Introduction
Persistent lymphatic leakage from the surgical drain is a troubling complication occasionally encountered postoperatively. This study investigated lymphatic leaks after renal or liver ...transplantation, comparing the treatment efficacy of traditional catheter drainage vs. minimally invasive lymphatic interventions. We also discuss access and treatment targets considering the physiology of lymphatic flow.
Methods
Between September 2018 and September 2020, 13 patients with lymphatic leakage were treated with minimally invasive lymphatic interventions; 11 had received a renal transplant, and two received a liver transplant. The control group included 10 patients with postrenal transplant lymphatic leakage treated with catheter drainage. The treatment efficacy of catheter drainage, lymphatic interventions, and different targets of embolization were compared.
Results
The technical success rate for lymphatic intervention was 100%, and the clinical success rate was 92%, with an 82.9% reduction in drain volume on the first day after treatment. The duration to reach clinical success was 5.9 days with lymphatic intervention, and 33.9 days with conservative catheter drainage.
Conclusion
Lymphangiography and embolization are minimally invasive and efficient procedures for treating persistent lymphatic leaks after renal or liver transplantation. We suggest prompt diagnosis and embolization at upstream lymphatics to reduce the duration of drain retention, days of hospitalization, and associated comorbidities.
Mercaptopurine-induced neutropenia can interrupt chemotherapy and expose patients to infection during childhood acute lymphoblastic leukemia (ALL) treatment. Previously, six candidate gene variants ...associated with mercaptopurine intolerance were reported. Herein, we investigated the association between the mean tolerable dose of mercaptopurine and these genetic variants in Taiwanese patients.
In total, 294 children with ALL were treated at the National Taiwan University Hospital from April 1997 to December 2017. Germline variants were analyzed for NUDT15, SUCLA2, TPMT, ITPA, PACSIN2, and MRP4. Mean daily tolerable doses of mercaptopurine in the continuation phase of treatment were correlated with these genetic variants.
Mercaptopurine intolerance was significantly associated with polymorphisms in NUDT15 (P value < 0.0001). Patients with SUCLA2 variants received lower mercaptopurine doses (P value = 0.0119). The mean mercaptopurine doses did not differ among patients with TPMT, ITPA, MRP4, and PACSIN2 polymorphisms (P value = 0.9461, 0.5818, and 0.7951, respectively). After multivariable linear regression analysis, only NUDT15 variants retained their clinically significant correlation with mercaptopurine intolerance (P value < 0.0001).
In this cohort, the major genetic determinant of mercaptopurine intolerance was NUDT15 in Taiwanese patients.
NUDT15 causes mercaptopurine intolerance in children with ALL. The NUDT15 variant is a stronger predictor of mercaptopurine intolerance than TPMT in a Taiwanese cohort. This finding is similar with studies performed on Asian populations rather than Caucasians. Pre-emptive genotyping of the patients' NUDT15 before administering mercaptopurine may be more helpful than genotyping TPMT in Asians.
Diindeno‐fused dibenzoa,hanthracene 6 and diindeno‐fused dibenzoc,lchrysene 9 contain the key moieties 1,4‐quinodipropene (1,4‐QDP) and 2,6‐naphthoquinodipropene (2,6‐NQDP), respectively, and they ...both have an open‐shell singlet ground state. The latter compound exhibits a strong biradical character and interesting properties, including a low ΔET−S (2.44 kcal mol−1), a small HOMO–LUMO gap (1.06 eV), a wide photoabsorption range (250–1172 nm), and a large two‐photon absorption cross‐section (σ=1342±56 GM). This work verifies that 6 has a slightly larger HOMO–LUMO gap and ΔET−S than its helical isomer diindeno2,1‐f:1′,2′‐jpicene (DIP), but is a much stronger two‐photon absorber, verifying the important effect of geometry on the photophysical properties.
Radical chemistry! Diindeno‐fused dibenzoa,hanthracene and dibenzoc,lchrysene, which contain the key moieties of 1,4‐quinodipropene (1,4‐QDP) and 2,6‐naphthoquinodipropene (2,6‐NQDP), respectively, both have singlet biradical character and many interesting properties. Compound 6 with the quasi‐planar structure is suitable for verifying the through‐space interactions of the singlet biradical helicene DIP (see scheme).
Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is ...hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λint play key roles. Up to the current stage, the majority of the reported organic NIR(II) emitters belong to those polymethines terminated by two symmetric chromophores. Such a design has proved to have a small λint that greatly suppresses the internal conversion. However, the imposition of symmetric chromophores is stringent, limiting further development of organic NIR(II) dyes in diversity and versatility. Here, we propose a new concept where as far as the emissive state of the any asymmetric polymethines contains more or less equally transition density between two terminated chromophores, λint can be as small as that of the symmetric polymethines. To prove the concept, we synthesize a series of new polymethines terminated by xanthen-9-yl-benzoic acid and 2,4-diphenylthiopyrylium derivatives, yielding AJBF1112 and AEBF1119 that reveal emission peak wavelength at 1112 and 1119 nm, respectively. The quantum yield is higher than all synthesized symmetric polymethines of 2,4-diphenylthiopyrylium derivatives (SC1162, 1182, 1185, and 1230) in this study. λint were calculated to be as small as 6.2 and 7.3 kcal/mol for AJBF1112 and AEBF1119, respectively, proving the concept. AEBF1119 was further prepared as a polymer dot to demonstrate its in vitro specific cellular imaging and in vivo tumor/bone targeting in the NIR(II) region.
The purpose of this study was to investigate the effects of simulation design, visual-motor integration, and spatial ability on students’ conceptual understandings of projectile motion and collision. ...We developed three simulations including two mobile applications (app) and a computer simulation. One app (TA) employed the multi-touch feature for virtual manipulation, the other (TAG) implemented the multi-touch and tilt features, while the computer simulation (CS) was performed using a mouse. 211 10th graders were assigned to the three simulation groups. The results indicated that on the items of basic concepts, the CS and TA groups performed significantly better than the TAG group, whereas for the advanced concepts, the TA and TAG groups scored significantly higher than the CS group. Also, high visual-motor integration students did significantly better on the advanced concepts than low visual-motor integration students. Additionally, the interaction effect between simulation design and spatial ability showed that the two apps had a similar effect on students with different levels of spatial ability. The results suggest that mobile apps could narrow the performance gap between students with different levels of spatial ability, but effective interactions with the multi-touch interface of apps may require new skills such as visual-motor integration.
•We examined the effects of simulation design and visual-motor integration (VMI).•The groups using mobile apps scored significantly higher on advanced concepts.•High VMI students did significantly better on the advanced concepts.•Mobile apps could narrow the gap between students with different spatial ability.
TP53 alterations are frequent relapse‐acquired mutations in childhood acute lymphoblastic leukemia (ALL). The present study evaluated the clinical significance of relapsed childhood ALL in Taiwan. ...Diagnostic and/or relapsed bone marrow or peripheral blood was obtained from 111 children with relapsed ALL who were initially treated by using Taiwan Pediatric Oncology Group (TPOG) ALL protocols from January 1997 to May 2018. Mutations were detected by PCR and sequencing, as well as by multiplex ligation‐dependent probe amplification to detect copy number alterations. Copy number and/or sequence alterations of TP53 were detected in 29% (28 of 98) and in 46% (6 of 13) of patients with relapsed B‐cell and T‐cell ALL, respectively. This incidence was much higher than that in several similar studies conducted in Caucasian populations. Seventy percent of all TP53 alterations were gained at relapse in 67 matched samples by back‐tracking matched diagnostic samples. TP53 alterations were associated with lower 5‐year event‐free survival (EFS) and overall survival (OS) rates (P = .013 and P = .0002, respectively). Multivariate analysis confirmed the prognostic significance of TP53 alterations. Forty‐five patients received hematopoietic stem‐cell transplantations post‐relapse. Patients with TP53 alterations (14/45) had inferior 5‐year EFS and OS than patients without TP53 alterations after transplantation (P = .002 and P = .001, respectively). The significance of these TP53 alterations for patients who received transplantations was confirmed by multivariate analysis. In conclusion, TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.
Relapsed pediatric ALL patients with TP53 alterations had inferior 5‐year EFS and OS. TP53 alterations were enriched and useful as prognostic markers in relapsed childhood ALL.
Evidence evaluating the risk of pneumonia in patients with obstructive sleep apnea is limited and mostly focuses on patients who receive continuous positive airway pressure (CPAP) therapy or on ...pediatric patients. We aimed to explore the risk of incident pneumonia among adults with sleep apnea, either with or without the need of CPAP therapy.
From Jan. 1, 2000, we identified adult patients with sleep apnea from the Taiwan National Health Insurance Research Database. A control cohort without sleep apnea, matched for age, sex and comorbidities, was selected for comparison. The 2 cohorts were followed until Dec. 31, 2010, and observed for occurrence of pneumonia.
Of the 34,100 patients (6816 study patients and 27,284 matched controls), 2757 (8.09%) had pneumonia during a mean follow-up period of 4.50 years, including 638 (9.36%) study patients and 2119 (7.77%) controls. Kaplan-Meier analysis showed a higher incidence of pneumonia among patients with sleep apnea (log rank test, p < 0.001). After multivariate adjustment, patients with sleep apnea experienced a 1.20-fold (95% confidence interval 1.10-1.31) increase in incident pneumonia. The risk was even higher among patients who received CPAP therapy.
Sleep apnea appeared to confer a higher risk for future pneumonia, possibly in a severity-dependent manner.
Abstract Purpose Deferasirox (DEFR), when administered BID, improves iron overload and decreases DEFR-related adverse effects in patients with β-thalassemia major. However, the pharmacokinetic (PK) ...disposition of DEFR and the iron–DEFR complex (Fe-DEFR2 ) in this dosing strategy is unclear. Methods Chromatographic analysis was performed using a solvent delivery system coupled to an HPLC-UV detector to determine the steady-state concentrations of DEFR (CDEFR ) and Fe-(DEFR)2 (CFe-DEFR2 ) in β-thalassemia major patients (n = 8) following either once-daily or BID dosing, during which the PK parameters of the 2 dosing schedules were compared. Findings An HPLC-UV system for the analysis of blood samples following solid-phase extraction was validated. Patients who received 40 mg/kg of DEFR had higher mean CDEFR and CFe-DEFR2 values at all sampling times. However, concentrations of iron-DEFR complex were similar in patients who received 30 or 40 mg/kg of DEFR in the once-daily group at the 6- to 24-hour sampling times. There was no significant difference in any of the PK parameters; however, DEFR administration BID increased the mean trough levels of DEFR (183.8 157.5 μmol/L) compared with once daily (87.7 56.8 μmol/L), whereas all the patients had increased peak levels per individual DEFR dose when they were switched from once daily to BID (139.0 59.8 μmol/L vs 289.2 145.8 μmol/L, respectively). Implications Splitting the dose increased the peak levels of DEFR per unit dose in all patients and tends to increase drug exposures, but there were no significant differences in DEFR PK parameter estimates. Switching from once daily to BID may be considered for patients with an inadequate response to chelation therapy to achieve optimal drug levels. Further research is needed with a larger sample size to determine the clinical importance of the significant results due to the interindividual variability of DEFR.
Reporter gene assays are essential for high-throughput analysis, such as drug screening or determining downstream signaling activation/inhibition. However, use of this technology has been hampered by ...the high cost of the substrate (e.g., d-Luciferin (d-Luc)) in the most common firefly luciferase (FLuc) reporter gene assay. Although alternate luciferase is available worldwide, its substrate has remained expensive, and a more affordable option is still in demand. Here, we present a membrane-tethered horseradish peroxidase (mHRP), a new reporter system composed of a cell membrane expressing HRP that can preserve its enzymatic function on the cell surface, facilitates contact with HRP substrates (e.g., ABTS and TMB), and avoids the cell lysis process and the use of the high-priced luciferase substrate. An evaluation of the light signal sensitivity of mHRP compared to FLuc showed that both had comparable signal sensitivity. We also identified an extended substrate half-life of more than 5-fold that of d-Luc. Of note, this strategy provided a more stable detection signal, and the cell lysis process is not mandatory. Furthermore, with this strategy, we decreased the total amount of time taken for analysis and increased the time of detection limit of the reporter assay. Pricing analysis showed a one-third to one twenty-eighth price drop per single test of reporter assay. Given the convenience and stability of the mHRP reporter system, we believe that our strategy is suitable for use as an alternative to the luciferase reporter assay.
Cyclopentadithiophene and methyl-2,5-dibromobenzoate have been copolymerised via palladium complex catalysed direct arylation. The methyl ester group in the benzoate unit is converted to the carboxyl ...group via saponification. The polymers are mixed with Si nanoparticles for use as conducting binders in the fabrication of an anode electrode in lithium ion batteries. The battery with the electrode incorporating the saponified polymer shows much higher specific capacity of up to 1820 mA h g
(total weight) and a higher stability compared with the battery including the polymer before the saponification.