Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease.

OBJECTIVE: Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure. METHODS: Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension. RESULTS: CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001)). CONCLUSIONS: Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD

Experimental and computational investigation of co production and dispersion in an automotive repair shop

Carbon monoxide (CO), a highly toxic gas, is produced during the incomplete combustion of carbon-based fuels. In indoor environments, high CO concentrations constitute a serious occupational health hazard; this is especially true in the case of automotive repair shop (ARS) employees who are exposed on a daily basis to vehicle exhaust streams. The present study focuses on the experimental investigation and numerical simulation of CO production and dispersion inside an ARS facility. Detailed measurements of CO concentration, vehicle traffic and ventilation system velocities are performed; the obtained data are appropriately formulated to provide quantitative information for modelling purposes. A detailed Computational Fluid Dynamics simulation of the developing transient flow-field is performed. The numerical results are validated using the experimental data; an overall good qualitative and quantitative agreement is achieved. Aiming to improve the energy efficiency of the mechanical ventilation system, three alternative scenarios are investigated; it is shown that the utilization of a dynamic ventilation system may result in significant energy consumption benefits, while, at the same time, CO concentrations remain below the values suggested by current occupational health legislation. The obtained results may be utilized to assist the design of mechanical ventilation systems for ARS facilities

Fungal microbiota from rain water and pathogenicity of Fusarium species isolated from atmospheric dust and rainfall dust

In order to determine the presence of Fusarium spp. in atmospheric dust and rainfall dust, samples were collected during September 2007, and July, August, and October 2008. The results reveal the prevalence of airborne Fusarium species coming from the atmosphere of the South East coast of Spain. Five different Fusarium species were isolated from the settling dust: Fusarium oxysporum, F. solani, F. equiseti, F. dimerum, and F. proliferatum. Moreover, rainwater samples were obtained during significant rainfall events in January and February 2009. Using the dilution-plate method, 12 fungal genera were identified from these rainwater samples. Specific analyses of the rainwater revealed the presence of three species of Fusarium: F. oxysporum, F. proliferatum and F. equiseti. A total of 57 isolates of Fusarium spp. obtained from both rainwater and atmospheric rainfall dust sampling were inoculated onto melon (Cucumis melo L.) cv. Piñonet and tomato (Lycopersicon esculentum Mill.) cv. San Pedro. These species were chosen because they are the main herbaceous crops in Almeria province. The results presented in this work indicate strongly that spores or propagules of Fusarium are able to cross the continental barrier carried by winds from the Sahara (Africa) to crop or coastal lands in Europe. Results show differences in the pathogenicity of the isolates tested. Both hosts showed root rot when inoculated with different species of Fusarium, although fresh weight measurements did not bring any information about the pathogenicity. The findings presented above are strong indications that long-distance transmission of Fusarium propagules may occur. Diseases caused by species of Fusarium are common in these areas. They were in the past, and are still today, a problem for greenhouses crops in Almería, and many species have been listed as pathogens on agricultural crops in this region. Saharan air masses dominate the Mediterranean regions. The evidence of long distance dispersal of Fusarium spp. by atmospheric dust and rainwater together with their proved pathogenicity must be taken into account in epidemiological studies

Molecular Cloning and Sequence Analysis of a Novel P450 Gene Encoding CYP345D3 from the Red Flour Beetle, Tribolium castaneum

A novel cDNA clone encoding a cytochrome P450 gene has been isolated from the insecticide-susceptible strain of the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). The nucleotide sequence of the clone, designated CYP345D3, was determined. The cDNA is 1554 bp in length and contains an open reading frame from base pairs 32 to 1513, encoding a protein of 493 amino acid residues and a predicted molecular weight of 57466 Daltons. The putative protein contains the classic heme-binding sequence motif FxxGxxxCxG (residues 430–439) conserved among all P450 enzymes as well as other characteristic motifs of the cytochrome P450s. Comparison of the deduced amino acid sequence with other CYP members shows that CYP345D3 shares 91% identity with the previously published sequence of CYP345D1 from the T. castaneum genome project and the nucleotide sequence identity between them is less than 80%. Phylogenetic analysis of amino acid sequences from members of various P450 families indicated close phylogenetic relationship of CYP345D3 with CYP6 of other insects than those from mammals and amore distant relationship to P450 from other families. CYP345D3 was submitted to GenBank, accession number EU008544

