Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone

Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

The pattern of penetration and aspiration in acute stroke survivors

Background and Aims: Aspiration is common in acute stroke survivors with dysphagia, is associated with increased pneumonia rates, and is an independent predictor of mortality. However, studies evaluating the nature and pattern of penetration and aspiration post-stroke are lacking. Method: The Penetration-Aspiration Scale (PAS) was used to rate baseline videofluoroscopic swallowing studies of 17 dysphagic stroke survivors from the STEPS trial of pharyngeal electrical stimulation (onset <14 days, mean 74 years). Analysis was performed on 6 x 5ml boli and 1 x 50ml bolus (thin fluids with contrast agent at 40% wt/vol), recorded at 25 f/s. Every swallow to clear each 5ml or 50ml bolus was counted, given a PAS score and labelled a primary or secondary (clearing) swallow. Results: In total, 285 swallows were viewed. Due to poor image quality, 7% of swallows were excluded. At a bolus level, for 5ml/50ml swallows, results showed 68%/42% normal swallows, 14%/27% penetration and 18%/31% aspiration respectively. At a subject level, 5ml: only 3 patients scored within normal limits for all boli; 50ml: no subject swallowed without showing penetration or aspiration at some point. Higher penetration and aspiration scores occurred on 50ml. Aspirated material was rarely fully cleared, even in those subjects who demonstrated a cough response (5ml: 2%, 50 ml: 0%). Conclusion: Aspiration in post-stroke dysphagia appears to fluctuate in presentation within and between boli. Bedside assessments should take into account variability and sample enough swallows. In addition, clinicians should not assume coughing clears aspirated material. Quality of image capture must be optimised for future studies

Pediatric Transplantation in the United States, 1997–2006

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73373/1/j.1600-6143.2008.02172.x.pd

ISWE: A Case Study of Technology Utilization

The International Space Welding Experiment is a joint project between the E.O. Paton Welding Institute of Kiev, Ukraine and the George C. Marshall Space Flight Center in Huntsville, Alabama. When an international partner is involved in a project, differences in design and testing philosophy can become a factor in the development of the hardware. This report addresses selected issues that arose during the ISWE hardware development as well as the solutions the ISWE team made

Anisotropy in high-frequency broadband acoustic backscattering in the presence of turbulent microstructure and zooplankton

Author Posting. © Acoustical Society of America, 2012. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 132 (2012): 670-679, doi:10.1121/1.4730904.High-frequency broadband (120–600 kHz) acoustic backscattering measurements have been made in the vicinity of energetic internal waves. The transducers on the backscattering system could be adjusted so as to insonify the water-column either vertically or horizontally. The broadband capabilities of the system allowed spectral classification of the backscattering. The distribution of spectral shapes is significantly different for scattering measurements made with the transducers oriented horizontally versus vertically, indicating that scattering anisotropy is present. However, the scattering anisotropy could not be unequivocally explained by either turbulent microstructure or zooplankton, the two primary sources of scattering expected in internal waves. Daytime net samples indicate a predominance of short-aspect-ratio zooplankton. Using zooplankton acoustic scattering models, a preferential orientation of the observed zooplankton cannot explain the measured anisotropy. Yet model predictions of scattering from anisotropic turbulent microstructure, with inputs from coincident microstructure measurements, were not consistent with the observations. Possible explanations include bandwidth limitations that result in many spectra that cannot be unambiguously attributed to turbulence or zooplankton based on spectral shape. Extending the acoustic bandwidth to cover the range from 50 kHz to 2 MHz could help improve identification of the dominant sources of backscattering anisotropy

Risk of reproductive complications following chlamydia testing:a population-based retrospective cohort study in Denmark

SummaryBackgroundUncertainty in the risk of reproductive complications (pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility) following chlamydia infection and repeat infection hampers the design of evidence-based chlamydia control programmes. We estimate the association between diagnosed chlamydia and episodes of hospital health care (inpatient, outpatient, and emergency department) for a reproductive complication.MethodsWe constructed and analysed a retrospective population-based cohort of women aged 15–44 years from administrative records in Denmark (1995–2012). We used a subset of the national Danish Chlamydia Study. The master dataset contains all residents of Denmark (including Greenland) who had a positive chlamydia test recorded by a public health microbiology laboratory from Jan 1, 1992, to Nov 2, 2011. Individuals were randomly matched (by age and sex) to four individuals drawn from the population register (Danish Civil Registration System) who did not have a positive chlamydia test during this interval. The outcomes in the study were hospital episodes of health-care (inpatient, outpatient, and emergency department) with a diagnosis of pelvic inflammatory disease, ectopic pregnancy, or tubal factor infertility.FindingsThe 516 720 women (103 344 positive, 182 879 negative, 230 497 never-tested) had a mean follow-up of 7·96 years. Compared with women with only negative tests, the risk of each complication was 30% higher in women with one or more positive tests (pelvic inflammatory disease, adjusted hazard ratio [AHR] 1·50 [95% CI 1·43–1·57]; ectopic pregnancy, AHR 1·31 [1·25–1·38]; tubal factor infertility, AHR 1·37 [1·24–1·52]) and 60% lower in women who were never-tested (pelvic inflammatory disease, AHR 0·33 [0·31–0·35]; ectopic pregnancy, AHR 0·42 [0·39–0·44]; tubal factor infertility AHR 0·29 [0·25–0·33]). A positive test had a minor absolute impact on health as the difference in the lifetime incidence of complications was small between women who tested positive and those who tested negative (pelvic inflammatory disease, 0·6%; ectopic pregnancy, 0·2%; tubal factor infertility, 0·1%). Repeat infections increased the risk of pelvic inflammatory disease by a further 20% (AHR 1·20, 95% CI 1·11–1·31).InterpretationA single diagnosed chlamydia infection increased the risk of all complications and a repeat diagnosed infection further increased the risk of pelvic inflammatory disease. Therefore, control programmes must prevent first and repeat infections to improve women's reproductive health.FundingUnrestricted partial funding from Frederiksberg Kommune, Frederiksberg, Denmark. BD held an Medical Research Council Population Health Scientist Fellowship (G0902120). KT held an National Institute for Health Research Post-Doctoral Fellowship 2009-02-055