Miracle-dz/UniFAR-FTUs huggingface dataset:
Stereoselective pharmacokinetics of oxybutynin and N-desethyloxybutynin in vitro and in vivo

In vitro studies and the multiple applications of an oxybutynin (OXY) transdermal delivery system to Japanese healthy volunteers were conducted to characterize the stereoselectivity in the pharmacokinetics of OXY and its metabolite, N-desethyloxybutynin (DEOB). In human liver microsomes, (R)-OXY and (R)-DEOB were eliminated slightly slower than the corresponding (S)-enantiomers. The production of DEOB from OXY for the (R)-enantiomer was also slower than that for the (S)-enantiomer. In human P450-expressing liver microsomes, OXY was metabolized mainly by CYP3A4 among five cytochrome P450s (CYPs) tested (CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5) and the kinetics were slightly different for the enantiomer. The unbound fraction of (R)-OXY in plasma was almost two times higher than that of (S)-OXY, whereas (R)-DEOB was bound to plasma protein more than (S)-DEOB. No differences were observed in the blood–plasma concentration ratios for the enantiomers. After multiple applications of the transdermal delivery system, the plasma concentrations of (R)-OXY were lower than those of (S)-OXY. These data indicate that for the stereoselectivity of OXY, the unbound fraction of each OXY enantiomer was a major factor and the metabolism in liver had a minimal effect.
Association between vitamin‐D receptor gene FokI polymorphism and Graves' disease among Taiwanese Chinese

1,25(OH)2D3, exerting its biological effects through the vitamin‐D receptor (VDR), plays a role in the modulation of the human immune system. The aim of this study was to test for the presence of an association between VDR gene polymorphism and the susceptibility to Graves' disease (GD) for Taiwanese Chinese. Using a polymerase chain reaction (PCR)‐based restriction analysis, we screened the VDR exon 2 start codon T/C (VDR‐FokI) polymorphism to determine the genotypes for 88 GD patients and 90 normal controls. From the genotype analysis, GD patients featured a greater proportion of the CC genotype (44.3%) and a smaller proportion of the TT genotype (12.5%) than was the case for normal controls (CC: 23.3% and TT: 28.9%; chi‐squared test, P=0.003). The odds ratios (ORs) for the risk of the CC genotype's appearance compared with the corresponding values for the TT and TC genotypes, for the GD patient group, were, 4.39 (95% confidence interval [CI]: 1.82–10.61) and 2.10 (95% CI: 1.06–4.18), respectively. With respect to the allelic analysis, we observed significantly increased C‐allele (65.9%) and decreased T‐allele (34.1%) frequencies among GD patients compared to normal controls (C: 47.2% and T: 52.8%; chi‐squared test, P=0.002). The OR for the risk of appearance of the C allele in the GD‐patient group was 1.93 (95% CI: 1.27–2.95). In conclusion, the VDR‐FokI T/C polymorphism might be able to be used as a genetic marker to predict the likelihood of GD development. J. Clin. Lab. Anal. 21:173–177, 2007. © 2007 Wiley‐Liss, Inc.
Starch Microparticles as Oral Vaccine Adjuvant: Antigen-dependent Uptake in Mouse Intestinal Mucosa