Two experiments for the price of one? -- The role of the second oscillation maximum in long baseline neutrino experiments

We investigate the quantitative impact that data from the second oscillation maximum has on the performance of wide band beam neutrino oscillation experiments. We present results for the physics sensitivities to standard three flavor oscillation, as well as results for the sensitivity to non-standard interactions. The quantitative study is performed using an experimental setup similar to the Fermilab to DUSEL Long Baseline Neutrino Experiment (LBNE). We find that, with the single exception of sensitivity to the mass hierarchy, the second maximum plays only a marginal role due to the experimental difficulties to obtain a statistically significant and sufficiently background-free event sample at low energies. This conclusion is valid for both water Cherenkov and liquid argon detectors. Moreover, we confirm that non-standard neutrino interactions are very hard to distinguish experimentally from standard three-flavor effects and can lead to a considerable loss of sensitivity to \theta_{13}, the mass hierarchy and CP violation.Comment: RevTex 4.1, 23 pages, 10 figures; v2: Typos corrected, very minor clarifications; matches published version; v3: Fixed a typo in the first equation in sec. III

Treatment of an Intramammary Bacterial Infection with 25-Hydroxyvitamin D3

Deficiency of serum levels of 25-hydroxyvitamin D3 has been correlated with increased risk of infectious diseases such as tuberculosis and influenza. A plausible reason for this association is that expression of genes encoding important antimicrobial proteins depends on concentrations of 1,25-dihydroxyvitamin D3 produced by activated immune cells at sites of infection, and that synthesis of 1,25-dihydroxyvitamin D3 is dependent on the availability of 25-hydroxyvitamin D3. Thus, increasing the availability of 25(OH)D3 for immune cell synthesis of 1,25-dihydroxyvitamin D3 at sites of infection has been hypothesized to aid in clearance of the infection. This report details the treatment of an acute intramammary infection with infusion of 25-hydroxyvitamin D3 to the site of infection. Ten lactating cows were infected with in one quarter of their mammary glands. Half of the animals were treated intramammary with 25-hydroxyvitamin D3. The 25-hydroxyvitamin D3 treated animal showed significantly lower bacterial counts in milk and showed reduced symptomatic affects of the mastitis. It is significant that treatment with 25-hydroxyvitamin D3 reduced the severity of an acute bacterial infection. This finding suggested a significant non-antibiotic complimentary role for 25-hydroxyvitamin D3 in the treatment of infections in compartments naturally low in 25-hydroxyvitamin D3 such as the mammary gland and by extension, possibly upper respiratory tract infections

