Genetic analysis of health traits and their associations with longevity, fertility, production, and conformation traits in Holstein cattle.

Health traits have high economic values in dairy cattle breeding, which can cause considerable financial loss through involuntary culling. In this study, fourteen health traits were analysed, including five composite health traits: reproductive disorders, udder health (UH), digestive disorders, metabolic disorders, locomotory diseases (LD), and nine independent health traits: gestation disorders and peripartum disorders, irregular estrus cycle and sterility, metritis (ME), mastitis (MA), abomasal displacement (AD), enteritis (EN), and ketosis, claw diseases (CD), laminitis complex. This study analysed variance components for health traits through both single and bivariate repeatability animal models. All health traits showed low heritability, ranging from 0.001 to 0.025. Most of the health traits in five categories showed negative genetic correlations, ranging from -0.012 (CD and EN) to -0.634 (ME and EN). Strong positive genetic correlations appeared within the same category, ranging from 0.469 (EN and AD) to 0.994 (UH and MA, LD and CD). Furthermore, approximate genetic correlations were evaluated between health traits and routinely collected traits (longevity, fertility, production, and conformation). In general, the low to moderate approximate genetic correlations were estimated between health traits and routinely collected traits. The estimated correlations between health traits and longevity, fertility, production, and conformation traits could provide an indirect reference for disease-resistance breeding in Holstein cattle.

Genetic analysis of longevity and their associations with fertility traits in Holstein cattle.

The increase of longevity is intended to reduce involuntary culling rates, not extend the life span, and it reflects the ability of animals to successfully cope with the environment and disease during production. Sire model, animal model and repeatability animal models were used to estimate the (co) variance components of longevity and fertility traits. Six longevity and thirteen fertility traits were analysed, including herd life (HL), productive life (PL), number of days between first calving and the end of first lactation or culling (L1); number of days between first calving and the end of the second lactation or culling (L2); number of days between first calving and the end of the third lactation or culling (L3); number of days between first calving and the end of the fourth lactation or culling (L4); age at first service, age at first calving (AFC), the interval from first to last inseminations in heifer (IFLh), conception rate of first insemination in heifer, days open (DO), calving interval, gestation length, interval from calving to first insemination (ICF), interval from first to last inseminations in cow (IFLc), conception rate of first insemination in cow, calving ease (CE), birth weight, and calf survival. The estimated heritabilities (±SE) were 0.018 (±0.003), 0.015 (±0.003), 0.049 (±0.004), 0.025 (±0.003), 0.009 (±0.002) and 0.011 (±0.002) for HL, PL, L1, L2, L3 and L4, respectively. Strong correlations were appeared in HL and PL; the genetic and phenotypic correlation coefficients were 0.998 and 0.985, respectively. There were high genetic and phenotypic correlations which were observed in L1 and L2, L2 and L3, L3 and L4, respectively. All fertility traits of heifer showed medium to high heritability, while the cow showed low heritability. All heifer fertility traits had low genetic associations with longevity traits, ranging from -0.018 (L2 and IFLh) to 0.257 (L3 and AFC). Most of the fertility traits showed negative correlations with longevity traits in different parities, and we recommend DO, ICF, IFLc and CE as indirect indicators of longevity traits in dairy cows, but we also need to take into account the differences between parities.

Long non-coding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-1246.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-1246, by D. Lin, H.-P. Xu, J.-H. Lin, H.-H. Hu, Q. Wang, J. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5795-5801-DOI: 10.26355/eurrev_201907_18318-PMID: 31298331" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18318.

Overexpression of ACE2 prevents hypoxia-induced pulmonary hypertension in rats by inhibiting proliferation and immigration of PASMCs.

OBJECTIVE: Imbalance of the ratio of angiotensin converting enzyme (ACE) and ACE2 may lead to pathological conditions in lung. However, its effect on hypoxia-induced pulmonary hypertension (HPH) remains unclear. Therefore, the aim of this study was to investigate the effects of ACE2 overexpression on rat primary pulmonary arterial smooth muscle cells (PASMCs) and HPH rat model. MATERIALS AND METHODS: ACE and ACE2 expression in rat PASMCs under hypoxia condition, as well as in HPH rat model, was detected. The overexpressed ACE2 gene was transfected into PASMCs by Lentiviral. Later, the proliferation and migration of PASMCs were evaluated. Meanwhile, the overexpressed ACE2 gene was transfected into rats and exposed to hypoxia for four weeks. Finally, the right ventricular systolic pressure, the right ventricular hypertrophy, and the percentage of the medial wall thickness were measured to evaluate the development of HPH. RESULTS: Imbalance of the expression of ACE/ACE2 was indicated in rat PASMCs under hypoxia condition and in the HPH rat model, respectively. The overexpression of ACE2 significantly inhibited PASMCs proliferation and migration. Moreover, the overexpressed ACE2 could significantly attenuate pulmonary hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy in HPH rat model. CONCLUSIONS: ACE2 is related to the formation of pulmonary vascular remodeling and pulmonary hypertension. Furthermore, it may prevent hypoxia-induced pulmonary hypertension by inhibiting the proliferation of PASMCs.

Spiral T1 Spin-Echo for Routine Postcontrast Brain MRI Exams: A Multicenter Multireader Clinical Evaluation.

BACKGROUND AND PURPOSE: Spiral MR imaging has several advantages compared with Cartesian MR imaging that can be leveraged for added clinical value. A multicenter multireader study was designed to compare spiral with standard-of-care Cartesian postcontrast structural brain MR imaging on the basis of relative performance in 10 metrics of image quality, artifact prevalence, and diagnostic benefit. MATERIALS AND METHODS: Seven clinical sites acquired 88 total subjects. For each subject, sites acquired 2 postcontrast MR imaging scans: a spiral 2D T1 spin-echo, and 1 of 4 routine Cartesian 2D T1 spin-echo/TSE scans (fully sampled spin-echo at 3T, 1.5T, partial Fourier, TSE). The spiral acquisition matched the Cartesian scan for scan time, geometry, and contrast. Nine neuroradiologists independently reviewed each subject, with the matching pair of spiral and Cartesian scans compared side-by-side, and scored on 10 image-quality metrics (5-point Likert scale) focused on intracranial assessment. The Wilcoxon signed rank test evaluated relative performance of spiral versus Cartesian, while the Kruskal-Wallis test assessed interprotocol differences. RESULTS: Spiral was superior to Cartesian in 7 of 10 metrics (flow artifact mitigation, SNR, GM/WM contrast, image sharpness, lesion conspicuity, preference for diagnosing abnormal enhancement, and overall intracranial image quality), comparable in 1 of 10 metrics (motion artifacts), and inferior in 2 of 10 metrics (susceptibility artifacts, overall extracranial image quality) related to magnetic susceptibility (P < .05). Interprotocol comparison confirmed relatively higher SNR and GM/WM contrast for partial Fourier and TSE protocol groups, respectively (P < .05). CONCLUSIONS: Spiral 2D T1 spin-echo for routine structural brain MR imaging is feasible in the clinic with conventional scanners and was preferred by neuroradiologists for overall postcontrast intracranial evaluation.

Long non-coding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-1246.

OBJECTIVE: Recently, long non-coding ribonucleic acids (lncRNAs) have attracted more attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA MIAT in the progression of non-small cell lung cancer (NSCLC) and to explore the possible underlying mechanism. PATIENTS AND METHODS: MIAT expression in NSCLC tissue samples was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association between the expression of MIAT and the prognosis of NSCLC patients were explored. Furthermore, the wound healing assay and the transwell assay were conducted in vitro. In addition, the luciferase assay and the RNA immunoprecipitation assay (RIP) were used to elucidate the underlying mechanism. RESULTS: The MIAT expression in NSCLC tissues was significantly higher than that of the corresponding normal tissues. Meanwhile, the MIAT expression was associated with the overall survival time of NSCLC patients. The migration and invasion of cells were significantly promoted after MIAT was over-expressed in vitro. Meanwhile, the cell migration and cell invasion were obviously remarkedly inhibited after MIAT knock-down in vitro. Bioinformatics analysis predicted that microRNA-1246 (miR-1246) was as a novel target for MIAT. The expression of miR-1246 was significantly down-regulated or up-regulated after the overexpression or down-expression of MIAT, respectively. Further mechanism assays showed that miR-1246 was a direct target of MIAT in NSCLC. CONCLUSIONS: MIAT enhanced the NSCLC cell migration and invasion via targeting miR-1246, which might be a potential biomarker in NSCLC.

Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

A Spiral Spin-Echo MR Imaging Technique for Improved Flow Artifact Suppression in T1-Weighted Postcontrast Brain Imaging: A Comparison with Cartesian Turbo Spin-Echo.

BACKGROUND AND PURPOSE: A challenge with the T1-weighted postcontrast Cartesian spin-echo and turbo spin-echo brain MR imaging is the presence of flow artifacts. Our aim was to develop a rapid 2D spiral spin-echo sequence for T1-weighted MR imaging with minimal flow artifacts and to compare it with a conventional Cartesian 2D turbo spin-echo sequence. MATERIALS AND METHODS: T1-weighted brain imaging was performed in 24 pediatric patients. After the administration of intravenous gadolinium contrast agent, a reference Cartesian TSE sequence with a scanning time of 2 minutes 30 seconds was performed, followed by the proposed spiral spin-echo sequence with a scanning time of 1 minutes 18 seconds, with similar spatial resolution and volumetric coverage. The results were reviewed independently and blindly by 3 neuroradiologists. Scores from a 3-point scale were assigned in 3 categories: flow artifact reduction, subjective preference, and lesion conspicuity, if any. The Wilcoxon signed rank test was performed to evaluate the reviewer scores. The t test was used to evaluate the SNR. The Fleiss κ coefficient was calculated to examine interreader agreement. RESULTS: In 23 cases, spiral spin-echo was scored over Cartesian TSE in flow artifact reduction (P < .001). In 21 cases, spiral spin-echo was rated superior in subjective preference (P < .001). Ten patients were identified with lesions, and no statistically significant difference in lesion conspicuity was observed between the 2 sequences. There was no statistically significant difference in SNR between the 2 techniques. The Fleiss κ coefficient was 0.79 (95% confidence interval, 0.65-0.93). CONCLUSIONS: The proposed spiral spin-echo pulse sequence provides postcontrast images with minimal flow artifacts at a faster scanning time than its Cartesian TSE counterpart.

Cloning and transformation analysis of isoflavone synthase gene into Minshan Trifolium pratense.

The aim of this study was to clone the isoflavone synthase (IFS) gene and establish the recombinant Minshan Trifolium pratense. The IFS gene was cloned from the callus of Minshan T. pratense using reverse transcription-polymerase chain reaction. The plant expression vector pRI101-AN-IFS was constructed and introduced into Agrobacterium tumefaciens strain LBA4404, and then screened under cephalosporin. IFS expression was detected by reverse transcription-polymerase chain reaction. The IFS gene was cloned successfully. Sequence analysis indicated that IFS gene had high homology with similar genes from other plants. The IFS-overexpressing callus was obtained by introducing the LBA4404-harboring IFS-pRI101-AN-IFS vector into T. pratense calluses.

The association of family social support, depression, anxiety and self-efficacy with specific hypertension self-care behaviours in Chinese local community.

This study aimed to test the role of family social support, depression, anxiety and self-efficacy on specific self-care behaviours. In a local community health center, 318 patients with hypertension completed a questionnaire assessing self-care, family social support, depression, anxiety and self-efficacy in 2012. Each self-care behaviour was separately analyzed with logistic regression models. The mean score of perceived family social support for hypertension treatment was 20.91 (maximum=60). Adult children were identified as the primary support source. Approximately 22.3% and 15.4% of participants reported symptoms of anxiety and depression, respectively. Participants had moderately positive levels of confidence performing self-care (42.1±13.3 out of 60). After adjusting for demographic and health variables, a 10-unit increase in family social support increased the odds ratio (OR) of taking medication by 1.39 (95% confidence interval (CI) 1.03-1.87) and increased the OR for measuring blood pressure (BP) regularly by 1.33 (95% CI 1.02-1.74). Depression and anxiety were not associated with any self-care behaviours. A10-unit increase in self-efficacy increased the adjusted OR for performing physical exercise to 1.25 (95% CI 1.04-1.49). In conclusion, family social support was positively associated with medication adherence and regular BP measurement. Strategies to improve family social support should be developed for hypertension control, yet further prospective studies are needed to understand the effects of family social support, depression, anxiety and self-efficacy on self-care behaviours.

Identification of CYP2C19 inhibitors from phytochemicals using the recombinant human enzyme model.

The aim of the present study was to develop the recombinant insect cell-expressed protein as an in vitro model for inhibitors screening for human cytochrome P450 2C19 (CYP2C19), and to use the model to investigate the inhibition effect of three phytochemicals on CYP2C19 in vitro. Omeprazole was applied as the probe substrate. The estimated inhibitory constant (K(i)) of ticlopidine and fluvoxamine were 0.64 +/- 0.025 microM and 0.29 +/- 0.090 microM, respectively. After co-incubation with ticlopidine or fluvoxamine, the mean omeprazole Michaelis-Menten constant (K(m)) increased from 4.99 +/- 0.22 microM to 16.25 +/- 1.22 microM or 19.20 +/- 1.73 microM, respectively, while omeprazole's mean V(max) did not vary much. Both ticlopidine and fluvoxamine were competitive inhibitors of CYP2C19. The IC50 of three phytochemicals, isoalantolactone, curcumol and schisandrin A was determined as 38.91 microM, 121.0 microM and 86.41 microM, and the K(i) as 5.02 +/- 1.04 microM, 35.84 +/- 8.95 microM, and 4.46 +/- 0.017 microM, respectively. The in vitro model for inhibitor screening established using recombinant CYP2C19 could be used to assess the inhibition potential of drug candidates. Isoalantolactone and schisandrin A are potent inhibitors of CYP2C19, while curcumol is a moderate potent inhibitor of CYP2C19.

A village-based multidisciplinary study on factors affecting the intensity of cystic echinococcosis in an endemic region of the Tibetan plateau, China.

SUMMARY: We investigated and quantified the factors which may affect the prevalence of cystic echinococcosis caused by Echinococcus granulosus in Rangtang County using a multidisciplinary approach. From a previously performed field survey, epidemiological data were linked with environmental data. Altitude and land surface temperature were extracted from remote-sensing images. Cumulative logistic regression models were used to identify and quantify the potential risk factors. The multiple regression models confirmed that yaks (χ 2 = 4·0447, P = 0·0443), dogs (χ 2 = 8·3455, P = 0·0039) and altitude (χ2 = 7·6223, P = 0·0058) were positively correlated with the prevalence of cystic echinococcosis, while land surface temperature may have a negative association. The findings showed that dogs and yaks play the most important role in the transmission of cystic echinococcosis, while altitude and land surface temperature may also be involved in the transmission.

Construction and application of double-transfected cells expressing the human transporter P-glycoprotein and cytochrome P450 3A4.

Intestinal P-glycoprotein (P-gp) and cytochrome P450 (CYP) enzymes are known to influence oral bioavailabilities of drugs. Recombinant plasmids pcDNA3.1/Hypgro/CYP3A4 were transfected into MDCK and MDCK-MDR1 cells to construct the single-transfected cell line MDCK-CYP3A4 and double-transfected cell line MDCK-MDR1/CYP3A4. The expression of CYP3A4 in the double-transfected cell line was determined by Western blot and its activity was detected by the metabolism assays of three substrates of CYP3A4, which were 7-benzyloxy-4-trifluoro-methylcoumarin (BFC), testosterone and midazolam. In addition, the selection of monoclones with high CYP3A4 activities in the single-tranfected cell line was performed by the P450 Glo CYP3A4 assay. Through MTT assay, the interaction between P-gp and CYP3A4 was preliminarily determined based on the changes of IC50 values. The results showed that paclitaxel detoxified in the single-transfected MDCK-MDR1 cell because of P-gp efflux. And it was also less toxic in the single-transfected CYP3A4 cell line due to the metabolism by CYP3A4. In the double-transfected MDCK-MDR1/CYP3A4 cell line, the toxicity decreased dramatically because of the interplay between P-gp and CYP3A4. Therefore, the cell model could be applied to study the toxicity and detoxification of chemicals due to the metabolism by CYP3A4 and the efflux through P-gp.

Quantitative proton MR techniques for measuring fat.

Accurate, precise and reliable techniques for the quantification of body and organ fat distributions are important tools in physiology research. They are critically needed in studies of obesity and diseases involving excess fat accumulation. Proton MR methods address this need by providing an array of relaxometry-based (T1, T2) and chemical shift-based approaches. These techniques can generate informative visualizations of regional and whole-body fat distributions, yield measurements of fat volumes within specific body depots and quantify fat accumulation in abdominal organs and muscles. MR methods are commonly used to investigate the role of fat in nutrition and metabolism, to measure the efficacy of short- and long-term dietary and exercise interventions, to study the implications of fat in organ steatosis and muscular dystrophies and to elucidate pathophysiological mechanisms in the context of obesity and its comorbidities. The purpose of this review is to provide a summary of mainstream MR strategies for fat quantification. The article succinctly describes the principles that differentiate water and fat proton signals, summarizes the advantages and limitations of various techniques and offers a few illustrative examples. The article also highlights recent efforts in the MR of brown adipose tissue and concludes by briefly discussing some future research directions.

Reversal of ophthalmic artery flow as a predictor of intracranial hemodynamic compromise: implication for prognosis of severe carotid stenosis.

BACKGROUND AND PURPOSE: High-grade cervical carotid stenosis (70-99%) or occlusion often accompanies reversed ophthalmic artery flow (ROAF), but its potential clinical significances remain poor understood. This study assessed ROAF and the related variables caused by carotid hemodynamic compromise in patients with unilateral severe cervical carotid stenosis. METHODS: The study consisted of 200 patients diagnosed as unilateral high-grade cervical carotid stenosis/occlusion using ultrasonography. The hemodynamic parameters of 152 patients, excluding 48 with cervical carotid occlusion, were compared based on the presence of ROAF. Out of 200 patients, 159 underwent brain magnetic resonance imaging and were analysed for risk factors impacting functional outcomes including ROAF. RESULTS: The patients (n = 48) with internal carotid artery occlusion had significantly higher incidence (62.5%) of ROAF compared with that of 25.0% in those patients (n = 152) with unilateral high-grade carotid stenosis (P < 0.001). In ROAF patients (n = 38) with the unilateral high-grade stenosis, a significant retrobulbar arteries hemodynamic difference was observed between the stenotic and non-stenotic vessels. The patients (n = 159) with history of stroke (P = 0.035), ROAF (P = 0.023) and intracranial stenosis (P < 0.001) exhibited significantly higher incidence of poor functional outcome compared with the corresponding control groups. In the same patients (n = 159), those with both cervical and intracranial stenosis showed sevenfold higher risk (OR, 7.60; 95% CI, 3.44-16.81) for ROAF than those with only cervical stenosis. CONCLUSIONS: ROAF may result from intracranial hemodynamic compromise. Patients with unilateral high-grade cervical carotid stenosis/occlusion in combination with intracranial stenosis appear to be a significant risk factor for poor functional outcome and increased incidence of ROAF.

Cerebral hemodynamics and baroreflex sensitivity after carotid artery stenting.

OBJECTIVES: The long-term hemodynamic effects of carotid angioplasty and stenting (CAS) are unclear. We performed a longitudinal study to investigate the variations in cerebral hemodynamics in patients undergoing CAS. MATERIALS AND METHODS: We performed prospective evaluation of 63 symptomatic male patients (19 patients had transient ischemic attack and 44 had minor stroke; mean age: 77.3 ± 6.3 years [range: 51-86]). The mean blood flow velocities (MBFV) and pulsatility index (PI) of the middle cerebral arteries (MCA) on both sides were evaluated using transcranial color-coded Doppler (TCCD) ultrasonography. Cardiac autonomic activities were evaluated by measuring baroreflex sensitivity (BRS). All parameters were measured at baseline prior to CAS and at 1, 3, 6, and 12 months after CAS. RESULTS: The preoperative MBFV and PI of the ipsilateral MCA were significantly lower than those of the contralateral side. However, after CAS, MBFV in the ipsilateral MCA increased significantly until 2 weeks after stenting, after which the MBFV gradually decreased and remained stable for 1 year after CAS. Further, we observed a nonsignificant increase in MBFV in the contralateral MCA after CAS. In contrast to the MBFV, the BRS values decreased significantly 1 month after stenting and returned to baseline levels 6 months after CAS. CONCLUSIONS: Patients with CAS showed improved global cerebral hemodynamic status. However, the BRS did not normalize initially, and baseline value was achieved at 6 months after stenting.

Adiposity in children and adolescents: correlates and clinical consequences of fat stored in specific body depots.

