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.
The evidence on whether Chinese herbal medicines affect outcome in patients with chronic kidney disease (CKD) is limited. Here we retrospectively explored the association of prescribed Chinese herbal ...medicine use and the risk of end-stage renal disease (ESRD) in patients with CKD. Patients with newly diagnosed CKD in the Taiwan National Health Insurance Research Database from 2000 to 2005 were categorized into new use or nonuse of prescribed Chinese herbal medicine groups. These patients were followed until death, dialysis initiation, or till the end of 2008. Among the 24,971 study patients, 11,351 were new users of prescribed Chinese herbal medicine after CKD diagnosis. Overall, after adjustment for confounding variables, the use group exhibited a significant 60% reduced ESRD risk (cause-specific hazard ratio 0.41, 95% confidence interval 0.37–0.46) compared with the nonuse group. The change was significantly large among patients using wind dampness–dispelling formulas (0.63, 0.51–0.77) or harmonizing formulas (0.59, 0.46–0.74), suggesting an independent association between specific Chinese herbal medicines and reduced ESRD risk. The findings were confirmed using propensity score matching, stratified analyses, and three weighting methods. However, dampness-dispelling and purgative formulas were associated with increased ESRD risk. Thus, specific Chinese herbal medicines are associated with reduced or enhanced ESRD risk in patients with CKD.
Koelreuteria henryi Dummer, an endemic plant of Taiwan, has been used as a folk medicine for the treatment of hepatitis, enteritis, cough, pharyngitis, allergy, hypertension, hyperlipidemia, and ...cancer. Austrobailignan-1, a natural lignan derivative isolated from Koelreuteria henryi Dummer, has anti-oxidative and anti-cancer properties. However, the effects of austrobailignan-1 on human cancer cells have not been studied yet. Here, we showed that austrobailignan-1 inhibited cell growth of human non-small cell lung cancer A549 and H1299 cell lines in both dose- and time-dependent manners, the IC50 value (48 h) of austrobailignan-1 were 41 and 22 nM, respectively. Data from flow cytometric analysis indicated that treatment with austrobailignan-1 for 24 h retarded the cell cycle at the G2/M phase. The molecular event of austrobailignan-1-mediated G2/M phase arrest was associated with the increase of p21Waf1/Cip1 and p27Kip1 expression, and decrease of Cdc25C expression. Moreover, treatment with 100 nM austrobailignan-1 for 48 h resulted in a pronounced release of cytochrome c followed by the activation of caspase-2, -3, and -9, and consequently induced apoptosis. These events were accompanied by the increase of PUMA and Bax, and the decrease of Mcl-1 and Bcl-2. Furthermore, our study also showed that austrobailignan-1 was a topoisomerase 1 inhibitor, as evidenced by a relaxation assay and induction of a DNA damage response signaling pathway, including ATM, and Chk1, Chk2, γH2AX phosphorylated activation. Overall, our results suggest that austrobailignan-1 is a novel DNA damaging agent and displays a topoisomerase I inhibitory activity, causes DNA strand breaks, and consequently induces DNA damage response signaling for cell cycle G2/M arrest and apoptosis in a p53 independent manner.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present prenatal diagnosis and molecular cytogenetic characterization of de novo distal 5p deletion and distal 22q duplication.
A 34-year-old woman was underwent amniocentesis at 17 weeks of ...gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 5 der(5) with an abnormal distal 5p segment of unknown origin. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis was performed on the cultured amniocytes, and the result was arr 5p15.33p13.3 (22,149–29,760,922) × 1.0, arr 22q13.2q13.33 (42, 192, 065–51,178,264) × 3.0 GRCh37 (hg19) with a 29.739-Mb deletion of 5p15.33-p13.3 encompassing 55 Online Mendelian Inheritance in Man (OMIM) genes including TPPP, TERT, SRD5A1, SEMA5A and CTNND2, and an 8.986-Mb duplication of 22q13.2-q13.33 encompassing 82 OMIM genes including TRMU, SCO2, TYMP, CPT1B and SHANK3. The fetal karyotype was 46,XY,der(5)t(5; 22)(p13.3; q13.2)dn. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Postnatal polymorphic DNA marker analysis confirmed a maternal origin of the aberrant chromosome 5.
aCGH and polymorphic DNA marker analyses can determine the nature and parental origin of the de novo chromosome aberration, and the information acquired is useful for genetic counseling.
