OH yields from the CH3CO+O-2 reaction using an internal standard

Laser flash photolysis of CH3C(O)OH at 248 nm was used to create equal zero time yields of CH3CO and OH. The absolute OH yield from the CH3CO + O2 (+M) reaction was determined by following the OH temporal profile using the zero time OH concentration as an internal standard. The OH yield from CH3CO + O2 (+M) was observed to decrease with increasing pressure with an extrapolated zero pressure yield close to unity (1.1 ± 0.2, quoted uncertainties correspond to 95% confidence limits). The results are in quantitative agreement with those obtained from 248 nm acetone photolysis in the presence of O2

Hepatitis C cross-genotype immunity and implications for vaccine development.

While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological responses. Smaller studies on humans and chimpanzees reported seemingly opposing results regarding cross-neutralizing antibodies. We report a lack of cross-genotype immunity in the largest cohort of people to date. In the adjusted Cox proportional hazards model, reinfection with a heterologous HCV genotype (adjusted Hazard Ratio [aHR]: 0.45, 95% CI: 0.25-0.84) was associated with a 55% lower likelihood of re-clearance. Among those who cleared their first infection spontaneously, the likelihood of re-clearance was 49% lower (aHR: 0.51, 95% CI: 0.27-0.94) when reinfected with a heterologous HCV genotype. These findings indicate that immunity against a particular HCV genotype does not offer expanded immunity to protect against subsequent infections with a different HCV genotype. A prophylactic HCV vaccine boosted with multiple HCV genotype may offer a broader and more effective protection

Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort.

BACKGROUND & AIMS: Direct-acting antiviral therapies (DAA) are an important tool for hepatitis C virus (HCV) elimination. However, reinfection among people who inject drugs (PWID) may hamper elimination targets. Therefore, we estimated HCV reinfection rates among DAA-treated individuals, including PWID. METHODS: We analyzed data from the British Columbia Hepatitis Testers Cohort which included ∼1.7 million individuals screened for HCV in British Columbia, Canada. We followed HCV-infected individuals treated with DAAs who achieved a sustained virologic response (SVR) and had ≥1 subsequent HCV RNA measurement to April 22nd, 2018. Reinfection was defined as a positive RNA measurement after SVR. PWID were identified using a validated algorithm and classified based on recent (<3 years) or former (≥3 years before SVR) use. Crude reinfection rates per 100 person-years (PYs) were calculated. Poisson regression was used to model adjusted incidence rate ratios (IRRs) and 95% CIs. RESULTS: Of 4,114 individuals who met the inclusion criteria, most were male (n = 2,692, 65%), born before 1965 (n = 3,411, 83%) and were either recent (n = 875, 21%) or former PWID (n = 1,793, 44%). Opioid-agonist therapy (OAT) was received by 19% of PWID. We identified 40 reinfections during 2,767 PYs. Reinfection rates were higher among recent (3.1/100 PYs; IRR 6.7; 95% CI 1.9-23.5) and former PWID (1.4/100 PYs; IRR 3.7; 95% CI 1.1-12.9) than non-PWID (0.3/100 PYs). Among recent PWID, reinfection rates were higher among individuals born after 1975 (10.2/100 PYs) and those co-infected with HIV (5.7/100 PYs). Only one PWID receiving daily OAT developed reinfection. CONCLUSIONS: Population-level reinfection rates remain elevated after DAA therapy among PWID because of ongoing exposure risk. Engagement of PWID in harm-reduction and support services is needed to prevent reinfections. LAY SUMMARY: Direct-acting antivirals are an effective tool for the treatment of hepatitis C virus, enabling the elimination of the virus. However, some patients who have been successfully treated with direct-acting antivirals are at risk of reinfection. Our findings showed that the risk of reinfection was highest among people with recent injection drug use. Among people who inject drugs, daily use of opioid-agonist therapy was associated with a lower risk of reinfection

Developing an ecologically relevant heterogeneous biofilm model for dental-unit waterlines

This study monitored the biodiversity of microbes cultured from a heterogeneous biofilm which had formed on the lumen of a section of dental waterline tubing over a period of 910 days. By day two bacterial counts on the outlet-water showed that contamination of the system had occurred. After 14 days, a biofilm comparable to that of clinical waterlines, consisting of bacteria, fungi and amoebae had formed. This showed that the proprietary silver coating applied to the lumenal surface of the commercial waterline tubing failed to prevent biofilm formation. Molecular barcoding of isolated culturable microorganisms showed some degree of the diversity of taxa in the biofilm, including the opportunistic pathogen Legionella pneumophila. Whilst the system used for isolation and identification of contaminating microorganisms may underestimate the diversity of organisms in the biofilm, their similarity to those found in the clinical environment makes this a promising test-bed for future biocide testing

