Apoptotic cell clearance in chronic inflammation of lateral neck cysts

The mechanism driving accumulation of large numbers of apoptotic and necrotic neutrophils in inflamed lateral neck cysts (LNC), in the absence of infection, remains obscure. The cellular content of cysts obtained from 17 patients was co-cultured with human macrophages. Phagocytosis levels of cyst-derived neutrophils were determined and compared to the uptake of spontaneously apoptotic neutrophils. Simultaneously, the expression of cytokines in macrophages exposed to cyst contents was measured. In comparison to spontaneously apoptotic neutrophils, the phagocytosis of LNC-derived neutrophils by macrophages was inefficient. An inverse correlation between neutrophil content in LNC and their uptake was observed. Macrophages co-cultured with cyst contents responded with variable expression of IL-6, TNF-α and IL-10. The hindered clearance of apoptotic neutrophils in LNC may lead to secondary necrosis of these cells and stimulation of the inflammatory reaction. Together with local production of anti-inflammatory cytokines, this may fuel chronic inflammation in the cysts

Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists

is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens. genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa. was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation

Exercise-induced laryngeal obstruction: natural history and effect of surgical treatment

The current follow-up study concerning the supraglottic type of exercise-induced laryngeal obstruction (EILO) was performed to reveal the natural history of supraglottic EILO and compare the symptoms, as well as the laryngeal function in conservatively versus surgically treated patients. A questionnaire-based survey was conducted 2–5 years after EILO was diagnosed by a continuous laryngoscopy exercise (CLE) test in 94 patients with a predominantly supraglottic obstruction. Seventy-one patients had been treated conservatively and 23 with laser supraglottoplasty. The questionnaire response rate was 70 and 100% in conservatively treated (CT) and surgically treated (ST) patients, respectively. A second CLE test was performed in 14 CT and 19 ST patients. A visual analogue scale on symptom severity indicated improvements in both the groups, i.e. mean values (± standard deviations) declined from 73 (20) to 53 (26) (P < 0.001) in the CT group and from 87 (26) to 25 (27) (P < 0.001) in the ST group. At follow-up, ST patients reported lower scores regarding current level of complaints, and higher ability to perform exercise, as well as to push themselves physically, all compared to CT patients (P < 0.001). CLE scores were normalized in 3 of 14 (21%) CT and 16 of 19 (84%) ST patients (Z = −3.6; P < 0.001). In conclusion, symptoms of EILO diagnosed in adolescents generally decreased during 2–5 years follow-up period but even more after the surgical treatment. Patients with supraglottic EILO may benefit from supraglottoplasty both as to laryngeal function and symptom relief

Adherence to recommendations by infectious disease consultants and its influence on outcomes of intravenous antibiotic-treated hospitalized patients

BACKGROUND: Consultation to infectious diseases specialists (ID), although not always performed by treating physicians, is part of hospital's daily practice. This study analyses adherence by treating physicians to written ID recommendations (inserted in clinical records) and its effect on outcome in hospitalized antibiotic-treated patients in a tertiary hospital in Spain. METHODS: A prospective, randomized, one-year study was performed. Patients receiving intravenous antimicrobial therapy prescribed by treating physicians for 3 days were identified and randomised to intervention (insertion of written ID recommendations in clinical records) or non-intervention. Appropriateness of empirical treatments (by treating physicians) was classified as adequate, inadequate or unnecessary. In the intervention group, adherence to recommendations was classified as complete, partial or non-adherence. RESULTS: A total of 1173 patients were included, 602 in the non-intervention and 571 in the intervention group [199 (34.9%) showing complete adherence, 141 (24.7%) partial adherence and 231 (40.5%) non-adherence to recommendations]. In the multivariate analysis for adherence (R2 Cox=0.065, p=0.009), non-adherence was associated with prolonged antibiotic prophylaxis (p=0.004; OR=0.37, 95%CI=0.19-0.72). In the multivariate analysis for clinical failure (R2 Cox=0.126, p<0.001), Charlson index (p<0.001; OR=1.19, 95%CI=1.10-1.28), malnutrition (p=0.006; OR=2.00, 95%CI=1.22-3.26), nosocomial infection (p<0.001; OR=4.12, 95%CI=2.27-7.48) and length of hospitalization (p<0.001; OR=1.01, 95%CI=1.01-1.02) were positively associated with failure, while complete adherence (p=0.001; OR=0.35, 95%CI=0.19-0.64) and adequate initial treatment (p=0.010; OR=0.39, 95%CI=0.19-0.80) were negatively associated. CONCLUSIONS: Adherence to ID recommendations by treating physicians was associated with favorable outcome, in turn associated with shortened length of hospitalization. This may have important health-economic benefits and stimulates further investigation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83234896. http://www.controlled-trials.com/isrctn/sample_documentation.asp

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Histoplasma capsulatum proteome response to decreased iron availability

