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In this study, we investigated the effect of the stacking order of metal precursors on the formation of volume defects, such as blisters and nanopores, in CZTSSe thin-film solar cells. We fabricated CZTSSe thin films using three types of metal-precursor combinations, namely, Zn/Cu/Sn/Mo, Cu/Zn/Sn/Mo, and Sn/Cu/Zn/Mo, and studied the blister formation. The blister-formation mechanism was based on the delamination model, taking into consideration the compressive stress and adhesion properties. A compressive stress could be induced during the preferential formation of a ZnSSe shell. Under this stress, the adhesion between the ZnSSe film and the Mo substrate could be maintained by the surface tension of a metallic liquid phase with good wettability, or by the functioning of ZnSSe pillars as anchors, depending on the type of metal precursor used. Additionally, the nanopore formation near the back-contact side was found to be induced by the columnar microstructure of the metal precursor with the Cu/Zn/Mo stacking order and its dezincification. Based on the two volume-defect-formation mechanisms proposed herein, further development of volume-defect-formation suppression technology is expected to be made.
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BACKGROUND: The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy. METHODS: This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay. RESULTS: This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, p = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453-207.870, p = 0.024). CONCLUSION: Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group.
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OBJECTIVE: Esterified collagen (EC) can be functionalized with heparin to enhance islet graft stability. Growth factors secreted by human adipose-derived stem cells (hADSCs) can bind efficiently to EC-heparin (EC-Hep), which enhances revascularization and cell protection. We investigated the therapeutic potential of a combined heparin-esterified collagen-hADSC (HCA)-islet sheet to enhance islet engraftment. RESEARCH DESIGN AND METHODS: This study was designed to assess the efficiency of using EC-Hep as a scaffold for subcutaneous islet transplantation in diabetic athymic mice. After the hADSC-cocultured islets were seeded in the EC-Hep scaffold, islet function was measured by glucose-stimulated insulin secretion test and growth factors in the culture supernatants were detected by protein array. Islet transplantation was performed in mice, and graft function and survival were monitored by measuring the blood glucose levels. ß-Cell mass and vascular densities were assessed by immunohistochemistry. RESULTS: The EC-Hep composite allowed sustained release of growth factors. Secretion of growth factors and islet functionality in the HCA-islet sheet were significantly increased compared with the control groups of islets alone or combined with native collagen. In vivo, stable long-term glucose control by the graft was achieved after subcutaneous transplantation of HCA-islet sheet due to enhanced capillary network formation around the sheet. CONCLUSIONS: The findings indicate the potential of the HCA-islet sheet to enhance islet revascularization and engraftment in a hADSC dose-dependent manner, following clinical islet transplantation for the treatment of diabetes mellitus.
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Diabetes Mellitus Experimental , Células Secretoras de Insulina , Animales , Colágeno , Diabetes Mellitus Experimental/terapia , Heparina , Ratones , Células MadreRESUMEN
BACKGROUND: Flowable hemostatic agents may be more advantageous than nonflowable hemostats, as they have capability to cover irregular wound surfaces, fill deep lesions, and easily remove excess materials with irrigation. In this study, we evaluated the hemostatic efficacy of the collagen hemostatic matrix (CHM) compared to FloSeal® via incisions in the heart and cardiac vessels in a porcine model. METHODS: In each of the two female pigs, a total of two incisions were made in seven locations: right atrium (RA), right ventricle (RV), and cardiac vessels, such as the innominate vein (IV), superior vena cava (SVC), pulmonary artery (PA), coronary artery (CA), and aorta. Hemostatic agents were applied directly to the bleeding wounds. In certain location, one incision was treated with the CHM and the other with FloSeal®, and the time to hemostasis and the degree of bleeding of the two agents were assessed and compared. One week after surgery, the animals were sacrificed, and specimens were collected for histologic evaluation. RESULTS: Bleeding from the vessels with relatively low pressure (the IV, SVC, and RA) was controlled within 1-2 minutes using both a CHM and FloSeal®. Bleeding from the vessels with high blood pressure (the RV, PA, CA, and aorta) was controlled within 3-10 minutes with the CHM. However, hemostasis in the PA and CA was not achieved with FloSeal®. Histological analysis revealed that the use of both the CHM and FloSeal® resulted in foreign body reactions of similar severity. CONCLUSIONS: The hemostatic effect and safety of the CHM may be similar to that of FloSeal®. Further clinical studies must be conducted to validate our results.
