Purpose
To measure the dynamics of recruitment and the hemodynamic status during a sustained inflation recruitment maneuver (RM) in order to determine the optimal duration of RM in acute respiratory ...distress syndrome (ARDS) patients.
Methods
This prospective study was conducted in a 12-bed intensive care unit (ICU) in a general hospital. A 40 cmH
2
O sustained inflation RM maintained for 30 s was performed in 50 sedated ventilated patients within the first 24 h of meeting ARDS criteria. Invasive arterial pressures, heart rate, and SpO
2
were measured at 10-s intervals during the RM. The volume increase during the RM was measured by integration of the flow required to maintain the pressure at 40 cmH
2
O, which provides an estimation of the volume recruited during the RM. Raw data were corrected for gas consumption and fitted with an exponential curve in order to determine an individual time constant for the volume increase.
Results
The average volume increase and time constant were 210 ± 198 mL and 2.3 ± 1.3 s, respectively. Heart rate, diastolic arterial pressure, and SpO
2
did not change during or after the RM. Systolic and mean arterial pressures were maintained at 10 s, decreased significantly at 20 and 30 s during the RM, and recovered to the pre-RM value 30 s after the end of the RM (ANOVA,
p
< 0.01).
Conclusions
In early-onset ARDS patients, most of the recruitment occurs during the first 10 s of a sustained inflation RM. However, hemodynamic impairment is significant after the tenth second of RM.
The present work aimed at optimising the design and operation of char utilization as a low cost catalyst for tars reforming. The effect of temperature, tars composition, light hydrocarbons ...composition, steam content and type of reformer on the conversion of tars and light hydrocarbons into additional syngas using sorted municipal solid waste (MSW)—derived char was systematically monitored. Reforming tests were carried out using industrial primary syngas produced by air gasification of wood chips and MSW-RDF in a commercial fluidized bed gasifier. Up to 85% of tars present in the primary syngas have been converted to permanent gases at 871 °C, while passing through the catalytic fixed bed of char, for 1.4 s, at atmospheric pressure and syngas space velocities in the 3500–4000/h relative to the char in the bed (0.82 NL/g h). Content of multi-ring aromatics decreased following the passage of the syngas through the char bed leaving naphthalene and xylene as the predominant residuals. Propane, propylene and ethylene were completely converted. Up to 30% methane conversion was reached at 925 °C while ethane conversion was only occurring under high steam content of 65 vol%.
Graphical Abstract
In most organisms, the primary function of homologous recombination (HR) is to allow genome protection by the faithful repair of DNA double-strand breaks. The vital step of HR is the search for ...sequence homology, mediated by the RAD51 recombinase, which is stimulated further by proteins mediators such as the tumor suppressor BRCA2. The biochemical interplay between RAD51 and BRCA2 is unknown in Leishmania or Trypanosoma. Here we show that the Leishmania infantum BRCA2 protein possesses several critical features important for the regulation of DNA recombination at the genetic and biochemical level. A BRCA2 null mutant, generated by gene disruption, displayed genomic instability and gene-targeting defects. Furthermore, cytological studies show that LiRAD51 can no longer localize to the nucleus in this mutant. The Leishmania RAD51 and BRCA2 interact together and the purified proteins bind single-strand DNA. Remarkably, LiBRCA2 is a recombination mediator that stimulates the invasion of a resected DNA double-strand break in an undamaged template by LiRAD51 to form a D-loop structure. Collectively, our data show that LiBRCA2 and LiRAD51 promote HR at the genetic and biochemical level in L. infantum, the causative agent of visceral leishmaniasis.
The bradykinin (BK) B1 receptor is an attractive target for the treatment of chronic pain and inflammation. Starting from a dual B1 and B2 antagonist, novel antagonists were designed that display ...low-nanomolar affinity for human B1 receptor and selectivity over B2. Initially, potent imidazoline derivatives were studied, but these compounds suffered from low bioavailability. This issue could be overcome by the use of less basic amino derivatives leading to orally active compounds.