An oral vaccine formulation comprised of starch microparticles with conjugated antigens is being developed. In this report we have examined the uptake of such microparticles by the intestinal mucosa and examined whether the conjugated antigen can influence the uptake. Two model antigens were used: recombinant cholera toxin B subunit (rCTB), which is known to bind to the ubiquitous GM1-receptor, and human serum albumin (HSA) which is not known to have any specific binding properties. The uptake was studied in mouse ligated intestinal loops into which the microparticles were injected. The intestinal loops were excised, fixed in ice-cold 95% ethanol. Entire specimens were mounted, exposed to fluorescence-labeled reagents staining the cytoskeleton, the particles and/or M cells and examined in a confocal laser-scanning microscope. A qualitative difference in the uptake of the rCTB- and HSA-conjugated microparticles was seen. The rCTB-conjugated microparticles were found both in villi and in the follicles of the Peyer's patches. HSA-conjugated microparticles could only be detected in the follicles of the Peyer's patches and not in villi. The rCTB conjugated to the microparticles did not lose its ability to bind the GM1-receptor, as shown with a GM1-ELISA, and the uptake of rCTB-conjugated microparticles in villi is most probably facilitated by the rCTB binding to the GM1-receptor. The qualitative difference in uptake could be of importance for the development of an immune response as the cytokine and chemokine microenvironment during antigen presentation will decide the differentiation of the immune response induced.
Lactate-induced vascular relaxation in porcine coronary arteries is mediated by Ca2+-activated K+ channels.

Under ischemic conditions and during strenuous exercise, lactate concentrations increase in coronary artery smooth muscle cells. Although lactate causes pH-independent vasorelaxation, the mechanisms responsible for this effect are unclear. We investigated the effect of lactate on K+ channels in smooth muscle cells from porcine coronary arteries. Neutralized lactate (3-100 mm) induced vasorelaxation in ring segments of porcine coronary arteries precontracted with KCl in a dose-dependent manner. One millimolar tetraethylammonium (TEA), an inhibitor of Ca2+-activated K+ channels (KCa channels), reversed the lactate-induced relaxation, while 60 microM glibenclamide, an inhibitor of ATP-sensitive K+ channels (KATP channels), did not. In both inside-out and cell-attached patch clamp technique with cultured smooth muscle cells, the KCa channels were activated by lactate. In inside-out patches, lactate activated KCa channels, even under acidic conditions. This is in contrast to the effect of H+ which inactivated KCa channels. We conclude that vasodilation of porcine coronary arteries induced by lactate is, at least in part, mediated by activation of KCa channels. This effect may be self-protective by maintaining coronary blood flow during ischemia.
Metal–Insulator–Silicon–Insulator–Metal Waveguide Splitters With Large-Arm Separation

Symmetric 1 × 2 splitters of metal-insulator-silicon-insulator-metal (MISIM) waveguides, which are hybrid plasmonic waveguides with a 190-nm-wide silicon strip covered by 30-nm-thick SiO2 and sandwiched by copper, are theoretically and experimentally investigated. The splitters consist of a Y-branch, two 90° submicrometer-radius bends (SRBs), and two straight MISIM waveguides connecting the Y-branch and the two SRBs. The Y-branch is an overlap of two oppositely directed SRBs. All the SRBs of the splitter have the same radius of curvature. The splitter has a feature that the length of the in-between MISIM waveguides is adjusted to make its input waveguide split over a short distance into its widely separated output waveguides. Simulation of the splitters indicates that the radius of curvature of the SRB needs to be ≥ 0.8 μm to make small the excess losses of the splitters. When the radius of curvature is 0.8 μm, the splitter which can connect its input waveguide just over 1.6 μm to its output waveguides spaced 6.4 μm apart has an excess loss of 1.4 dB. The splitters are realized by using the standard CMOS technology. The measured excess losses of the fabricated splitters are larger than the calculated excess losses. However, the measured dependence of the excess loss on the radius of curvature is similar to the calculated one. Finally, the splitter feature is theoretically confirmed, and the addition of a tapering region to the Y-branch is discussed to reduce the excess loss of the Y-branch.
Involvement of protoporphyrin IX accumulation in the pathogenesis of isoniazid/rifampicin-induced liver injury: the prevention of curcumin

Abstract Combination of isoniazid (INH) and rifampicin (RFP) causes liver injury frequently among tuberculosis patients. However, mechanisms of the hepatotoxicity are not entirely understood. Protoporphyrin IX (PPIX) accumulation, as an endogenous hepatotoxin, resulting from isoniazid and rifampicin co-therapy (INH/RFP) has been reported in PXR–humanized mice. Aminolevulinic acid synthase1 (ALAS1), ferrochelatase (FECH) and breast cancer resistance protein (BCRP) play crucial roles in PPIX synthesis, metabolism and transport, respectively. Herein, this study focused on the role of INH/RFP in these processes. We observed PPIX accumulation in human hepatocytes (L-02) and mouse livers. FECH expression was initially found downregulated both in L-02 cells and mouse livers and expression levels of ALAS1 and BCRP were elevated in L-02 cells after INH/RFP treatment, indicating FECH inhibition and ALAS1 induction might confer a synergistic effect on PPIX accumulation. Additionally, our results revealed that curcumin alleviated INH/RFP-induced liver injury, declined PPIX levels and induced FECH expression in both L-02 cells and mice. In conclusion, our data provide a novel insight in the mechanism of INH/RFP-induced PPIX accumulation and evidence for understanding pathogenesis of INH/RFP-induced liver injury, and suggest that amelioration of PPIX accumulation might be involved in the protective effect of curcumin on INH/RFP-induced liver injury.
The Relationship of Physical Function to Social Integration After Stroke

ABSTRACT Stroke is a leading cause of death and a serious long-term disability in this country. Much of the research on stroke rehabilitation has focused on physical/functional recovery as the predominant measure of outcome. There is a gap in knowledge of social issues and integration into societal, family, and community roles after stroke. A descriptive, correlational survey design was used to examine the relationships of functional status, depression, and overall stroke recovery to social integration in a convenience sample of ischemic stroke survivors. The survey response rate was 21.4%. Results showed that functional status, overall stroke recovery, and depression are highly significant predictors of social integration, explaining 62% of the variance (adjusted R2). Comorbid depression was negatively (−.74) and significantly (.01, two-tailed) correlated to social integration, such that higher levels of depression are associated with lower levels of social integration. Finally, employment status after stroke dropped from 48% to 4.2%, and poststroke employment status was correlated to social integration (significance = .03). Care for patients with chronic conditions like stroke should address all domains of the individual-physical, psychosocial, and environmental. Factors including depression and perceptions of overall stroke recovery are significant and should be addressed in the rehabilitation process to better promote social integration. Social integration is an important and understudied aspect of stroke recovery that warrants further research.
OPERA: responses to peginterferon and ribavirin therapy in a subgroup of interferon‐naïve patients with HIV/HCV genotype 2/3 co‐infection in Italy

Hepatitis C virus (HCV) genotype 3 (G3) is common among HIV/HCV co‐infected individuals and associated with moderate sustained virological response (SVR) rates with pegylated interferon (PEG‐IFN) plus ribavirin (RBV) therapy, while G2 is less frequent and associated with higher SVR. To determine SVR and other response rates, identify SVR predictors and analyse differences between G2 and G3 with PEG‐IFN/RBV in a large HIV/HCV G2/3 patient population.
Victims of criminal homicide in Sweden: a matched case-control study of health and social risk factors among all 1,739 cases during 1978-1994.

OBJECTIVE The psychiatric and medical characteristics of victims of homicide have not been systematically studied and are often confounded by race. This study was undertaken to determine health and social factors contributing to the risk of being murdered in the Swedish, predominantly Caucasian population. METHOD All 1,739 homicides between 1978 and 1994 in Sweden were studied in terms of variables in national case registers regarding health, crimes, immigration, and marital status. The same data were extracted for matched comparison persons in the general population, with controls for time of exposure. The data were analyzed by conditional logistic regression on matched pairs. RESULTS Traumatic brain injury, physical abuse, alcohol dependence, and criminal recidivism conferred risk of being murdered. CONCLUSIONS To the authors' knowledge, this is the first report of traumatic brain injury, in both men and women, as a risk factor for being murdered. Brain injury may mark risk-taking behavior in general or may cause provocative behavior.
Assessment of Birth Defects According to Maternal Therapy Among Infants in the Women and Infants Transmission Study

