes were significantly different in physical and radiologic evaluations.
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Colágeno Tipo II/genética , Cabeza Femoral/anomalías , Mutación Missense , Osteocondrodisplasias/genética , Adolescente , Adulto , Articulación Atlantoaxoidea , Análisis Mutacional de ADN , Articulación de la Cadera/diagnóstico por imagen , Humanos , Inestabilidad de la Articulación/genética , Masculino , Osteocondrodisplasias/diagnóstico por imagen , Fenotipo , Análisis de Secuencia , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The aim of this study was to evaluate the efficiency of the intracytoplasmic morphologically selected sperm injection (IMSI) technique compared with conventional ICSI and previous ICSI attempts in oligo-astheno-teratozoospermia (OAT) patients. METHODS: The sperms were selected under high magnification (6,600×) and used to induce fertilization in previous ICSI patients by IMSI. These results were compared with previous conventional ICSI cycles in patients with OAT infertility. RESULTS: These results demonstrated no significant difference in the fertilization rate between IMSI and previous ICSI cycles (67.7% vs. 65.0%). However, the pregnancy and implantation rates with IMSI were significantly higher than those of the ICSI cycles (33.3% vs. 12.5% and 14.6% vs. 5.4%, respectively; p<0.05). The miscarriage rate among pregnant patients (18.2% vs. 37.5%) showed no statistically significant difference between groups. CONCLUSION: Compared to conventional ICSI, this study found that IMSI increased the IVF-ET success rates in patients with OAT.
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We characterized the cellular properties of cancer stem-like cells (CSLCs) isolated from immortalized MDA-MB453 human breast cancer cells in culture. We showed that although the expression of Octamer-binding transcription factor-4 (OCT4) correlates to stemness in these CSLCs, OCT4 knockdown does not induce their differentiation. Our results suggest that the differentiation program in MDA-MB453 CSLCs is blocked at a step upstream of the transcription of the OCT4 promoter, allowing CSLCs to maintain their population through asymmetric cell division during many repeated passages. Comparative expression analysis indicates that only a subset of genes and signaling pathways known to be associated with survival and maintenance of CSCs are selectively expressed in CSLCs, as compared with non-CSLCs fractionated from the same parental MDA-MB453 cells. These results suggest that selective expression of a limited number of genes may be sufficient for establishment and maintenance of CSLCs with high tumorigenicity.