382 research outputs found
Validation of the slaughterhouse porcine heart model for ex-situ heart perfusion studies
Introduction: To validate slaughterhouse hearts for ex-situ heart perfusion studies, we compared cold oxygenated machine perfusion in less expensive porcine slaughterhouse hearts (N = 7) to porcine hearts that are harvested following the golden standard in laboratory animals (N = 6). Methods: All hearts received modified St Thomas 2 crystalloid cardioplegia prior to 4 hours of cold oxygenated machine perfusion. Hearts were perfused with homemade modified Steen heart solution with a perfusion pressure of 20-25 mmHg to achieve a coronary flow between 100-200 mL/min. Reperfusion and testing was performed for 4 hours on a normothermic, oxygenated diluted whole blood loaded heart model. Survival was defined by a cardiac output above 3 L with a mean aortic pressure above 60 mmHg. Results: Both groups showed 100% functional survival, with laboratory hearts displaying superior cardiac function. Both groups showed similar decline in function over time. Conclusion: We conclude that the slaughterhouse heart can be used as an alternative to laboratory hearts and provides a cost-effective method for future ex-situ heart perfusion studies
Plasmonically Enhanced Reflectance of Heat Radiation from Low-Bandgap Semiconductor Microinclusions
Increased reflectance from the inclusion of highly scattering particles at
low volume fractions in an insulating dielectric offers a promising way to
reduce radiative thermal losses at high temperatures. Here, we investigate
plasmonic resonance driven enhanced scattering from microinclusions of
low-bandgap semiconductors (InP, Si, Ge, PbS, InAs and Te) in an insulating
composite to tailor its infrared reflectance for minimizing thermal losses from
radiative transfer. To this end, we compute the spectral properties of the
microcomposites using Monte Carlo modeling and compare them with results from
Fresnel equations. The role of particle size-dependent Mie scattering and
absorption efficiencies, and, scattering anisotropy are studied to identify the
optimal microinclusion size and material parameters for maximizing the
reflectance of the thermal radiation. For composites with Si and Ge
microinclusions we obtain reflectance efficiencies of 57 - 65% for the incident
blackbody radiation from sources at temperatures in the range 400 - 1600
{\deg}C. Furthermore, we observe a broadbanding of the reflectance spectra from
the plasmonic resonances due to charge carriers generated from defect states
within the semiconductor bandgap. Our results thus open up the possibility of
developing efficient high-temperature thermal insulators through use of the
low-bandgap semiconductor microinclusions in insulating dielectrics.Comment: Main article (8 Figures and 2 Tables) + Supporting Information (8
Figures
KIM-1 and NGAL: new markers of obstructive nephropathy
Congenital obstructive nephropathy is the primary cause of chronic renal failure in children. Rapid diagnosis and initiation of the treatment are vital to preserve function and/or to slow down renal injury. The aim of our study was to determine whether urinary (u) kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be useful non-invasive biomarkers in children with congenital hydronephrosis (HN) caused by ureteropelvic junction obstruction. The study cohort consisted of 20 children with severe HN who required surgery (median age 2.16 years) and two control groups (control group 1: 20 patients with mild, non-obstructive HN; control group 2: 25 healthy children). All of the children had normal renal function. Immunoenzymatic ELISA commercial kits were used to measure uKIM-1 and uNGAL concentrations. The preoperative median uKIM-1/creatinine (cr.) and uNGAL levels were significantly greater in the children with severe HN than in both control groups. Three months after surgery, uNGAL had decreased significantly (p < 0.05) in the children with severe HN, but was still higher than that in control group 2 children (p < 0.05). Receiver operator characteristic analyses revealed a good diagnostic profile for uKIM-1 and uNGAL in terms of identifying a differential renal function of <40% in HN patients (area under the curve (AUC) 0.8 and 0.814, respectively) and <45% in all examined children (AUC 0.779 and 0.868, respectively). Based on these results, we suggest that increasing uNGAL and uKIM-1 levels are associated with worsening obstruction. Further studies are required to confirm a potential application of uKIM-1 and uNGAL as useful biomarkers for the diagnosis and progression of chronic kidney disease
The PE-PPE Domain in Mycobacterium Reveals a Serine α/β Hydrolase Fold and Function: An In-Silico Analysis
The PE and PPE proteins first reported in the genome sequence of Mycobacterium tuberculosis strain H37Rv are now identified in all mycobacterial species. The PE-PPE domain (Pfam ID: PF08237) is a 225 amino acid residue conserved region located towards the C-terminus of some PE and PPE proteins and hypothetical proteins. Our in-silico sequence analysis revealed that this domain is present in all Mycobacteria, some Rhodococcus and Nocardia farcinica genomes. This domain comprises a pentapeptide sequence motif GxSxG/S at the N-terminus and conserved amino acid residues Ser, Asp and His that constitute a catalytic triad characteristic of lipase, esterase and cutinase activity. The fold prediction and comparative modeling of the 3-D structure of the PE-PPE domain revealed a “serine α/β hydrolase” structure with a central β-sheet flanked by α-helices on either side. The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site. The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified. Our findings add to the growing list of serine hydrolases in mycobacterium, which are essential for the maintenance of their impermeable cell wall and virulence. These results provide the directions for the design of experiments to establish the function of PE and PPE proteins
First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector
The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ
Effective Rheology of Bubbles Moving in a Capillary Tube
We calculate the average volumetric flux versus pressure drop of bubbles
moving in a single capillary tube with varying diameter, finding a square-root
relation from mapping the flow equations onto that of a driven overdamped
pendulum. The calculation is based on a derivation of the equation of motion of
a bubble train from considering the capillary forces and the entropy production
associated with the viscous flow. We also calculate the configurational
probability of the positions of the bubbles.Comment: 4 pages, 1 figur
Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines?