Background:To evaluate rate and types of birth defects according to timing of antiretroviral exposure among babies born to HIV-infected women. Methods:Anomalies identified during the prenatal, neonatal, or follow-up period were classified using criteria of the Antiretroviral Pregnancy Registry. Antiretroviral use was classified as none, second or third trimester only, or first trimester. Results:From January 1, 1990 through June 30, 2004, 2527 live births (LBs) occurred to 2353 women. Defects were identified in 90 babies for a rate of 3.56 defects per 100 LBs. The rate of defects was 3.19 per 100 LBs (24 of 752 LBs) with first-trimester antiretroviral exposure, 3.54 per 100 LBs (41 of 1158 LBs) with exposure later in pregnancy, and 4.05 of 100 LBs (25 of 617 LBs) with no antiretroviral use. Only genital abnormalities, specifically hypospadias, were significantly increased among babies born to women with first-trimester exposure to antiretrovirals (7 of 382 male LBs) compared with the 2 other groups (2 of 892 male LBs; P = 0.007). On logistic regression, use of zidovudine in the first trimester was associated with hypospadias (adjusted odds ratio = 10.68, 95% confidence interval: 2.11 to 54.13; P = 0.004). Conclusions:In general, data were reassuring, although the frequency of exposure to newer agents was limited. The increased risk of hypospadias after first-trimester exposure must be explored, because this association has not been detected previously.
An improved multi-objective optimization algorithm based on fuzzy dominance for risk minimization in biometric sensor network

Biometric system is very important for recognition in several security areas. In this paper we deal in designing biometric sensor manager by optimizing the risk. Risk is modeled as a multi-objective optimization with Global False Acceptance Rate and Global False Rejection Rate as two objectives. In practice, multiple biometric sensors are used and the decision is taken locally at each sensor and the data is passed to the sensor manager. At the sensor manager the data is fused using a fusion rule and the final decision is taken. The optimization involves designing the data fusion rule and setting the sensor thresholds. We have implemented a recent fuzzy dominance based decomposition technique for multi-objective optimization called MOEA/DFD and have compared its performance on other contemporary state-of-arts in multi-objective optimization field like MOEA/D, NSGAII. The algorithm introduces a fuzzy Pareto dominance concept to compare two solutions and uses the scalar decomposition method only when one of the solutions fails to dominate the other in terms of a fuzzy dominance level. We have simulated the algorithms on different number of sensor setups consisting of 3, 6, 8 sensors respectively. We have also varied the apriori probability of imposter from 0.1 to 0.9 to verify the performance of the system with varying threat. One of the most significant advantages of using multi-objective optimization is that with a single run just by changing the decision making logic applied to the obtained Pareto front one can find the required threshold and decision strategies for varying threat of imposter. But with single objective optimization one need to run the algorithms each time with change in threat of imposter. Thus multi-objective representation appears to be more useful and better than single objective one. In all the test instances MOEA/DFD performs better than all other algorithms.
Demographic and psychosocial correlates of sexual activity in older Chinese people.

AIMS AND OBJECTIVES This study examines sexual activity and associated psychosocial factors in older Chinese people. BACKGROUND Sexuality continues to play a pivotal role in our lives even as we grow old. There is, however, very limited research on the topic in older populations. DESIGN Cross-sectional survey. METHODS A representative sample of 688 older Chinese people (>60 years old) were individually interviewed on their demographic characteristics; their interest in, knowledge of and perceived control over sexual activities; and their engagement in sexual activity. RESULTS The results show that 51·32% of men and 41·26% of women reported engaging in some form of sexual activity. Sexual intercourse and caressing were commonly reported. A multiple regression analysis also showed that a higher level of sexual activity was associated with being younger, living with a spouse, having a strong interest in sex, having sufficient knowledge of elder sexuality and a high perceived control over sex. Distinct predictive factors in each gender were observed. A high level of perceived control was associated with a higher level of sexual activity in males but not females. A series of binary logistic regression analyses were conducted to determine the demographic and psychosocial correlates of sexual activity. With the exception of the use of objects (sex toys), sexual activities were consistently associated with being younger; living with a spouse; and having high levels of interest, knowledge and perceived control. CONCLUSIONS A sizable amount of older Chinese people engage in varying degrees of sexual activity, and most are still interested in sex. RELEVANCE TO CLINICAL PRACTICE Frontline health professionals need to be aware of the growing needs for sex education in older persons, particular attention should be paid to discuss the limitations brought about by various chronic conditions associated with ageing and their relevance to elder sexuality.
Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2.

BACKGROUND The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel-Lindau disease or multiple endocrine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measurements of plasma normetanephrine and metanephrine for detecting pheochromocytomas in patients with von Hippel-Lindau disease or MEN-2. METHODS We studied 26 patients with von Hippel-Lindau disease and 9 patients with MEN-2 who had histologically verified pheochromocytomas and 50 patients with von Hippel-Lindau disease or MEN-2 who had no radiologic evidence of pheochromocytoma. Von Hippel-Lindau disease and MEN-2 were diagnosed on the basis of germ-line mutations of the appropriate genes. The plasma concentrations of normetanephrine and metanephrine were compared with the plasma concentrations of catecholamines (norepinephrine and epinephrine) and urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid. RESULTS The sensitivity of measurements of plasma normetanephrine and metanephrine for the detection of tumors was 97 percent, whereas the other biochemical tests had a sensitivity of only 47 to 74 percent. All patients with MEN-2 had high plasma concentrations of metanephrine, whereas the patients with von Hippel-Lindau disease had almost exclusively high plasma concentrations of only normetanephrine. One patient with von Hippel-Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (<1 cm). The high sensitivity of measurements of plasma normetanephrine and metanephrine was accompanied by a high level of specificity (96 percent). CONCLUSIONS Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familial predisposition to these tumors.
Bacillus ectoiniformans sp. nov., a halotolerant bacterium isolated from deep-sea sediments.

A halotolerant, Gram-positive bacterium (strain NE-14T), which was isolated from sediment samples of the South China Sea, was subjected to a taxonomic study. Strain NE-14T grew well at wide temperature and pH ranges, 10.0-45.0 °C and pH 6-10, with an optimum at 30 °C and pH 8.0, respectively. Growth of strain NE-14T was observed at total salt concentrations of 0-10 % (w/v) with optimum at 2 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequence comparison indicated that the isolate belongs to the genus Bacillus. Strain NE-14T was related most closely to Bacillus shackletonii LMG 18435T, Bacillus bataviensis LMG 21833T, Bacillus idriensis SMC 4352-2T and Bacillus drentensis LMG 21831T with 16S rRNA gene sequence similarities of 96.2, 95.9, 95.8 and 95.7 %, respectively. DNA-DNA hybridization between strain NE-14T and B. shackletonii LMG 18435T, B. bataviensis LMG 21833T, B. idriensis SMC 4352-2T and B. drentensis LMG 21831T gave reassociation values of about 27.4, 22.4, 16.4 and 15.9 %, respectively. The DNA G+C content of strain NE-14T was 39.2 mol%. The predominant isoprenoid quinone was menaquinone 7 (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant cellular fatty acids of strain NE-14T were iso-C15 : 0 and anteiso-C15 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phospholipid. Based on the phenotypic and phylogenetic characteristics, it is proposed that strain NE-14T be classified as representing a novel species of the genus Bacillus, for which the name Bacillus ectoiniformans sp. nov. is proposed. The type strain is NE-14T ( = DSM 28970T = JCM 30397T).
Maternal serum levels of neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinase‐9 (MMP‐9) and their complex MMP‐9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study

The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase‐associated lipocalin (NGAL), matrix metalloproteinase‐9 (MMP‐9), and MMP‐9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA).