Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose ...was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han‐Chinese patients without prior warfarin treatments. Using the genotype‐based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR >4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R2 of 0.62). This study demonstrated that pharmacogenetics‐based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.
Clinical Pharmacology & Therapeutics (2008); 84, 1, 83–89 doi:10.1038/sj.clpt.6100453
In this prospective study, Han Chinese subjects who were candidates for carbamazepine therapy were screened for the HLA-B*1502 allele because of its association with the Stevens–Johnson syndrome and ...toxic epidermal necrolysis.
The Stevens–Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are two of the most serious adverse reactions caused by drugs. SJS is characterized by high fever, malaise, and a rapidly developing, blistering exanthema of macular papules and target-like lesions, accompanied by mucosal involvement. This condition is associated with a rate of death of approximately 5%. TEN has a similar presentation, with even more extensive skin detachment and a death rate of 25 to 35%.
1
Carbamazepine, an anticonvulsant and specific analgesic agent for trigeminal neuralgia, is the most common cause of SJS–TEN in Southeast Asian countries.
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We previously . . .
ABSTRACT
Observations in the local universe show a tight correlation between the masses of supermassive black holes (SMBHs; MBH) and host-galaxy bulges (Mbulge), suggesting a strong connection ...between SMBH and bulge growth. However, direct evidence for such a connection in the distant universe remains elusive. We have studied sample-averaged SMBH accretion rate ($\overline{\rm BHAR}$) for bulge-dominated galaxies at z = 0.5–3. While previous observations found $\overline{\rm BHAR}$ is strongly related to host-galaxy stellar mass (M⋆) for the overall galaxy population, our analyses show that, for the bulge-dominated population, $\overline{\rm BHAR}$ is mainly related to SFR rather than M⋆. This ${\overline{\rm BHAR}}$–SFR relation is highly significant, e.g. 9.0σ (Pearson statistic) at z = 0.5–1.5. Such a $\overline{\rm BHAR}$–SFR connection does not exist among our comparison sample of galaxies that are not bulge dominated, for which M⋆ appears to be the main determinant of SMBH accretion. This difference between the bulge-dominated and comparison samples indicates that SMBHs only coevolve with bulges rather than the entire galaxies, explaining the tightness of the local MBH−Mbulge correlation. Our best-fitting ${\overline{\rm BHAR}}$–SFR relation for the bulge-dominated sample is ${\log \overline{\rm BHAR}= \log \mathrm{SFR} - (2.48\pm 0.05)}$ (solar units). The best-fitting $\overline{\rm BHAR}/\mathrm{SFR}$ ratio (10−2.48) for bulge-dominated galaxies is similar to the observed MBH/Mbulge values in the local universe. Our results reveal that SMBH and bulge growth are in lockstep, and thus non-causal scenarios of merger averaging are unlikely the origin of the MBH−Mbulge correlation. This lockstep growth also predicts that the MBH−Mbulge relation should not have strong redshift dependence.
Abstract Internet addiction is a newly emergent disorder. It has been found to be associated with a variety of psychiatric disorders. Information about such coexisting psychiatric disorders is ...essential to understand the mechanism of Internet addiction. In this review, we have recruited articles mentioning coexisting psychiatric disorders of Internet addiction from the PubMed database as at November 3, 2009. We describe the updated results for such disorders of Internet addiction, which include substance use disorder, attention-deficit hyperactivity disorder, depression, hostility, and social anxiety disorder. We also provide discussion for possible mechanisms accounting for the coexistence of psychiatric disorders and Internet addiction. The review might suggest that combined psychiatric disorders mentioned above should be evaluated and treated to prevent their deteriorating effect on the prognosis of Internet addiction. On the other hand, Internet addiction should be paid more attention to when treating people with these coexisting psychiatric disorders of Internet addiction. Additionally, we also suggest future necessary research directions that could provide further important information for the understanding of this issue.
Abstract
Various methods of evaluating a humectant’s moisture retention have unique mechanisms. Hence, for designing advanced or efficient ingredients of cosmetic products, a clear understanding of ...differences among methods is required. The aim of this study was to analyze the moisture-retention capacity of glycerin, a common ingredient in cosmetic products. Specifically, this study applied gravimetric analysis, transepidermal water loss (TEWL) analysis, and differential scanning calorimetry (DSC) to examine the evaporation of glycerin solutions of different concentrations. The results revealed that the moisture-retention capacity of glycerin increased with the glycerin concentration from 0 to 60 wt%, and glycerin at concentration of 60–70 wt% did not exhibit weight change during the evaporation process. When the glycerin concentration exceeded 70 wt%, moisture sorption occurred in the glycerin solution. Furthermore, the results revealed a deviation between the evaporation rates measured using gravimetric analysis and those measured using TEWL analysis. However, normalizing the results of these analyses yielded the relative evaporation rates to water, which were consistent between these two analyses. DSC thermograms further confirmed the consistent results and identified two hydrated water microstructures (nonfreezable water and free water) in the glycerin solutions, which explained why the measured evaporation rate decreased with the glycerin concentration. These findings can be applied to prove the moisture-retention capacity of a humectant in cosmetic products by different measuring methods.
With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a ...prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk.
This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers.
The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither.
Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.
Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin ...of cosmological FRBs is still not settled. Here we report the detection of1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.9). These observations show irregular short-time variation ofthe Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth-Sun distance) ofthe source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.
Efficient organic light‐emitting diodes (OLEDs) incorporating IrIII bis(4,6‐difluorophenylpyridinato)‐3‐(trifluoromethyl)‐5‐ (pyridin‐2‐yl)‐1,2,4‐triazolate (FIrtaz) and IrIII ...bis(4,6‐difluorophenylpyridinato)‐5‐(pyridin‐2‐yl)‐1H‐tetrazolate (FIrN4) demonstrate higher‐purity blue‐light emission than the long‐known IrIII bis(4,6‐difluorophenylpyridinato)picolate (FIrpic) phosphorophore. New host materials with higher glass‐transition temperatures were also found to enhance the OLED performance.
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