Epidemiology and Microbiologic Characterization of Nosocomial Candidemia from a Brazilian National Surveillance Program

Candidemia is a growing problem in hospitals all over the world. Despite advances in the medical support of critically ill patients, candidiasis leads to prolonged hospitalization, and has a crude mortality rate around 50%. We conducted a multicenter surveillance study in 16 hospitals distributed across five regions of Brazil to assess the incidence, species distribution, antifungal susceptibility, and risk factors for bloodstream infections due to Candida species. From June 2007 to March 2010, we studied a total of 2,563 nosocomial bloodstream infection (nBSI) episodes. Candida spp. was the 7^th most prevalent agent. Most of the patients were male, with a median age of 56 years. A total of 64 patients (46.7%) were in the ICU when candidemia occurred. Malignancies were the most common underlying condition (32%). The crude mortality rate of candidemia during the hospital admission was 72.2%. Non-albicans species of Candida accounted for 65.7% of the 137 yeast isolates. C. albicans (34.3%), Candida parapsilosis (24.1%), Candida tropicalis (15.3%) and Candida glabrata (10.2%) were the most prevalent species. Only 47 out of 137 Candida isolates were sent to the reference laboratory for antifungal susceptibility testing. All C. albicans, C. tropicalis and C. parapsilosis isolates were susceptible to the 5 antifungal drugs tested. Among 11 C. glabrata isolates, 36% were resistant to fluconazole, and 64% SDD. All of them were susceptible to anidulafungin and amphotericin B. We observed that C. glabrata is emerging as a major player among non-albicans Candida spp. and fluconazole resistance was primarily confined to C. glabrata and C. krusei strains. Candida resistance to echinocandins and amphotericin B remains rare in Brazil.Mortality rates remain increasingly higher than that observed in the Northern Hemisphere countries, emphasizing the need for improving local practices of clinical management of candidemia, including early diagnosis, source control and precise antifungal therapy.     

DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis

Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for various inflammatory conditions as well as for cancer. Despite its widespread use, there is a paucity of data regarding its safety and efficacy as well as its mechanism of action in human cells. Herein, we demonstrate that DMSO has ex-vivo anti-inflammatory activity using Escherichia coli- (E. coli) and herpes simplex virus-1 (HSV-1)-stimulated whole human blood. Specifically, we found that between 0.5%– 2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E₂ (PGE₂). However, a significant reduction in monocyte viability was also observed at 2% DMSO, suggesting a narrow window of efficacy. Anti-inflammatory concentrations of DMSO suppressed E. coli-induced ERK1/2, p38, JNK and Akt phosphorylation, suggesting DMSO acts on these signaling pathways to suppress inflammatory cytokine/chemokine production. Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth. Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood. Thus, while we cannot confirm the efficacy of DMSO as an anti-cancer agent, the use of DMSO in arthritis warrants further investigation to ascertain its therapeutic potential.     

Distribution dynamics of South American savanna birds in response to Quaternary climate change

Several lines of evidence suggest that savannas currently distributed disjointedly in the southern and northern portions of South America might have been connected and disconnected many times during the Quaternary climatic fluctuations. Here, we investigated how climate change since the Last Interglacial may have modified the distribution of bird species associated with South American savannas. We evaluated the connections between South America's savannas using 10 broadly distributed species and the impact of climate changes in community composition using 18 species endemic to Cerrado. We fit ecological niche models to each of the 28 bird species to compare the potential distribution patterns for the Last Interglacial (120 kyr BP), the Last Glacial Maximum (21 kyr BP) and the present. Our results corroborated hypotheses of past connections between northern and southern blocks of savannas through three hypothetical corridors that existed along the Andes, Atlantic Coast and through central Amazonia. In addition, our results also suggested the existence of a fourth plausible corridor located along the Madeira River, crossing Amazonia from the southwest to the northeast. Finally, our analysis showed significant changes in the community composition dynamics of endemic Cerrado species. Our results further reinforce the notion that climate change has major impacts on the distribution of savanna species.     