The efficacy of intravenous immunoglobulins (IVIg) in patients with autoimmune diseases (AID) has been known for several decades. Majority of these patients received IVIg in hospital. A retrospective ...study was conducted in 22 centers in France to evaluate the feasibility of the administration of Tegeline, an IVIg from LFB Biomedicaments, and assess its safety at home, compared to in hospital, in patients with AID. The included patients were at least 18 years old, suffering from AID, and treated with at least 1 cycle of Tegeline at home after receiving 3 consecutive cycles of hospital-based treatment with Tegeline at a dose between 1 and 2 g/kg/cycle. Forty-six patients with AID, in most cases immune-mediated neuropathies, received a total of 138 cycles of Tegeline in hospital and then 323 at home. Forty-five drug-related adverse events occurred in 17 patients who received their cycles at home compared to 24 adverse events in hospital in 15 patients. Serious adverse events occurred in 3 patients during home treatment, but they were not life-threatening and did not lead to discontinuation of Tegeline. Forty-five patients continued their treatment with Tegeline at home or in hospital; 39 (84.8%) were still receiving home treatment at the end of the study. In conclusion, the study demonstrates the good safety profile of Tegeline administered at home at high doses in patients with AID who are eligible for home administration of Tegeline.
Phenolic compounds contribute to the micronutrient composition of pasture, which in turn may affect animal product composition. To assess the importance and variations in content of these compounds, ...the polyphenolic and botanical compositions of 24 permanent pastures located in one lowland and two upland regions were studied at equivalent stages of growth. Phenolic fractions were characterized and quantified using HPLC-PDA-ESI-QToF, and the total content was determined by colorimetry over each whole pasture. A rise in altitude was accompanied by a marked increase in total phenolic content, linked to changes in botanical composition, but did not have any influence on the distribution according to molecular class. For all of the pastures, significantly different patterns due to qualitative and quantitative differences among the 92 separate peaks were observed with 31 compounds identified. The involvement of certain plants in the variations of content and composition in phenolic compounds of pastures was statistically evaluated.
Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and ...PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.
A number of recent reports have described the isolation and characterization of
Brucella strains from a wide variety of marine mammals such as seals, porpoises, dolphins and a minke whale. These ...strains were identified as brucellae by conventional typing tests. However, their overall characteristics were not assimilable to those of any of the six currently recognized
Brucella species and it was suggested that they comprise a new nomen species to be called ˈ
Brucella marisˈ. In the present study we analysed DNA polymorphism at the
omp2 locus of 33 marine mammal
Brucella strains isolated from seals, dolphins, porpoises and an otter. The
omp2 locus contains two gene copies (named
omp2a and
omp2b) coding for porin proteins and has been found particularly useful for molecular typing and identification of
Brucella at the species, biovar, or strain level. PCR-restriction fragment length polymorphism (RFLP) and DNA sequencing showed that strains isolated from dolphins and porpoises carry two
omp2b gene copies instead of one
omp2a and one
omp2b gene copy or two similar
omp2a gene copies reported in the currently recognized species. This observation was also recently made for a minke whale
Brucella isolate. The otter and all seal isolates except one were shown to carry one
omp2a and one
omp2b gene copy as encountered in isolates from terrestrial mammals. By PCR-RFLP of the
omp2b gene, a specific marker was detected grouping the marine mammal
Brucella isolates. Although marine mammal
Brucella isolates may represent a separate group from terrestrial mammal isolates based on
omp2b sequence constructed phylogenetic trees, the divergence found between their
omp2b and also between their
omp2a nucleotide sequences indicates that they form a more heterogeneous group than isolates from terrestrial mammals. Therefore, grouping the marine mammal
Brucella isolates into one species ˈ
Brucella marisˈ seems inappropriate unless the currently recognized
Brucella species are grouped. With respect to the current classification of brucellae according to the preferential host, brucellae isolated from such diverse marine mammal species as seals and dolphins could actually comprise more than one species, and at least two new species,
B. pinnipediae and
B. cetaceae, could be compatible with the classical criteria of host preferentialism and DNA polymorphism at their
omp2 locus.