Objective UGT2B7 plays a central role in the liver-mediated biotransformation of endogenous and exogenous compounds. The genetic basis of interindividual variability in UGT2B7 function is unknown. This study aimed to discover novel gene variants of functional significance. Methods Caucasian human livers (n=54) were used. UGT2B7 was resequenced in 12 samples (6 highest and 6 lowest for the formation of morphine-3-glucuronide, M3G). Haplotype-tagging single nucleotide polymorphisms (tSNPs) were genotyped in the entire sample set. Samples were phenotyped for mRNA expression. Results 10 tSNPs were identified and their haplotypes were inferred. Haplotype 4 (-45597G;-6682_-6683A;372A;IVS1+9_IVS1+10A;IVS1+829T;IVS1+985G;IVS1+999C;IVS1+1250G;80 1T;IVS4+185C) (frequency of 0.12) was associated with an increase in enzyme activity and gene expression. The 1/4 and 4/6 diplotypes had higher M3G formation compared to 1/1 (p<0.05) and 2/3 (p<0.01) diplotypes. Diplotypes containing haplotype 4 resulted in a significant 45% average increase in the formation of M3G compared to diplotypes without haplotype 4 (p=0.002). There was also an association between haplotype 4 and increased mRNA expression. IVS1+985A>G, 735A>G and 1062C>T are the putative functional variants of haplotype 4. We also identified two mRNA splicing variants (UGT2B7_v2 and UGT2B7_v3) splicing out exon 1, 4, 5 and 6 but sharing exons 2 and 3 with the involvement of additional 5' exons. UGT2B7_v2 was detected in all livers tested, but UGT2B7_v3 was present at much lower levels compared to UGT2B7_v2. The UGT2B7 reference sequence mRNA is now named UGT2B7_v1. Conclusions UGT2B7 haplotype 4 is functional and its effects on the biotransformation of UGT2B7 substrates should be tested in controlled clinical trials. Biochemical studies should investigate the functional role of the newly discovered mRNA splicing variants.

The purpose of this study was to investigate the potential mechanisms behind the blood flow restriction (BFR) stimulus in the absence of exercise. Nine participants completed a 10 minute time control and then a BFR protocol. The protocol was five, 5-minute bouts of inflation with 3-minutes of deflation between each bout. The pressure was set relative to each individual's thigh circumference. Significant increases in muscle thickness were observed for both the vastus lateralis (VL) [6%, p = 0.027] and rectus femoris (RF) [22%, p = 0.001] along with a significant decrease in plasma volume [15%, p = 0.001]. Ratings of discomfort during the BFR protocol peaked at 2.7 (light discomfort). There were no significant changes with whole blood lactate, electromyography (EMG), or heart rate (HR), however, there was a trend for a significant increase in HR during the 5th inflation (p = 0.057). In conclusion, this is the first study to demonstrate that the attenuation of both muscle atrophy and declines in strength previously observed with brief applications of BFR may have been mediated through an acute fluid shift induced increase in muscle size. This is supported by our finding that the changes in muscle thickness are maintained even after the cuffs have been removed.

Discrepancies exist whether blood flow restriction (BFR) exacerbates exercise-induced muscle damage (EIMD). This study compared low-intensity eccentric contractions of the elbow flexors with and without BFR for changes in indirect markers of muscle damage. Nine untrained young men (18-26 y) performed low-intensity (30% 1RM) eccentric contractions (2-s) of the elbow flexors with one arm assigned to BFR and the other arm without BFR. EIMD markers of maximum voluntary isometric contraction (MVC) torque, range of motion (ROM), upper arm circumference, muscle thickness and muscle soreness were measured before, immediately after, 1, 2, 3, and 4 days after exercise. Electromyography (EMG) amplitude of the biceps brachii and brachioradialis were recorded during exercise. EMG amplitude was not significantly different between arms and did not significantly change from set 1 to set 4 for the biceps brachii but increased for the brachioradialis (p ≤ 0.05, 12.0% to 14.5%) when the conditions were combined. No significant differences in the changes in any variables were found between arms. MVC torque decreased 7% immediately post-exercise (p ≤ 0.05), but no significant changes in ROM, circumference, muscle thickness and muscle soreness were found. These results show that BFR does not affect EIMD by low-intensity eccentric contractions.

Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen.

Different hepatitis C virus (HCV) genotypes exhibit differences in disease pathogenesis and progression, as well as disease outcomes and response to therapy. Tracking the change of HCV genotypes in various epidemiological settings is critical for both disease surveillance and the development of improved antiviral treatment. Here, we tracked the changes in the prevalence of the HCV genotypes in China between 2004-2007 and 2008-2011. HCV-RNA-positive sera were collected from volunteer blood donors during the period 2008-2011. The genotypes were determined by phylogenic analysis using the NS5B and E1 sequences. Geographical and demographic distribution patterns related to the HCV genotypes obtained in 2008-2011 were compared with our previous study, which recorded data in the period 2004-2007. Pearson chi-square test and t-test were used to statistically analyze the results. In 2008-2011, HCV subtypes 1b and 6a were detected in 43.8 % (184/420) and 34.3 % (144/420), respectively. The male/female ratio was found to be higher for HCV genotype 6 than for genotypes 1 and 2. When compared with the period of 2004-2007, although no significant difference was found in gender or age for genotypes 1, 2, 3 and 6, the subtype 6a frequency was significantly increased from 11 % to 26.5 % in the blood donors from outside of Guangdong Province in 2008-2011. A pattern of increase in HCV subtype 6a was found in blood donors outside of Guangdong Province, indicating that HCV subtype 6a has rapidly spread from Guangdong to other regions of China over the past 10 years.Electronic supplementary materialThe online version of this article (doi:10.1007/s00705-014-2185-1) contains supplementary material, which is available to authorized users.