•A novel vision-based framework for 3D hand pose estimation is proposed.•A spherical Part Model is proposed to transform the joint locations to an explicit representation.•The dataset is expanded by ...rotating the original images every 45°.
Hand pose estimation is a hot topic in recent years. It has been widely used in virtual reality since it provides an interface for communication between human and cyberspace. Hand pose estimation is difficult due to some challenges. First, we need to detect human hand which is very changeable. Second, the high degree of freedom leads to difficulties in pose estimation. In this paper, we aim to build a hand pose estimation system which can correctly detect human hand and estimate its pose. We design a model called spherical part model (SPM) and train a deep convolutional neural network using this model. As a result, our network can more accurately estimate hand pose based on prior knowledge of human hand. To demonstrate it, a complete experiment is conducted on two public and one self-build datasets. The results show that our system can outperform other state of the art works.
Ischemic cardiac or cerebrovascular disease (ICCD) survivors represent a subpopulation with a high cancer risk. Antiplatelet medications, such as aspirin, remain a fundamental therapy for the ...secondary prevention of ischemic attack in these patients. We conducted a population-based cohort study to investigate the association of long-term low-dose aspirin use with the risk of primary cancer in ICCD survivors. Patients aged ≥20 years with newly diagnosed ICCD (n = 98,519) between January 2000 and December 2013 were identified from the Taiwan National Health Insurance Research Database. The aspirin user and nonuser groups (each n = 24,030) were propensity-matched (1:1) for age, sex, comorbidities, prior medications, ICCD diagnosis year, and year of index dates. The incidence rate of primary cancer was significantly lower in the user group (6.49/1000 person-years) than in the nonuser group (14.04/1000 person-years). Multivariate Cox regression analysis indicated that aspirin use was an independent factor associated with a reduced risk of primary cancer (aHR (95% confidence interval) = 0.42 (0.38−0.45)) after adjustment. Kaplan−Meier curve analysis revealed that the cumulative incidence rate of primary cancer was significantly lower (p < 0.0001) in the user group than in the nonuser group over the 14-year follow-up period. Subgroup analyses demonstrated that this anticancer effect increased with duration of treatment and with similar estimates in women and men. In addition, aspirin use was associated with a reduced risk for seven out of the ten most common cancers in Taiwan. These findings suggest the anticancer effect of aspirin in ICCD survivors and provide information for assessing the benefit-to-risk profile of aspirin as an antiplatelet medication in these patients.
Titanium nitride (TiN) is an ideal material for infrared plasmonics due to its excellent optical properties, high melting temperature, mechanical and chemical stabilities, and bio- and CMOS ...compatibilities. In this work, we demonstrate that ultrathin and scalable TiN epitaxial structures can be applied for tunable infrared plasmonics, extending into near- to mid-infrared spectral regions. The ultrathin (111)-oriented TiN epitaxial films studied here were grown on c-plane sapphire wafers without any wetting layer by ultrahigh-vacuum nitrogen-plasma-assisted molecular-beam epitaxy. This method allows for stoichiometric TiN growth without the issue of contamination (especially oxygen) in conventional TiN growth techniques. Structural analyses for these films validate their single-crystalline properties with continuous film morphologies down to a few nanometers in thickness. Furthermore, the frequency-tunable (wavelength range: 1–4 μm) plasmonic metasurfaces have been demonstrated by controlling surface plasmon resonances via lithographically patterning of ultrathin TiN epitaxial films with varying thicknesses (4–30 nm) and grating structure parameters (pitch: 300–1200 nm, width: 200–800 nm). The tunable plasmonic metasurfaces based on ultrathin TiN epitaxial films hold great promise for emerging infrared plasmonic applications, such as thermal photovoltaics requiring narrow-band emitters, photodetectors, and biosensors in the near- and mid-infrared spectral regions.
To evaluate the correlation of high levels >2.0 multiples of median (MoM) of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome.
We retrospectively studied 6245 ...pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks’ gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes.
Among the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case).
A high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.
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