Factors Influencing Chinese Male's Willingness to Undergo Circumcision: A Cross-Sectional Study in Western China

BACKGROUND: Male circumcision (MC) has been shown to reduce the risk of female to male transmission of HIV. The goal of this survey was to explore the acceptability of MC among the Chinese and to identify factors associated with circumcision preference. METHODS: A cross-sectional survey was conducted between September 2009 and December 2010. We interviewed 2,219 male community participants, from three high HIV prevalence provinces in western China. A structured questionnaire was used to collect data on MC knowledge, willingness to accept MC, reasons to accept or refuse MC, and sexual behaviors and health. For those who refused MC, a health education intervention providing information on the benefits of circumcision was conducted. We used multiple logistic regression models to identify factors associated with the acceptability of MC. RESULTS: Of the respondents (n = 2,219), 44.6% (989/2,219) reported they would accept MC for the following reasons: promotion of female partners' hygiene (60.3%), redundant foreskin (59.4%), prevention of penile cancer (50.2%), enhanced sexual pleasure (41.4%), and protection against HIV and STDs (34.2%). The multivariable logistic regression showed that five factors were associated with MC willingness: long foreskin (OR = 15.98), residing in Xinjiang province (OR = 3.69), being younger than 25 (OR = 1.60), knowing hazards of redundant foreskin (OR = 1.78), and having a friend who underwent circumcision (OR = 1.36). CONCLUSION: The acceptability of male circumcision was high among the general population in China. Our study elucidates the factors associated with circumcision preference and suggests that more health education campaigns about positive health effects are necessary to increase the MC rate in China

A Better Anti-Diabetic Recombinant Human Fibroblast Growth Factor 21 (rhFGF21) Modified with Polyethylene Glycol

As one of fibroblast growth factor (FGF) family members, FGF21 has been extensively investigated for its potential as a drug candidate to combat metabolic diseases. In the present study, recombinant human FGF21 (rhFGF21) was modified with polyethylene glycol (PEGylation) in order to increase its in vivo biostabilities and therapeutic potency. At N-terminal residue rhFGF21 was site-selectively PEGylated with mPEG20 kDa-butyraldehyde. The PEGylated rhFGF21 was purified to near homogeneity by Q Sepharose anion-exchange chromatography. The general structural and biochemical features as well as anti-diabetic effects of PEGylated rhFGF21 in a type 2 diabetic rat model were evaluated. By N-terminal sequencing and MALDI-TOF mass spectrometry, we confirmed that PEG molecule was conjugated only to the N-terminus of rhFGF21. The mono-PEGylated rhFGF21 retained the secondary structure, consistent with the native rhFGF21, but its biostabilities, including the resistance to physiological temperature and trypsinization, were significantly enhanced. The in vivo immunogenicity of PEGylated rhFGF21 was significantly decreased, and in vivo half-life time was significantly elongated. Compared to the native form, the PEGylated rhFGF21 had a similar capacity of stimulating glucose uptake in 3T3-L1 cells in vitro, but afforded a significantly long effect on reducing blood glucose and triglyceride levels in the type 2 diabetic animals. These results suggest that the PEGylated rhFGF21 is a better and more effective anti-diabetic drug candidate than the native rhFGF21 currently available. Therefore, the PEGylated rhFGF21 may be potentially applied in clinics to improve the metabolic syndrome for type 2 diabetic patients

Saturated alanine scanning mutagenesis of the pneumococcus competence stimulating peptide identifies analogs that inhibit genetic transformation.

Antibiotic resistance is a major challenge to modern medicine. Intraspecies and interspecies dissemination of antibiotic resistance genes among bacteria can occur through horizontal gene transfer. Competence-mediated gene transfer has been reported to contribute to the spread of antibiotic resistance genes in Streptococcus pneumoniae. Induction of the competence regulon is mediated by a 17-amino acid peptide pheromone called the competence stimulating peptide (CSP). Thus, synthetic analogs that competitively inhibit CSPs may reduce horizontal gene transfer. We performed saturated alanine scanning mutagenesis and other amino acid substitutions on CSP1 to screen for analogs that disable genetic transformation in S. pneumoniae. Substitution of the glutamate residue at the first position created analogs that could competitively inhibit CSP1-mediated competence development in a concentration-dependent manner. Additional substitutions of the negatively-charged glutamate residue with amino acids of different charge, acidity and hydrophobicity, as well as enantiomeric D-glutamate, generated analogs that efficiently outcompeted CSP1, suggesting the importance of negative charge and enantiomericity of the first glutamate residue for the function of CSP1. Collectively, these results indicate that glutamate residue at the first position is important for the ability of CSP1 to induce ComD, but is dispensable for the peptide to bind the receptor. Furthermore, these results demonstrate the potential applicability of competitive CSP analogs to control horizontal transfer of antibiotic resistance genes in S. pneumoniae