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Telomere length (TL) is a prognostic indicator in Caucasian chronic lymphocytic leukemia (CLL), but its significance in Asian CLL remains unknown. To investigate the prognostic significance of TL and its correlation with cytogenetic aberrations and somatic mutations, we analyzed TL measurements at the cellular level by interphase fluorescence in situ hybridization in patients with CLL in Korea. The present study enrolled 110 patients (41 females and 69 males) diagnosed with CLL according to the World Health Organization criteria (2001-2017). TLs of bone marrow nucleated cells at the single-cell level were measured by quantitative fluorescence in situ hybridization (Q-FISH) in 71 patients. The correlations of TL with clinical characteristics, cytogenetic aberrations, genetic mutations, and overall survival were assessed. The median value of mean TL in CLL patients (T/C ratio 7.46 (range 1.19-18.14) was significantly shorter than that in the normal controls (T/C ratio 15.28 (range 8.59-24.93) (p < 0.001). Shorter TLs were associated with complex karyotypes (p = 0.030), del(11q22) (p = 0.023), presence of deletion and/or mutation in ATM and/or TP53 (p = 0.019), and SH2B3 mutation (p = 0.015). A shorter TL was correlated with lower hemoglobin levels and adverse survival (mean TL < 9.35, p = 0.021). When the proportion of cells with extremely short TLs (< 7.61) was greater than 90%, CLL patients showed poor survival (p = 0.002). Complex karyotypes, TP53 mutation, and the number of mutated genes were determined to be significant adverse variables by multivariable Cox analysis (p = 0.011, p = 0.002, and p = 0.002, respectively). TL was attrited in CLL, and attrited telomeres were correlated with adverse survival and other well-known adverse prognostic factors. We infer that TL is an independent adverse prognostic predictor in Korean CLL.
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Leucemia Linfocítica Crónica de Células B/genética , Mutación , Homeostasis del Telómero , Proteínas Adaptadoras Transductoras de Señales/genética , Anciano , Proteínas de la Ataxia Telangiectasia Mutada/genética , Biomarcadores de Tumor/genética , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , República de Corea , Proteína p53 Supresora de Tumor/genéticaRESUMEN
For kesterite copper zinc tin sulfide/selenide (CZTSSe) solar cells to enter the market, in addition to efficiency improvements, the technological capability to produce flexible and large-area modules with homogeneous properties is necessary. Here, we report a greater than 10% efficiency for a cell area of approximately 0.5 cm2 and a greater than 8% efficiency for a cell area larger than 2 cm2 of certified flexible CZTSSe solar cells. By designing a thin and multi-layered precursor structure, the formation of defects and defect clusters, particularly tin-related donor defects, is controlled, and the open circuit voltage value is enhanced. Using statistical analysis, we verify that the cell-to-cell and within-cell uniformity characteristics are improved. This study reports the highest efficiency so far for flexible CZTSSe solar cells with small and large areas. These results also present methods for improving the efficiency and enlarging the cell area.
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Metales/química , Energía Solar , Espectrometría por Rayos XRESUMEN
BACKGROUND: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. METHODS: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. RESULTS: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. CONCLUSIONS: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.