The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on the laboratory and clinical assessment of depot-specific adiposity in children and adolescents, (ii) understand the variation in depot-specific adiposity and related health outcomes associated with age, sex, maturation, ethnicity and other factors and (iii) identify opportunities for incorporating new markers of abdominal obesity into clinical practice guidelines for obesity in children and adolescents. This symposium provided an overview of important new advances in the field and identified directions for future research. The long-term goal of the symposium is to aid in the early identification of children and adolescents who are at increased health risk because of obesity and obesity-related conditions.

Comparison of catalytical activity and stereoselectivity between the recombinant human cytochrome P450 2D6.1 and 2D6.10.

Polymorphisms of the cytochrome P450 2D6 (CYP2D6) gene play a major role in pharmacokinetic variability in human, while CYP2D6*10 is an important subtype in Asian people. In this study, the co-expression enzyme of human recombinant CYPOR, CYPb5 and CYP2D6.1 or CYP2D6.10 with the Bac-to-Bac system in baculovirus-infected insect cells was used to study the catalytical activity to imipramine metabolism and stereoselective metabolism of propranolol. The metabolites of imipramine were identified of hydroxyl imipramine and desipramine by LC-MS/MS. There are some differences between CYP2D6.1 and CYP2D6.10 activity. The kinetics parameters K(m), V(max), and CL(int) are 11.77 +/- 0.91 micromol/L, 0.4235 +/- 0.05 nmol/nmol CYP2D6.1/min and 3.60 x 10(-5) ml/min/nmol CYP2D6.1 (n = 3) for CYP2D6.1, respectively, and 9.05 +/- 0.87 micromol/L, 0.42 +/- 0.03 nmol/nmol CYP2D6.10/min, and 4.60 x 10(-5) ml/min/nmol CYP2D6.10 (n = 3) for CYP2D6.10. For propranolol, two metabolites were identified to be hydroxyl and N-desisopropylation propranolol by LC-MS/MS. When the substrate concentration was 0.20 micromol/L, CYP2D6.1 and CYP2D6.10 exhibited significant stereoseletivity. Furthermore, enantioselective formation has been detected. Both of CYP2D6.1 and CYP2D6.10 produced more hydroxyl propranolol from the R-(+)-isomer than from the S-(-)-isomer while there was no obvious difference for N-desisopropylation propranolol production between R-(+)- and S-(-)- isomer. In summary, there is a somewhat different catalytical activity and stereoselectivity between the human recombinant CYP2D6.1 and CYP2D6.10. The data we got will be helpful in preclinical research and clinical use of CYP2D6 substrates.

Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study.

Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 min of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after 10 weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest that physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization.

Stenting versus medical treatment for severe symptomatic intracranial stenosis.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is especially prevalent in Asians, but intracranial stent placement and medical treatment for severe intracranial stenosis are controversial. Thus, we compared long-term outcomes of these 2 therapeutic approaches in an Asian population. MATERIALS AND METHODS: Patients with angiographically proved severe (≥70%) symptomatic intracranial atherosclerosis, with or without stent placement, were retrospectively reviewed at a single center between 2002 and 2009, with adjustments for age, sex, vascular risk factors, degree of baseline stenosis, and baseline functional status. RESULTS: Of the 114 patients followed from 3 to 36 months (mean, 17.3 months) after initial diagnosis, 53 received 56 stents in addition to medical treatment (stent-placement group), and 61 matched patients received only medical treatment (medical group). Total clinical events, including stroke, TIA, and vascular death, were 12 (22.6%) and 15 (24.6%) in the stent-placement and medical groups, respectively (P = .99). The stent-placement group had significantly better functional outcomes than the medical group (94.3% versus 78.7% for mRS scores of 0-3, P = .045). Most events in the stent-placement group occurred within the first week of the periprocedural period (17.0%) as minor embolic or perforator infarctions, and the rate of events decreased thereafter (5.7%, P = .07). Stent placement over the perforator-rich MCA and BA independently predicted periprocedural events on multivariate regression analysis. In the medical group, events increased in frequency (21.7%) and severity with time. CONCLUSIONS: Although the total ischemic event rate was similar in the 2 groups during a 3-year follow-up, the stent-placement group had a more favorable functional outcome despite minor periprocedural strokes.