Analyses of the ability of CSP1 analogs to induce <i>comX</i> expression and genetic transformation.

<p>Pneumococcal cells were incubated with CSP1 or with each analog at a final concentration of 100 ng/ml. The ability of each peptide to induce the competence regulon was measured by induction of the <i>comX</i> expression using the ß-galactosidase assays in D39pcomX::<i>lacZ</i> cells (A) or by genetic transformation using the <i>rpsL</i> gene in D39 cells (B). Transformants were selected on THB agar containing 100 µg/ml streptomycin. Experiments were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown.</p

Amino acid sequences of CSP1 and its analogs.

<p>Analogs were synthesized based on the sequence of CSP1 by alanine substitutions.</p

The negative charge and enantiomericity of glutamate residue in the first position is important for the activity of CSP1.

<p>(A) Amino acid substitutions of the first glutamate residue in CSP1. (B) Induction of <i>comX</i> expression by CSP1 analogs. D39pcomX::<i>lacZ</i> were incubated with CSP1 or with each glutamate substituted analog at a final concentration of 100 ng/ml. The ability of each peptide to induce the competence regulon was measured by induction of the <i>comX</i> by ß-galactosidase assays. (C) Genetic transformation of D39 cells in the presence of indicated concentrations of CSP1 and its analogs using the <i>rpsL</i> gene. Transformants were selected on THB agar containing 100 µg/ml streptomycin. Experiments in B and C were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown.</p

Dose dependent inhibition of <i>comX</i> expression and genetic transformation by CSP1 analogs with substitution at glutamate residue in the first position.

<p>(A) CSP1 analogs with substitution at the first glutamate acid competitively inhibit CSP1-mediated induction of <i>comX</i>. D39pcomX::lacZ cells were exposed to 100 ng/ml of CSP1 alone or simultaneously with increasing concentrations of CSP1 analogs. The activity of the <i>comX</i> gene promoter was measured by β-galactosidase activity. Experiments were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown. (B) CSP1 analogs with substitution at the first glutamate acid competitively inhibit the ability of CSP1 to induce genetic transformation. Genetic transformation was performed using the <i>rpsL</i> gene. Transformants were selected on THB agar containing 100 µg/ml streptomycin. Experiments were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown.</p

CSP1-E1A is uniquely able to inhibit the expression of <i>comX</i> and genetic transformation.

<p>(A) CSP-E1A competitively inhibits CSP1-mediated induction of <i>comX</i> in a dose dependent manner. D39pcomX::lacZ cells were exposed to 100 ng/ml of CSP1 alone or simultaneously with increasing concentrations of each CSP1 analog. The activity of the <i>comX</i> gene promoter was measured by β-galactosidase activity. (B) CSP-E1A competitively inhibits CSP1-mediated genetic transformation. Genetic transformation was performed using 30 µg/ml of the D39 genomic DNA containing the <i>rpsL</i> gene. Transformants were selected on THB agar containing 100 µg/ml streptomycin. Experiments were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown.</p

Competitive inhibition of CSP1 by low concentrations of analogs with substitutions of glutamate residue in the first position.

<p>(A) Induction of genetic transformation by each analog using the genomic DNA containing the <i>rpsL</i> gene. Transformants were selected on THB agar containing 100 µg/ml streptomycin. Experiments were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown. (B) Competitive inhibition of genetic transformation by low concentrations of CSP1 analogs. Genetic transformation was performed using the genomic DNA containing the <i>rpsL</i> gene. Transformants were selected on THB agar containing 100 µg/ml streptomycin. Experiments were performed in triplicates and repeated three times. The means ± SD of one typical experiment are shown.</p