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Fragilidad Osmótica/fisiología , Esferocitos/metabolismo , Esferocitosis Hereditaria/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteína 1 de Intercambio de Anión de Eritrocito/genética , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Ancirinas/genética , Ancirinas/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Niño , Preescolar , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Femenino , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Lactante , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Mutación/genética , Fragilidad Osmótica/genética , Patología Molecular , República de Corea , Espectrina/genética , Espectrina/metabolismo , Esferocitosis Hereditaria/genética , Adulto JovenRESUMEN
Idiopathic hypereosinophilia (IHE)/idiopathic hypereosinophilic syndrome (IHES) has been defined by a persistent elevation of the blood eosinophil count exceeding 1.5×103/µL, without evidence of reactive or clonal causes. While T-cell clonality assessment has been recommended for unexplained hypereosinophilia, this approach is not often applied to routine practice in the clinic. We hypothesized that the clonality would exist in a subset of IHE/IHES patients. We aimed to investigate the candidate mutations and T-cell clonality in IHE/IHES and to explore the role of mutations in eosinophil proliferation. We performed targeted capture sequencing for 88 genes using next-generation sequencing, T-cell receptor (TCR) gene rearrangement assays, and pathway network analysis in relation to eosinophil proliferation. By targeted sequencing, 140 variants in 59 genes were identified. Sixteen out of 30 patients (53.3%) harbored at least one candidate mutation. The most frequently affected genes were NOTCH1 (26.7%), SCRIB and STAG2 (16.7%), and SH2B3 (13.3%). Network analysis revealed that our 21 candidate genes (BIRC3, BRD4, CSF3R, DNMT3A, EGR2, EZH2, FAT4, FLT3, GATA2, IKZF, JAK2, MAPK1, MPL, NF1, NOTCH1, PTEN, RB1, RUNX1, TET2, TP53 and WT1) are functionally linked to the eosinophilopoietic pathway. Among the 21 candidate genes, five genes (MAPK1, RUNX1, GATA2, NOTCH1 and TP53) with the highest number of linkages were considered major genes. A TCR assay revealed that four patients (13.3%) had a clonal TCR rearrangement. NOTCH1 was the most frequently mutated gene and was shown to be a common node for eosinophilopoiesis in our network analysis, while the possibility of hidden T cell malignancy was indwelling in the presence of NOTCH1 mutation, though not revealed by aberrant T cell study. Collectively, these results provide new evidence that mutations affecting eosinophilopoiesis underlie a subset of IHE/IHES, and the candidate genes are inferred to act their potential roles in the eosinophilopoietic pathway.
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Células Clonales , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Síndrome Hipereosinofílico/genética , Adulto , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mutación , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
Mutational profiles of 153 Korean myelodysplastic syndrome (MDS) patients were investigated. Sequencing of 87 genes presented similar mutational profiles in Korean MDS patients compared with previous reports. The most frequently mutated genes were ASXL1 (22.9%), U2AF1 (16.3%), TP53 (13.7%), RUNX1 (10.5%), TET2 (10.5%), DNMT3A (8.5%), and SRSF2 (8.5%). The U2AF1 mutation frequency was higher, with different frequencies in the mutated sites of U2AF1 (S34Y, 6/25; S34F, 11/25; and Q157P 8/25). The U2AF1 S34Y mutation was strongly associated with isolated trisomy 8 (5/6, 83%) and was characterized by a younger age of MDS onset (median, 39 years). The S34F mutation was associated with trisomy 8 (6/11, 55%) and del(20q) (3/11, 27%). Data from 10 literatures (total 3460 patients) of 229 U2AF1-mutated cases revealed a significant association between the S34Y and trisomy 8 in Asians (P=0.0001), but not in Caucasians (P=0.080). We infer that U2AF1 S34 mutations characterize a distinct subgroup of MDS: younger age of onset and differential associations with particular cytogenetic aberrations depending on specific mutations [S34Y to +8; S34F to +8 and del(20q)]. The impact and causal relationship between U2AF1 S34 and trisomy 8 need to be elucidated, which might contribute to design of tailored treatments.
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Síndromes Mielodisplásicos/genética , Factor de Empalme U2AF/genética , Trisomía/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Cromosomas Humanos Par 8/genética , Análisis Mutacional de ADN , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Población Blanca/genética , Adulto JovenAsunto(s)
Síndromes de Inmunodeficiencia/diagnóstico , Receptores CXCR4/genética , Verrugas/diagnóstico , Agammaglobulinemia/etiología , Médula Ósea/patología , Eliminación de Gen , Humanos , Síndromes de Inmunodeficiencia/genética , Lactante , Masculino , Neutropenia/etiología , Enfermedades de Inmunodeficiencia Primaria , Verrugas/genéticaRESUMEN
Choice of appropriate biomaterial is a key factor for the success of recombinant human bone morphogenetic protein (rhBMP)-2 therapy. Inspired by osteogenic cell-differentiating and osteoclast-suppressing capabilities of alendronate (ALN), we manufactured a composite type of ALN-loaded collagen sponge (ALN-CS), which controls the early detrimental effect of high-dose rhBMP-2. This study aimed to evaluate ALN-CS as a high-dose rhBMP-2 carrier by investigating its initial biomolecular effect and efficacy on intramembranous ossification at 1, 4, 8, and 24 weeks using a rat calvarial defect model compared with nonloaded CS. The in vitro rhBMP-2 release in the ALN-CS showed a low initial burst and steady release phase during the rest period despite lack of calcium compared with that in CS alone. ALN release showed the same tendency as rhBMP-2 release. In vitro characterization showed that osteoblast differentiation and mineralization of mesenchymal stromal cells were more enhanced with ALN-CS. The ALN-CS-BMP group showed higher expression of bone-forming and -resorbing markers in vivo than the CS-BMP group after the first 7 days, which might be attributable to the relatively large amount of rhBMP-2 remaining. However, osteoclast activation in the ALN-CS-BMP group was significantly reduced compared with the CS-BMP group. Radiological and histological analyses revealed that ALN-CS-BMP promoted early and dense ossification at the initial defect, with 100% greater bone mass, 20% greater bone density, and less fatty marrow tissue than CS-BMP, which continued during the whole healing period. However, CS or ALN-CS alone failed to show complete defect closure even at the 24-week healing interval. Our results demonstrate that ALN-CS has remarkable advantages over CS alone in high-dose BMP-2 delivery, with potent suppression of resorption, early and dense ossification at the target area with less fatty marrow formation, and continuation of bone quality over the long term, which highlights its great clinical potential as a rhBMP carrier for bone regeneration at intramembranous ossification sites.
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Alendronato , Proteína Morfogenética Ósea 2 , Calcificación Fisiológica/efectos de los fármacos , Colágeno , Osteoblastos , Osteogénesis/efectos de los fármacos , Cráneo , Alendronato/química , Alendronato/farmacología , Animales , Antígenos de Diferenciación/biosíntesis , Proteína Morfogenética Ósea 2/química , Proteína Morfogenética Ósea 2/farmacología , Diferenciación Celular/efectos de los fármacos , Colágeno/química , Colágeno/farmacología , Humanos , Masculino , Osteoblastos/metabolismo , Osteoblastos/patología , Ratas , Ratas Sprague-Dawley , Cráneo/lesiones , Cráneo/metabolismo , Cráneo/patologíaRESUMEN
BACKGROUND: Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA. METHODS: The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated. RESULTS: MDS patients had shorter interphase TL than normal healthy donors (P<0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P=0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P=0.003, 0.001, 0.005, 0.005, and 0.013, respectively). CONCLUSIONS: The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS.
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Síndromes Mielodisplásicos/patología , Telomerasa/metabolismo , Telómero/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Células de la Médula Ósea/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Interfase , Estimación de Kaplan-Meier , Cariotipificación , Masculino , Metafase , Persona de Mediana Edad , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Acortamiento del TelómeroRESUMEN
Chronic lymphocytic leukemia (CLL) is extremely rare in Asian countries and there has been one report on genetic changes for 5 genes (TP53, SF3B1, NOTCH1, MYD88, and BIRC3) by Sanger sequencing in Chinese CLL. Yet studies of CLL in Asian countries using Next generation sequencing have not been reported. We aimed to characterize the genomic profiles of Korean CLL and to find out ethnic differences in somatic mutations with prognostic implications. We performed targeted sequencing for 87 gene panel using next-generation sequencing along with G-banding and fluorescent in situ hybridization (FISH) for chromosome 12, 13q14.3 deletion, 17p13 deletion, and 11q22 deletion. Overall, 36 out of 48 patients (75%) harbored at least one mutation and mean number of mutation per patient was 1.6 (range 0-6). Aberrant karyotypes were observed in 30.4% by G-banding and 66.7% by FISH. Most recurrent mutation (>10% frequency) was ATM (20.8%) followed by TP53 (14.6%), SF3B1 (10.4%), KLHL6 (8.3%), and BCOR (6.25%). Mutations of MYD88 was associated with moderate adverse prognosis by multiple comparisons (P = 0.055). Mutation frequencies of MYD88, SAMHD1, EGR2, DDX3X, ZMYM3, and MED12 showed similar incidence with Caucasians, while mutation frequencies of ATM, TP53, KLHL6, BCOR and CDKN2A tend to be higher in Koreans than in Caucasians. Especially, ATM mutation showed 1.5 fold higher incidence than Caucasians, while mutation frequencies of SF3B1, NOTCH1, CHD2 and POT1 tend to be lower in Koreans than in Caucasians. However, mutation frequencies between Caucasians and Koreans were not significantly different statistically, probably due to low number of patients. Collectively, mutational profile and adverse prognostic genes in Korean CLL were different from those of Caucasians, suggesting an ethnic difference, while profile of cytogenetic aberrations was similar to those of Caucasians.