Type I restriction enzymes and their relatives

Type I restriction enzymes (REases) are large pentameric proteins with separate restriction (R), methylation (M) and DNA sequence-recognition (S) subunits. They were the first REases to be discovered and purified, but unlike the enormously useful Type II REases, they have yet to find a place in the enzymatic toolbox of molecular biologists. Type I enzymes have been difficult to characterize, but this is changing as genome analysis reveals their genes, and methylome analysis reveals their recognition sequences. Several Type I REases have been studied in detail and what has been learned about them invites greater attention. In this article, we discuss aspects of the biochemistry, biology and regulation of Type I REases, and of the mechanisms that bacteriophages and plasmids have evolved to evade them. Type I REases have a remarkable ability to change sequence specificity by domain shuffling and rearrangements. We summarize the classic experiments and observations that led to this discovery, and we discuss how this ability depends on the modular organizations of the enzymes and of their S subunits. Finally, we describe examples of Type II restriction–modification systems that have features in common with Type I enzymes, with emphasis on the varied Type IIG enzymes

Planning for the Next Global Pandemic

In order to mitigate human and financial losses as a result of future global pandemics, we must plan now. As the Ebola virus pandemic declines, we must reflect on how we have mismanaged this recent international crisis and how we can better prepare for the next global pandemic. Of great concern is the increasing frequency of pandemics occurring over the last few decades. Clearly, the window of opportunity to act is closing. This editorial discusses many issues including priority emerging and re-emerging infectious diseases; the challenges of meeting international health regulations; the strengthening of global health systems; global pandemic funding; and the One Health approach to future pandemic planning. We recommend that the global health community unites to urgently address these issues in order to avoid the next humanitarian crisis

Summary of findings from the evaluation of a pilot medically supervised safer injecting facility

In many cities, infectious disease and overdose epidemics are occurring among illicit injection drug users (IDUs). To reduce these concerns, Vancouver opened a supervised safer injecting facility in September 2003. Within the facility, people inject pre-obtained illicit drugs under the supervision of medical staff. The program was granted a legal exemption by the Canadian government on the condition that a 3-year scientific evaluation of its impacts be conducted. In this review, we summarize the findings from evaluations in those 3 years, including characteristics of IDUs at the facility, public injection drug use and publicly discarded syringes, HIV risk behaviour, use of addiction treatment services and other community resources, and drug-related crime rates. Vancouver's safer injecting facility has been associated with an array of community and public health benefits without evidence of adverse impacts. These findings should be useful to other cities considering supervised injecting facilities and to governments considering regulating their use

Predicting Neisseria gonorrhoeae and Chlamydia trachomatis Infection Using Risk Scores, Physical Examination, Microscopy, and Leukocyte Esterase Urine Dipsticks Among Asymptomatic Women Attending a Family Planning Clinic in Kenya

Background: Sexually transmitted infections (STIs) continue to exert a tremendous health burden on women in developing countries. Poor socioeconomic status, inadequate knowledge, lack of diagnostic facilities, and shortages of effective treatment all contribute to the high incidence of STIs. The use of clinical algorithms for the detection and management of STIs has gained widespread acceptance in settings where there are limited resources. Evaluation of these algorithms have been few, especially in women who are not recognized as members of high-risk groups. Objectives: To develop a simple scoring system based on historical and demographic data, physical findings, microscopy, and leukocyte esterase (LE) urine dipsticks to predict cervical gonococcal and chlamydial infection among asymptomatic women. Methods: One thousand and forty-eight women attending an urban family planning clinic in Nairobi were randomly selected to participate. After the identification of factors that were associated with infection, we assigned one point each for: age 25 or younger, single status, two or more sex partners in the past year, cervical discharge, cervical swab leukocytes, and a positive LE urine dipstick. Identification of any one of these six factors gave a sensitivity of 85% and a specificity of 30% for the detection of cervical infections. A positive LE urine dipstick had a sensitivity of 63 % and a specificity of 47% when used alone and did not contribute to the identification of infection if a physical examination was performed. The application of existing clinical algorithms to this population performed poorly. Conclusions: The use of risk scores, physical examination, microscopy, and the urine LE dipstick, used alone or in combination, as predictors of gonococcal or chlamydial cervical infection was of limited utility in low-risk, asymptomatic women. Accurate diagnostic testing is necessary to optimize treatment