<p>Abstract</p> <p>Background</p> <p>A fundamental pathogenic feature of the fungus <it>Histoplasma capsulatum </it>is its ability to evade innate and adaptive immune defenses. Once ingested by macrophages the organism is faced with several hostile environmental conditions including iron limitation. <it>H. capsulatum </it>can establish a persistent state within the macrophage. A gap in knowledge exists because the identities and number of proteins regulated by the organism under host conditions has yet to be defined. Lack of such knowledge is an important problem because until these proteins are identified it is unlikely that they can be targeted as new and innovative treatment for histoplasmosis.</p> <p>Results</p> <p>To investigate the proteomic response by <it>H. capsulatum </it>to decreasing iron availability we have created <it>H. capsulatum </it>protein/genomic databases compatible with current mass spectrometric (MS) search engines. Databases were assembled from the <it>H. capsulatum </it>G217B strain genome using gene prediction programs and expressed sequence tag (EST) libraries. Searching these databases with MS data generated from two dimensional (2D) in-gel digestions of proteins resulted in over 50% more proteins identified compared to searching the publicly available fungal databases alone. Using 2D gel electrophoresis combined with statistical analysis we discovered 42 <it>H. capsulatum </it>proteins whose abundance was significantly modulated when iron concentrations were lowered. Altered proteins were identified by mass spectrometry and database searching to be involved in glycolysis, the tricarboxylic acid cycle, lysine metabolism, protein synthesis, and one protein sequence whose function was unknown.</p> <p>Conclusion</p> <p>We have created a bioinformatics platform for <it>H. capsulatum </it>and demonstrated the utility of a proteomic approach by identifying a shift in metabolism the organism utilizes to cope with the hostile conditions provided by the host. We have shown that enzyme transcripts regulated by other fungal pathogens in response to lowering iron availability are also regulated in <it>H. capsulatum </it>at the protein level. We also identified <it>H. capsulatum </it>proteins sensitive to iron level reductions which have yet to be connected to iron availability in other pathogens. These data also indicate the complexity of the response by <it>H. capsulatum </it>to nutritional deprivation. Finally, we demonstrate the importance of a strain specific gene/protein database for <it>H. capsulatum </it>proteomic analysis.</p

Does administration of non-steroidal anti-inflammatory drug determine morphological changes in adrenal cortex: ultrastructural studies

Rofecoxib (Vioxx© made by Merck Sharp & Dohme, the USA) is a non-steroidal anti-inflammatory drug which belongs to the group of selective inhibitors of cyclooxygenasis-2, i.e., coxibs. Rofecoxib was first registered in the USA, in May 1999. Since then the drug was received by millions of patients. Drugs of this group were expected to exhibit increased therapeutic action. Additionally, there were expectations concerning possibilities of their application, at least as auxiliary drugs, in neoplastic therpy due to intensifying of apoptosis. In connection with the withdrawal of Vioxx© (rofecoxib) from pharmaceutical market, attempts were made to conduct electron-microscopic evaluation of cortical part of the adrenal gland in preparations obtained from animals under influence of the drug. Every morning animals from the experimental group (15 rats) received rofecoxib (suspension in physiological saline)—non-steroidal anti-inflammatory drug (Vioxx©, Merck Sharp and Dohme, the USA), through an intragastric tube in the dose of 1.25 mg during 8 weeks. In the evaluated material, there was found a greater number of secretory vacuoles and large, containing cholesterol and other lipids as well as generated glucocorticoids, lipid drops in cytoplasm containing prominent endoplasmic reticulum. There were also found cells with cytoplasm of smaller density—especially in apical and basal parts of cells. Mitochondria occasionally demonstrated features of delicate swelling. The observed changes, which occurred on cellular level with application of large doses of the drug, result from mobilization of adaptation mechanisms of the organism

Uncertainty Compensation in Human Attention: Evidence from Response Times and Fixation Durations

BACKGROUND: Uncertainty and predictability have remained at the center of the study of human attention. Yet, studies have only examined whether response times (RT) or fixations were longer or shorter under levels of stimulus uncertainty. To date, no study has examined patterns of stimuli and responses through a unifying framework of uncertainty. METHODOLOGY/PRINCIPAL FINDINGS: We asked 29 college students to generate repeated responses to a continuous series of visual stimuli presented on a computer monitor. Subjects produced these responses by pressing on a keypad as soon a target was detected (regardless of position) while the durations of their visual fixations were recorded. We manipulated the level of stimulus uncertainty in space and time by changing the number of potential stimulus locations and time intervals between stimulus presentations. To allow the analyses to be conducted using uncertainty as common description of stimulus and response we calculated the entropy of the RT and fixation durations. We tested the hypothesis of uncertainty compensation across space and time by fitting the RT and fixation duration entropy values to a quadratic surface. The quadratic surface accounted for 80% of the variance in the entropy values of both RT and fixation durations. RT entropy increased as a function of spatial and temporal uncertainty of the stimulus, alongside a symmetric, compensatory decrease in the entropy of fixation durations as the level of spatial and temporal uncertainty of the stimuli was increased. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that greater uncertainty in the stimulus leads to greater uncertainty in the response, and that the effects of spatial and temporal uncertainties are compensatory. We also observed compensatory relationship across the entropies of fixation duration and RT, suggesting that a more predictable visual search strategy leads to more uncertain response patterns and vice versa

Introduction to “Binary Binds”: Deconstructing Sex and Gender Dichotomies in Archaeological Practice

YesGender archaeology has made significant strides toward deconstructing the hegemony of binary categorizations. Challenging dichotomies such as man/woman, sex/gender, and biology/culture, approaches informed by poststructuralist, feminist, and queer theories have moved beyond essentialist and universalist identity constructs to more nuanced configurations. Despite the theoretical emphasis on context, multiplicity, and fluidity, binary starting points continue to streamline the spectrum of variability that is recognized, often reproducing normative assumptions in the evidence. The contributors to this special issue confront how sex, gender, and sexuality categories condition analytical visibility, aiming to develop approaches that respond to the complexity of theory in archaeological practice. The papers push the ontological and epistemological boundaries of bodies, personhood, and archaeological possibility, challenging a priori assumptions that contain how sex, gender, and sexuality categories are constituted and related to each other. Foregrounding intersectional approaches that engage with ambiguity, variability, and difference, this special issue seeks to “de-contain” categories, assumptions, and practices from “binding” our analytical gaze toward only certain kinds of persons and knowledges, in interpretations of the past and practices in the present