Enhanced Pseudomonas aeruginosa biofilm development mediated by human neutrophils

Cystic fibrosis (CF) lung disease features persistent neutrophil accumulation to the airways from the time of infancy. CF children are frequently exposed to Pseudomonas aeruginosa, and by adulthood, 80% of CF patients are chronically infected. The formation of biofilms is a particularly important phenotypic characteristic of P. aeruginosa that allows for bacterial survival despite aggressive antibiotic therapy and an exuberant immune response. Here, we show that the presence of neutrophils enhances initial P. aeruginosa biofilm development over a period of 72 h through the formation of polymers comprised of actin and DNA. F-actin was found to be a site of attachment for P. aeruginosa. These actin and DNA polymers are present in CF sputum, and disruption of the polymers dispersed the associated P. aeruginosa cells and reduced biofilm development. These findings demonstrate a potential maladaptation of the primary innate response. When the host fails to eradicate the infection, cellular components from necrotic neutrophils can serve as a biological matrix to facilitate P. aeruginosa biofilm formation.     

Passive immunization of neonatal mice against Pneumocystis carinii f. sp. muris enhances control of infection without stimulating inflammation

Pneumocystis carinii is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to infection with Pneumocystis. We have previously shown that there is a significant delay in clearance of the organisms from the lungs of neonatal mice compared to adults. Since alveolar macrophages are the effector cells responsible for killing and clearance of Pneumocystis, we have examined alveolar macrophage activity in neonatal mice. We found that alveolar macrophage activation is delayed about 1 week in Pneumocystis-infected neonates compared to adults. Opsonization of the organism by Pneumocystis-specific antibody resulted in increased clearance of the organism in neonatal mice; however, there was decreased expression of activation markers on neonatal alveolar macrophages and reduced levels of cytokines associated with macrophage activation. Mice born to immunized dams had significant amounts of Pneumocystis-specific immunoglobulin G in their lungs and serum at day 7 postinfection, whereas mice born to naive dams had merely detectable levels. This difference correlated with enhanced Pneumocystis clearance in mice born to immunized dams. The increase in specific antibody, however, did not result in significant inflammation in the lungs, as no differences in numbers of activated CD4+ cells were observed. Furthermore, there was no difference in cytokine or chemokine concentrations in the lungs of pups born to immune compared to naive dams. These findings indicate that specific antibody plays an important role in Pneumocystis clearance from lungs of infected neonates; moreover, this process occurs without inducing inflammation in the lungs.     

Young people's sexual health in South Africa: HIV prevalence and sexual behaviors from a nationally representative household survey

OBJECTIVES: To determine the prevalence of HIV infection, HIV risk factors, and exposure to national HIV prevention programs, and to identify factors associated with HIV infection among South African youth, aged 15-24 years. DESIGN: A cross-sectional, nationally representative, household survey. METHODS: From March to August 2003 we conducted a national survey of HIV prevalence and sexual behavior among 11 904 15-24 year olds. Multivariable models for HIV infection were restricted to sexually experienced youth. RESULTS: Young women were significantly more likely to be infected with HIV in comparison with young men (15.5 versus 4.8%). Among men, a history of genital ulcers in the past 12 months was associated with HIV infection [adjusted odds ratio (AOR), 1.91; 95% confidence interval (CI), 1.04-3.49) whereas among women a history of unusual vaginal discharge in the past 12 months was associated with HIV infection (AOR, 1.75; 95% CI, 1.26-2.44). Young women with older partners were also at increased risk of HIV infection. Among both men and women, increasing partner numbers and inconsistent condom use were significantly associated with HIV infection. Males and females who reported participation in at least one loveLife program were less likely to be infected with HIV (AOR, 0.60; 95% CI, 0.40-0.89; AOR, 0.61; 95% CI, 0.43-0.85, respectively). CONCLUSION: This survey confirms the high HIV prevalence among young people in South Africa and, in particular, young women's disproportionate risk. Programs for youth must continue to promote partner reduction, consistent condom use and prompt treatment for sexually transmitted infections while also addressing contextual factors that make it difficult for them to implement behavior change.     