Hyperadrenocorticism of calorie restriction contributes to its anti‐inflammatory action in mice

Calorie restriction (CR), which lengthens lifespan in many species, is associated with moderate hyperadrenocorticism and attenuated inflammation. Given the anti‐inflammatory action of glucocorticoids, we tested the hypothesis that the hyperadrenocorticism of CR contributes to its attenuated inflammatory response. We used a corticotropin‐releasing‐hormone knockout (CRHKO) mouse, which is glucocorticoid insufficient. There were four controls groups: CRHKO mice and wild‐type (WT) littermates fed either ad libitum (AL) or CR (60% of AL food intake), and three experimental groups: (a) AL‐fed CRHKO mice given corticosterone (CORT) in their drinking water titrated to match the integrated 24‐hr plasma CORT levels of AL‐fed WT mice, (b) CR‐fed CRHKO mice given CORT to match the 24‐hr CORT levels of AL‐fed WT mice, and (c) CR‐fed CHRKO mice given CORT to match the 24‐hr CORT levels of CR‐fed WT mice. Inflammation was measured volumetrically as footpad edema induced by carrageenan injection. As previously observed, CR attenuated footpad edema in WT mice. This attenuation was significantly blocked in CORT‐deficient CR‐fed CRHKO mice. Replacement of CORT in CR‐fed CRHKO mice to the elevated levels observed in CR‐fed WT mice, but not to the levels observed in AL‐fed WT mice, restored the anti‐inflammatory effect of CR. These results indicate that the hyperadrenocorticism of CR contributes to the anti‐inflammatory action of CR, which may in turn contribute to its life‐extending actions.     

Estimating site occupancy and detectability of the threatened partridge pigeon (Geophaps smithii) using camera traps

Since European settlement, many granivorous birds of northern Australia's savanna landscapes have declined. One such example, the partridge pigeon (Geophaps smithii), has suffered a significant range contraction, disappearing from at least half of its pre‐European range. Multiple factors have been implicated in this decline, including the loss of traditional Aboriginal burning practices, grazing by large exotic herbivores and predation by feral cats (Felis catus). While populations of partridge pigeon on the Tiwi Islands may be particularly important for the long‐term persistence of this species, they too may be at risk of decline. However, as a reliable method to detect this species has not yet been developed and tested, we lack the ability to identify, at an early stage, the species' decline in a given location or region. This severely limits our capacity to make informed management decisions. Here, we demonstrate that the standard camera trapping approach for native mammal monitoring in northern Australia attained an overall probability of detecting partridge pigeon greater than 0.98. We thus provide a robust estimate of partridge pigeon site occupancy (0.30) on Melville Island, the larger of the two main Tiwi Islands. The information presented here for the partridge pigeon represents a critical first step towards the development of optimal monitoring programmes with which to gauge population trajectories, as well as the response to remedial management actions. In the face of ongoing biodiversity loss, such baseline information is vital for management agencies to make informed decisions and should therefore be sought for as many species as possible.     

Diffuse and nonlinear imaging of multiscale vascular parameters for in vivo monitoring of preclinical mammary tumors

Diffuse optical imaging (DOI) techniques provide a wide‐field or macro assessment of the functional tumor state and have shown substantial promise for monitoring treatment efficacy in cancer. Conversely, intravital microscopy provides a high‐resolution view of the tumor state and has played a key role in characterizing treatment response in the preclinical setting. There has been little prior work in investigating how the macro and micro spatial scales can be combined to develop a more comprehensive and translational view of treatment response. To address this, a new multiscale preclinical imaging technique called diffuse and nonlinear imaging (DNI) was developed. DNI combines multiphoton microscopy with spatial frequency domain imaging (SFDI) to provide multiscale data sets of tumor microvascular architecture coregistered within wide‐field hemodynamic maps. A novel method was developed to match the imaging depths of both modalities by utilizing informed SFDI spatial frequency selection. An in vivo DNI study of murine mammary tumors revealed multiscale relationships between tumor oxygen saturation and microvessel diameter, and tumor oxygen saturation and microvessel length (|Pearson's ρ| ≥ 0.5, P < 0.05). Going forward, DNI will be uniquely enabling for the investigation of multiscale relationships in tumors during treatment.      

The effects of different cold‐temperature regimes on development,growth, and susceptibility to an abiotic and biotic stressor

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