<p>Abstract</p> <p>Background</p> <p>To optimize the fluid status of adult patients with severe malaria, World Health Organization (WHO) guidelines recommend the insertion of a central venous catheter (CVC) and a target central venous pressure (CVP) of 0-5 cmH<sub>2</sub>O. However there are few data from clinical trials to support this recommendation.</p> <p>Methods</p> <p>Twenty-eight adult Indian and Bangladeshi patients admitted to the intensive care unit with severe <it>falciparum </it>malaria were enrolled in the study. All patients had a CVC inserted and had regular CVP measurements recorded. The CVP measurements were compared with markers of disease severity, clinical endpoints and volumetric measures derived from transpulmonary thermodilution.</p> <p>Results</p> <p>There was no correlation between the admission CVP and patient outcome (p = 0.67) or disease severity (p = 0.33). There was no correlation between the baseline CVP and the concomitant extravascular lung water (p = 0.62), global end diastolic volume (p = 0.88) or cardiac index (p = 0.44). There was no correlation between the baseline CVP and the likelihood of a patient being fluid responsive (p = 0.37). On the occasions when the CVP was in the WHO target range patients were usually hypovolaemic and often had pulmonary oedema by volumetric measures. Seven of 28 patients suffered a complication of the CVC insertion, although none were fatal.</p> <p>Conclusion</p> <p>The WHO recommendation for the routine insertion of a CVC, and the maintenance of a CVP of 0-5 cmH<sub>2</sub>O in adults with severe malaria, should be reconsidered.</p
Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis
BACKGROUND: New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. METHODS: Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. RESULTS: A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. CONCLUSION: These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB
The impact of single and pairwise Toll-like receptor activation on neuroinflammation and neurodegeneration
Background Toll-like receptors (TLRs) enable innate immune cells to respond to
pathogen- and host-derived molecules. The central nervous system (CNS)
exhibits most of the TLRs identified with predominant expression in microglia,
the major immune cells of the brain. Although individual TLRs have been shown
to contribute to CNS disorders, the consequences of multiple activated TLRs on
the brain are unclear. We therefore systematically investigated and compared
the impact of sole and pairwise TLR activation on CNS inflammation and injury.
Methods Selected TLRs expressed in microglia and neurons were stimulated with
their specific TLR ligands in varying combinations. Cell cultures were then
analyzed by immunocytochemistry, FlowCytomix, and ELISA. To determine neuronal
injury and neuroinflammation in vivo, C57BL/6J mice were injected
intrathecally with TLR agonists. Subsequently, brain sections were analyzed by
quantitative real-time PCR and immunohistochemistry. Results Simultaneous
stimulation of TLR4 plus TLR2, TLR4 plus TLR9, and TLR2 plus TLR9 in microglia
by their respective specific ligands results in an increased inflammatory
response compared to activation of the respective single TLR in vitro. In
contrast, additional activation of TLR7 suppresses the inflammatory response
mediated by the respective ligands for TLR2, TLR4, or TLR9 up to 24 h,
indicating that specific combinations of activated TLRs individually modulate
the inflammatory response. Accordingly, the composition of the inflammatory
response pattern generated by microglia varies depending on the identity and
combination of the activated TLRs engaged. Likewise, neuronal injury occurs in
response to activation of only selected TLRs and TLR combinations in vitro.
Activation of TLR2, TLR4, TLR7, and TLR9 in the brain by intrathecal injection
of the respective TLR ligand into C57BL/6J mice leads to specific expression
patterns of distinct TLR mRNAs in the brain and causes influx of leukocytes
and inflammatory mediators into the cerebrospinal fluid to a variable extent.
Also, the intensity of the inflammatory response and neurodegenerative effects
differs according to the respective activated TLR and TLR combinations used in
vivo. Conclusions Sole and pairwise activation of TLRs modifies the pattern
and extent of inflammation and neurodegeneration in the CNS, thereby enabling
innate immunity to take account of the CNS diseases’ diversity
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