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Sitios Genéticos , Genoma Humano , Leucemia Linfoide/genética , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Estudios de Casos y Controles , Aberraciones Cromosómicas , Femenino , Humanos , Leucemia Linfoide/etnología , Leucemia Linfoide/patología , Masculino , Persona de Mediana Edad , Tasa de Mutación , República de Corea , Población BlancaRESUMEN
BACKGROUND: Collagen exhibits ideal multifactorial action for preventing tissue adhesions. This study examined the efficacy of ionized collagen in preventing tissue adhesion after surgical procedures. MATERIALS AND METHOD: Ionized collagen was prepared using the esterification technique of natural collagen. Three forms of collagen materials (membrane, film, and gel) were compared with three commercialized materials (oxidized regenerated cellulose membrane [OC membrane], hyaluronic acid and carboxymethylcellulose film, and gel [HC film and HC gel]) in a rat cecum abrasion model. Antiadhesive activity and histologic findings were assessed. RESULT: The incidence of adhesion was reduced significantly in all test groups compared to the sham-operated control group (100% in control, 14.3% in collagen membrane, 63.6% in collagen film, 25.0% in collagen gel, 55.6% in OC membrane, 75% in HC film, and 83.3% in HC gel). All collagen materials of the three forms exhibited a significant reduction in adhesion grade compared with the sham operation, whereas no significant difference was found among these three different forms. The collagen membrane showed significantly less adhesion grade, less inflammation and more regenerative features compared to widely used conventional materials. CONCLUSIONS: This preclinical investigation indicated that ionized collagen materials readily formed clinically suitable shapes for easy handling without the need for any complex processing and effectively reduced postoperative tissue adhesion profiles compared to conventional antiadhesive agents.
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Materiales Biocompatibles/uso terapéutico , Ciego/cirugía , Colágeno/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Adherencias Tisulares/prevención & control , Animales , Carboximetilcelulosa de Sodio/uso terapéutico , Celulosa Oxidada/uso terapéutico , Ácido Hialurónico/uso terapéutico , Incidencia , Masculino , Complicaciones Posoperatorias/epidemiología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Adherencias Tisulares/epidemiología , Adherencias Tisulares/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS. METHODS: We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed. RESULTS: MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (≥80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively). CONCLUSIONS: The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH.
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Mutación , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Telómero/patología , Adolescente , Adulto , Anciano , Células de la Médula Ósea , Aberraciones Cromosómicas , Femenino , Inestabilidad Genómica , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Acortamiento del Telómero , Adulto JovenRESUMEN
Sustained release of bone morphogenetic protein (BMP)-2 by heparin-contained biomaterials is advantageous for bone tissue regeneration using low-dose BMP-2. However, its effect with high-dose BMP-2 is still unclear and should be clarified considering the clinical use of a high dose of BMP-2 in spine and oral surgery. This study aimed to evaluate the efficacy of a heparin-conjugated collagen sponge (HCS) with high-dose BMP-2 delivery by investigating in vivo initial osteogenic regulation and bone healing over 12 weeks in comparison with that of an absorbable collagen sponge (ACS). The in vitro BMP-2 release profile in the HCS exhibited a lower burst followed by a sustained release of BMP-2, whereas that of the ACS showed an initial burst phase only. As a result of a lower burst, the HCS-BMP group showed higher expression of bone-forming/resorbing markers and enhanced activation of osteoclasts than the ACS-BMP group within the scaffold of defect after 7 days, which is presumed to be because of retention of relatively higher amounts of BMP-2. However, the surrounding calvariae were less resorbed in the HCS-BMP group, compared with the aggressive resorptive response in the ACS-BMP group. Microcomputed tomography and histology revealed that HCS-BMP guided more effective bone regeneration of central defect over time inducing minor ossification at the defect exterior, whereas ACS-BMP exhibited excessive ossification at the defect exterior. These results showed that HCS-mediated BMP-2 delivery at a high dose has advantages over ACS, including less early resorption of surrounding bone tissue and higher efficacy in compact bone regeneration over a longer period, highlighting a clinical feasibility of this technology.