Arsenic on the Hands of Children after Playing in Playgrounds

Increasing concerns over the use of wood treated with chromated copper arsenate (CCA) in playground structures arise from potential exposure to arsenic of children playing in these playgrounds. Limited data from previous studies analyzing arsenic levels in sand samples collected from CCA playgrounds are inconsistent and cannot be directly translated to the amount of children’s exposure to arsenic. The objective of this study was to determine the quantitative amounts of arsenic on the hands of children in contact with CCA-treated wood structures or sand in playgrounds. We compared arsenic levels on the hands of 66 children playing in eight CCA playgrounds with levels of arsenic found on the hands of 64 children playing in another eight playgrounds not constructed with CCA-treated wood. The children’s age and duration of playtime were recorded at each playground. After play, children’s hands were washed in a bag containing 150 mL of deionized water. Arsenic levels in the hand-washing water were quantified by inductively coupled plasma mass spectrometry. Our results show that the ages of the children sampled and the duration of play in the playgrounds were similar between the groups of CCA and non-CCA playgrounds. The mean amount of water-soluble arsenic on children’s hands from CCA playgrounds was 0.50 μg (range, 0.0078–3.5 μg). This was significantly higher (p < 0.001) than the mean amount of water-soluble arsenic on children’s hands from non-CCA playgrounds, which was 0.095 μg (range, 0.011–0.41 μg). There was no significant difference in the amount of sand on the children’s hands and the concentration of arsenic in the sand between the CCA and non-CCA groups. The higher values of arsenic on the hands of children playing in the CCA playgrounds are probably due to direct contact with CCA-treated wood. Washing hands after play would reduce the levels of potential exposure because most of the arsenic on children’s hands was washed off with water. The maximum amount of arsenic on children’s hands from the entire group of study participants was < 4 μg, which is lower than the average daily intake of arsenic from water and food

Shedding light on the elusive role of endothelial cells in cytomegalovirus dissemination.

Cytomegalovirus (CMV) is frequently transmitted by solid organ transplantation and is associated with graft failure. By forming the boundary between circulation and organ parenchyma, endothelial cells (EC) are suited for bidirectional virus spread from and to the transplant. We applied Cre/loxP-mediated green-fluorescence-tagging of EC-derived murine CMV (MCMV) to quantify the role of infected EC in transplantation-associated CMV dissemination in the mouse model. Both EC- and non-EC-derived virus originating from infected Tie2-cre(+) heart and kidney transplants were readily transmitted to MCMV-naïve recipients by primary viremia. In contrast, when a Tie2-cre(+) transplant was infected by primary viremia in an infected recipient, the recombined EC-derived virus poorly spread to recipient tissues. Similarly, in reverse direction, EC-derived virus from infected Tie2-cre(+) recipient tissues poorly spread to the transplant. These data contradict any privileged role of EC in CMV dissemination and challenge an indiscriminate applicability of the primary and secondary viremia concept of virus dissemination

Identification, Characterization, and Expression of a Novel P450 Gene Encoding CYP6AE25 from the Asian Corn Borer, Ostrinia furnacalis

An allele of the cytochrome P450 gene, CYP6AE14, named CYP6AE25 (GenBank accession no. EU807990) was isolated from the Asian com borer, Ostrinia fumacalis (Guenée) (Lepidoptera: Pyralidae) by RT-PCR. The cDNA sequence of CYP6AE25 is 2315 bp in length and contains a 1569 nucleotides open reading frame encoding a putative protein with 523 amino acid residues and a predicted molecular weight of 59.95 kDa and a theoretical pI of 8.31. The putative protein contains the classic heme-binding sequence motif F××G×××C×G (residues 451–460) conserved among all P450 enzymes as well as other characteristic motifs of all cytochrome P450s. It shares 52% identity with the previously published sequence of CYP6AE14 (GenBank accession no. DQ986461) from Helicoverpa armigera. Phylogenetic analysis of amino acid sequences from members of various P450 families indicated that CYP6AE25 has a closer phylogenetic relationship with CYP6AE14 and CYP6B1 that are related to metabolism of plant allelochemicals, CYP6D1 which is related to pyrethroid resistance and has a more distant relationship to CYP302A1 and CYP307A1 which are related to synthesis of the insect molting hormones. The expression level of the gene in the adults and immature stages of O. furnacalis by quantitative real-time PCR revealed that CYP6AE25 was expressed in all life stages investigated. The mRNA expression level in 3rd instar larvae was 12.8- and 2.97-fold higher than those in pupae and adults, respectively. The tissue specific expression level of CYP6AE25 was in the order of midgut, malpighian tube and fatty body from high to low but was absent in ovary and brain. The analysis of the CYP6AB25 gene using bioinformatic software is discussed

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB