Chlamydial infection among patients attending STD and genitourinary clinics in Taiwan

<p>Abstract</p> <p>Background</p> <p>The main objective of this study is to examine the epidemiology of <it>Chlamydia trachomatis </it>(CT) infection amongst patients (473 men, 180 women) seen two hospitals in Taiwan.</p> <p>Methods</p> <p>Between July 2004 and June 2005, a total of 653 patients provided first-void urine samples for examination of CT using PCR assay.</p> <p>Results</p> <p>The overall prevalence of CT infection was 18.4% (95% confidence interval [CI] 17.3–19.5). Prevalence for men and women were 16.7 % (95% CI 15.3–18.0%) and 22.8% (95% CI 17.5–28.1%), respectively. Age group-specific prevalence was 25.7% (95% CI 22.5–28.9%) in < 20 year olds, 23.5% (95% CI 20.3–26.7%) in 20–24 year olds, 22.3% (95% CI 18.9–25.7%) in 25–30 year olds, and 11.5% (95% CI 10.3–12.7%) in > 30 year olds. Independent risk factors for chlamydial infection included younger age (aged ≤ 30 years) (adjusted odds ratio [AOR] = 2.44; 95% CI 1.52–3.84; <it>p </it>< 0.001), inconsistent condom use (AOR = 2.01; 95% CI 1.32–3.06; <it>p </it>< 0.001), being symptomatic (dysuria, urethral discharge) at the time of testing (AOR = 1.84; 95% CI 1.21–2.80; <it>p </it>< 0.001), and having <it>N. gonorrhoeae </it>infection (AOR = 3.82; 95% CI 2.20–6.58; <it>p </it>< 0.001).</p> <p>Conclusion</p> <p>Genital chlamydial infection is an important sexually transmitted disease in Taiwan. Young Taiwanese persons attending a STD clinic should be screened for CT infection and counselled on condom use.</p

Improved outcomes for hepatic trauma in England and Wales over a decade of trauma and hepatobiliary surgery centralisation

Background: Over the last decade trauma services have undergone a reconfiguration in England and Wales. The objective is to describe the epidemiology, management and outcomes for liver trauma over this period and examine factors predicting survival. Methods: Patients sustaining hepatic trauma were identified using the Trauma Audit and Research Network database. Demographics, management and outcomes were assessed between January 2005 and December 2014 and analysed over five, 2-year study periods. Independent predictor variables for the outcome of liver trauma were analysed using multiple logistic regression. Results: 4368 Patients sustained hepatic trauma (with known outcome) between January 2005 and December 2014. Median age was 34 years (interquartile range 23–49). 81% were due to blunt and 19% to penetrating trauma. Road traffic collisions were the main mechanism of injury (58.2%). 241 patients (5.5%) underwent liver-specific surgery. The overall 30-day mortality rate was 16.4%. Improvements were seen in early consultant input, frequency and timing of computed tomography (CT) scanning, use of tranexamic acid and 30-day mortality over the five time periods. Being treated in a unit with an on-site HPB service increased the odds of survival (odds ratio 3.5, 95% confidence intervals 2.7–4.5). Conclusions: Our study has shown that being treated in a unit with an on-site HPB service increased the odds of survival. Further evaluation of the benefits of trauma and HPB surgery centralisation is warranted

Household secondhand smoke exposure of elementary schoolchildren in Southern Taiwan and factors associated with their confidence in avoiding exposure: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Exposure to household Secondhand Smoke (SHS) poses a major health threat to children after an indoor smoking ban was imposed in Taiwan. This study aimed to assess the household SHS exposure in elementary school children in southern Taiwan and the factors associated with their avoidance of SHS exposure before and after the implementation of Taiwan's new Tobacco Hazards Prevention Act in 2009.</p> <p>Methods</p> <p>In this cross-sectional school-based study, data on household SHS exposure, avoidance of SHS and related variables was obtained from the 2008 and 2009 Control of School-aged Children Smoking Study Survey. A random sample of 52 elementary schools was included. A total of 4450 3-6 graders (aged 8-13) completed the questionnaire. Regression models analyzed factors of children's self-confidence to avoid household SHS exposure.</p> <p>Results</p> <p>Over 50% of children were found to have lived with a family member who smoked in front of them after the new law enacted, and 35% of them were exposed to household SHS more than 4 days a week. Having a positive attitude toward smoking (β = -0.05 to -0.06) and high household SHS exposure (β = -0.34 to -0.47) were significantly associated with a lower avoidance of SHS exposure. Comparing to girls, boys had lower scores in their knowledge of tobacco hazards; and this factor was significantly related to their SHS avoidance (β = 0.13-0.14).</p> <p>Conclusions</p> <p>The intervention program should enhance school children do actively avoid exposure to SHS in home settings, and more importantly, provide tobacco hazard knowledge to male students to avoid exposure to household SHS for themselves. The results also provide further evidence that Tobacco Hazards Prevention Act should perhaps be extended to the family environment in order to protect children from the hazards of household SHS exposure.</p

An Efficient Strategy for Broad-Range Detection of Low Abundance Bacteria without DNA Decontamination of PCR Reagents

BACKGROUND: Bacterial DNA contamination in PCR reagents has been a long standing problem that hampers the adoption of broad-range PCR in clinical and applied microbiology, particularly in detection of low abundance bacteria. Although several DNA decontamination protocols have been reported, they all suffer from compromised PCR efficiency or detection limits. To date, no satisfactory solution has been found. METHODOLOGY/PRINCIPAL FINDINGS: We herein describe a method that solves this long standing problem by employing a broad-range primer extension-PCR (PE-PCR) strategy that obviates the need for DNA decontamination. In this method, we first devise a fusion probe having a 3'-end complementary to the template bacterial sequence and a 5'-end non-bacterial tag sequence. We then hybridize the probes to template DNA, carry out primer extension and remove the excess probes using an optimized enzyme mix of Klenow DNA polymerase and exonuclease I. This strategy allows the templates to be distinguished from the PCR reagent contaminants and selectively amplified by PCR. To prove the concept, we spiked the PCR reagents with Staphylococcus aureus genomic DNA and applied PE-PCR to amplify template bacterial DNA. The spiking DNA neither interfered with template DNA amplification nor caused false positive of the reaction. Broad-range PE-PCR amplification of the 16S rRNA gene was also validated and minute quantities of template DNA (10-100 fg) were detectable without false positives. When adapting to real-time and high-resolution melting (HRM) analytical platforms, the unique melting profiles for the PE-PCR product can be used as the molecular fingerprints to further identify individual bacterial species. CONCLUSIONS/SIGNIFICANCE: Broad-range PE-PCR is simple, efficient, and completely obviates the need to decontaminate PCR reagents. When coupling with real-time and HRM analyses, it offers a new avenue for bacterial species identification with a limited source of bacterial DNA, making it suitable for use in clinical and applied microbiology laboratories

Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer mouse models

Small interfering RNA (siRNA) shows great promise in cancer therapy, but its effectiveness in vivo still remains a crucial issue for its transition into the clinics. Although the successful use of polyethylene glycol (PEG)ylated lipidic delivery systems have already been reported, most of the formulation procedures used are labour intensive and also result in unstable end products. We have previously developed a simple yet efficient hydration-of-freeze-dried- matrix (HFDM) method to entrap siRNA within lipid particles, in which the products exhibited superior stability. Here, we show that these HFDM-formulated particles are stable in the presence of serum and can deliver siRNA efficiently to tumours after intravenous administration. Using these particles, around 50% knockdown of the target gene expression was observed in tumours. With the use of siRNA targeting the E6/7 oncogenes expressed in cervical cancer, we showed a 50% reduction in tumour size. This level of tumour growth suppression was comparable to that achieved from cisplatin at the clinically used dose. Overall, our results demonstrate the feasibility of using HFDM-formulated particles to systematically administer E6/7-targeted siRNA for cervical cancer treatment. The simplicity of preparation procedure along with superior product stability obtained from our method offers an innovative approach for the in vivo delivery of siRNA

Snake Cytotoxins Bind to Membranes via Interactions with Phosphatidylserine Head Groups of Lipids

The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells

Nε−Lysine Acetylation of a Bacterial Transcription Factor Inhibits Its DNA-Binding Activity

Evidence suggesting that eukaryotes and archaea use reversible Nε-lysine (Nε-Lys) acetylation to modulate gene expression has been reported, but evidence for bacterial use of Nε-Lys acetylation for this purpose is lacking. Here, we report data in support of the notion that bacteria can control gene expression by modulating the acetylation state of transcription factors (TFs). We screened the E. coli proteome for substrates of the bacterial Gcn5-like protein acetyltransferase (Pat). Pat acetylated four TFs, including the RcsB global regulatory protein, which controls cell division, and capsule and flagellum biosynthesis in many bacteria. Pat acetylated residue Lys180 of RcsB, and the NAD+-dependent Sir2 (sirtuin)-like protein deacetylase (CobB) deacetylated acetylated RcsB (RcsBAc), demonstrating that Nε-Lys acetylation of RcsB is reversible. Analysis of RcsBAc and variant RcsB proteins carrying substitutions at Lys180 provided biochemical and physiological evidence implicating Lys180 as a critical residue for RcsB DNA-binding activity. These findings further the likelihood that reversible Nε-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells

Modulation of Aβ(42 )low-n oligomerization using a novel yeast reporter system

BACKGROUND: While traditional models of Alzheimer's disease focused on large fibrillar deposits of the Aβ(42 )amyloid peptide in the brain, recent work suggests that the major pathogenic effects may be attributed to SDS-stable oligomers of Aβ(42). These Aβ(42 )oligomers represent a rational target for therapeutic intervention, yet factors governing their assembly are poorly understood. RESULTS: We describe a new yeast model system focused on the initial stages of Aβ(42 )oligomerization. We show that the activity of a fusion of Aβ(42 )to a reporter protein is compromised in yeast by the formation of SDS-stable low-n oligomers. These oligomers are reminiscent of the low-n oligomers formed by the Aβ(42 )peptide in vitro, in mammalian cell culture, and in the human brain. Point mutations previously shown to inhibit Aβ(42 )aggregation in vitro, were made in the Aβ(42 )portion of the fusion protein. These mutations both inhibited oligomerization and restored activity to the fusion protein. Using this model system, we found that oligomerization of the fusion protein is stimulated by millimolar concentrations of the yeast prion curing agent guanidine. Surprisingly, deletion of the chaperone Hsp104 (a known target for guanidine) inhibited oligomerization of the fusion protein. Furthermore, we demonstrate that Hsp104 interacts with the Aβ(42)-fusion protein and appears to protect it from disaggregation and degradation. CONCLUSION: Previous models of Alzheimer's disease focused on unravelling compounds that inhibit fibrillization of Aβ(42), i.e. the last step of Aβ(42 )assembly. However, inhibition of fibrillization may lead to the accumulation of toxic oligomers of Aβ(42). The model described here can be used to search for and test proteinacious or chemical compounds for their ability to interfere with the initial steps of Aβ(42 )oligomerization. Our findings suggest that yeast contain guanidine-sensitive factor(s) that reduce the amount of low-n oligomers of Aβ(42). As many yeast proteins have human homologs, identification of these factors may help to uncover homologous proteins that affect Aβ(42 )oligomerization in mammals

Low Clinical Burden of 2009 Pandemic Influenza A (H1N1) Infection during Pregnancy on the Island of La Réunion

BACKGROUND: Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic (pdm). The purpose of this prospective register-based cohort-study was to characterize the clinical virulence of the pdm (H1N1/09)v during pregnancy in La Réunion. METHODS/PRINCIPAL FINDINGS: Over a twelve-week pdm wave (13 July to 3 October 2009), 294 pregnant women presented with an influenza-like illness (ILI) to one of the three maternity departments of the South Reunion area, Indian Ocean. Out of these, 278 were checked by RT-PCR for influenza viruses (157 positive and 121 negative, of whom, 141 with pdm flu and 132 with ILIs of non pdm origin, 5 untyped). The median body temperature was higher in women experiencing pdm flu than in those with non pdm ILI (38.9 degrees C versus 38.3 degrees C, P<0.0001), without evidence linked to circulating viremia. Oseltamivir was given for 86% of pdm flu cases in a median time inferior than 48 hrs (range 0-7 days). The hospitalization rate for pdm flu was of 60% and not associated with underlying conditions. Six viral pneumonia and fourteen asthma attacks were observed among 84 hospitalized pdm flu cases, of whom, only one led to the ICU for an acute lung injury. No maternal death occurred during the pdm wave. None adverse pregnancy outcome was associated with pdm flu. No congenital birth defect, nor early-onset neonatal influenza infection was attributable to pdm flu exposure. CONCLUSIONS/SIGNIFICANCE: This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy. The reasons for which the clinical burden of H1N1/09 influenza virus may differ worldwide raise questions about a differential local viral-strain effect and public health preparedness, notably in timely access to special care and antiviral treatments