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Proteína Morfogenética Ósea 2 , Resorción Ósea/tratamiento farmacológico , Colágeno , Heparina , Osteoclastos/metabolismo , Animales , Proteína Morfogenética Ósea 2/química , Proteína Morfogenética Ósea 2/farmacocinética , Proteína Morfogenética Ósea 2/farmacología , Resorción Ósea/metabolismo , Resorción Ósea/patología , Colágeno/química , Colágeno/farmacocinética , Colágeno/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Heparina/química , Heparina/farmacocinética , Heparina/farmacología , Osteoclastos/patología , Ratas , Ratas Sprague-DawleyRESUMEN
We performed cytoplasmic fluorescence in situ hybridization assays of light chain amyloidosis (AL). In total, 234 patients were enrolled: 28 patients with AL, 24 with monoclonal gammopathy of undetermined significance (MGUS), and 182 with multiple myeloma (MM). Chromosomal abnormalities were detected in 13 of 22 (59%) AL patients without MM. All 13 patients demonstrated IGH rearrangement, and t(11;14)/IGH-CCND1 was most frequent (32%). Chromosome gain was not observed in AL patients without MM. These findings were dissimilar to findings in MGUS patients, in whom trisomy 9 was the most frequent abnormality. Of 6 AL patients with MM, 5 (83%) patients had cytogenetic abnormalities: 1q gain (4/6, 67%), gains of chromosome 9 (3/6, 50%), IGH rearrangement and RB1 (13q) deletions (2/6 each, 33%). The percentage of clonal plasma cells among total plasma cells was variable (median, 75%; range, 16-100%) for AL patients without MM, which was lower than the results for MM patients (median 100%). The overall survival of AL patients without MM was not significantly different according to the presence of cytogenetic abnormalities (P=0.510). In summary, among Korean AL patients, IGH rearrangement was the most frequent cytogenetic abnormality and cytogenetic aberration patterns differ compared with MGUS and MM patients.
Asunto(s)
Amiloidosis/patología , Aberraciones Cromosómicas , Cadenas Ligeras de Inmunoglobulina/genética , Gammopatía Monoclonal de Relevancia Indeterminada/patología , Mieloma Múltiple/patología , Células Plasmáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/genética , Amiloidosis/mortalidad , Cromosomas Humanos Par 13/genética , Femenino , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Pronóstico , Tasa de SupervivenciaRESUMEN
We have investigated the effects of adding (Ta) ions to InSnO thin films by co-sputtering on the performance of InSnO thin film transistors (TFTs). TaInSnO TFTs exhibited significantly lower off currents and higher on/off current ratios. Ta ions, owing to their strong affinity to oxygen suppress the formation of free electron carriers in thin films; and hence, play an important role in enhancing the electrical characteristics of the TFTs. The optimized TaInSnO TFTs showed high on/off ratios and low subthreshold swings.
RESUMEN
Cu2ZnSnS4 (CZTS) solar cells are attracting significant attention as an alternative to CIGS (Culn1-xGa(x)S2) solar cells because of the non-toxic and inexpensive constituent elements of CZTS. Recently, solution-based deposition methods are being developed because they have advantages such as suitability for use in large-area deposition, high-throughput manufacturing, and a very short energy payback time with drastically lower manufacturing costs. In this work, we fabricated solution-based CZTS thin films and investigated them in order to observe the effects of sulfurization temperature on CZTS thin films. We confirmed the grain size, morphology, chemical composition, crystallinity, and electrical properties of CZTS thin films depending on various sulfurization temperatures.
RESUMEN
Nanoporous p-type semiconductor thin films prepared by a simple solution-based process with appropriate thermal treatment and three-dimensional (3D) p-n junction solar cells fabricated by depositing n-type semiconductor layers onto the nanoporous p-type thin films show considerable photovoltaic performance compared with conventional thin film p-n junction solar cells. Spin-coated p-type Cu2ZnSnS4 (CZTS) thin films prepared using metal chlorides and thiourea show unique nanoporous thin film morphology, which is composed of a cluster of CZTS nanograins of 50-500 nm, and the obvious 3D p-n junction structure is fabricated by the deposition of n-type CdS on the nanoporous CZTS thin films by chemical bath deposition. The photovoltaic properties of 3D p-n junction CZTS solar cells are predominantly affected by the scale of CZTS nanograins, which is easily controlled by the sulfurization temperature of CZTS precursor films. The scale of CZTS nanograins determines the minority carrier transportation within the 3D p-n junction between CZTS and CdS, which are closely related with the photocurrent of series resistance of 3D p-n junction solar cells. 3D p-n junction CZTS solar cells with nanograins below 100 nm show power conversion efficiency of 5.02%, which is comparable with conventional CZTS thin film solar cells.