A community-based study to examine the effect of a youth HIV prevention intervention on young people aged 15-24 in South Africa: results of the baseline survey

OBJECTIVES: To determine whether South African youths living in communities that had either of two youth human immunodeficiency virus (HIV) prevention interventions [(a) loveLife Youth Centre or (b) loveLife National Adolescent Friendly Clinic Initiative] would have a lower prevalence of HIV, sexually transmitted infections (STIs), and high risk sexual behaviours than communities without either of these interventions. METHODS: In 2002 the baseline survey of a quasi-experimental, community-based study was conducted in South Africa. In total 33 communities were included in three study arms (11 communities per study arm). The final sample included 8735 youths aged 15-24 years. All participants took part in a behavioural interview and were tested for HIV, gonorrhoea (Neisseria gonorrhoeae) and Chlamydia (Chlamydia trachomatis). RESULTS: HIV prevalence was 20.0% among females and 7.5% among males (OR 3.93 95% CI 2.51-6.15). There were no significant differences between study arms for HIV, NG or CT prevalence at baseline. In multiple regression analyses, HIV was significantly associated with NG infection (OR 1.96 95% CI 1.24-3.12) but not with CT infection. Youths who reported >1 lifetime partner were also significantly more likely to be infected with HIV (OR 1.98 95% CI 1.55-2.52), as were those who reported ever having engaged in transactional sex (OR 1.86 P = 0.02) or having had genital ulcers in the past 12 months (OR 1.71 P < or = 0.001). CONCLUSIONS: HIV prevention programmes must ensure that gender inequities that place young women at greater risk for HIV infection are urgently addressed and they must continue to emphasize the importance of reducing the number of sexual partners and STI treatment.     

Outcomes in splenic marginal zone lymphoma: analysis of 107 patients treated in British Columbia

Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non‐Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30–88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10‐year overall survival for first‐line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26–0·88, P = 0·017]. The 10‐year failure‐free survival (FFS) after first‐line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28–0·80, P = 0·004). Among the 38 patients who received first‐line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31–1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10‐year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL.     

Novel Method for Processing Respiratory Specimens for Detection of Mycobacteria by Using C18-Carboxypropylbetaine: Blinded Study

A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced. This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no. 78195-27-4), also known as C₁₈-carboxypropylbetaine (CB-18). In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory specimens were tested. Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics—Baltimore. A total of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters. Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18. The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing. There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens. The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity. This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.     

Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44 +/- 10 years of age) scheduled for a medically indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. Of the TAG accounted for in liver, 59.0% +/- 9.9% of TAG arose from NEFAs; 26.1% +/- 6.7%, from DNL; and 14.9% +/- 7.0%, from the diet. The pattern of labeling in VLDL was similar to that in liver, and throughout the 4 days of labeling, the liver demonstrated reciprocal use of adipose and dietary fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal variation. These quantitative metabolic data document that both elevated peripheral fatty acids and DNL contribute to the accumulation of hepatic and lipoprotein fat in NAFLD.     

Impact of ancestry and body size on sonographic ulnar nerve dimensions

IntroductionThe purpose of this study was to investigate the impact that geographic ancestry and body size have on ultrasonographic measurements of the ulnar nerve size measured at the elbow.Materials and methodsWe performed anthropometric measurements of body size and ultrasonographic measurements of the ulnar nerve at the elbow on 13 Vietnamese and 24 European participants. Regression analysis was used to determine the effect of body size and geographic ancestry on ulnar nerve size.ResultsBMI had the greatest impact on ulnar nerve size. The short axis diameter was least resilient, and the long axis diameter was the most resilient to the effects of body size and geographic ancestry.DiscussionThe long axis diameter has an apparent immunity to the influences of overall body size, arm size, or geographic ancestry and has the most potential as a sensitive discriminator between normal nerves and nerves affected by ulnar neuropathy at the elbow.