Artificial membrane-feeding techniques have replaced direct feeding on animals for the maintenance of malaria and arbovirus vectors in many laboratories. Membrane feeding facilitates controlled ...experimentation of pathogen transmission during mosquito feeding. Sheep blood is commonly used due to its availability and low cost. We evaluated the impact of blood source (human, guinea pig, sheep, and hamster via direct feeding) on feeding rates, adult survival, fecundity, hatching rates, and developmental times for five species of laboratory-colonized mosquitoes (Anopheles dirus, An. cracens, An. minimus, An. sawadwongporni, and Ae. aegypti). We found that feeding rates differ among blood sources within mosquito species. Survival, fecundity, and hatching rates were lower in all Anopheles species and Ae. aegypti after membrane feeding on sheep blood. Survival rates seven days post-feeding on sheep blood were significantly lower (P<0.05) for An. dirus (84.2%), An. minimus (67.2%), An. sawadwongporni (51.5%), and An. cracens (35.5%) relative to other blood sources. An. minimus and An. sawadwongporni laid no eggs by seven days post-feeding with sheep blood, while An. dirus and An. cracens produced significantly fewer numbers of eggs and demonstrated significantly lower hatching rates relative to what was observed with the other blood sources. These findings support the conclusion that sheep blood is not a suitable blood source for laboratory rearing of Anopheles spp.
CONTEXT Data are sparse on the effect of varying the durations of internal medicine attending physician ward rotations. OBJECTIVE To compare the effects of 2- vs 4-week inpatient attending physician ...rotations on unplanned patient revisits, attending evaluations by trainees, and attending propensity for burnout. DESIGN, SETTING, AND PARTICIPANTS Cluster randomized crossover noninferiority trial, with attending physicians as the unit of crossover randomization and 4-week rotations as the active control, conducted in a US university-affiliated teaching hospital in academic year 2009. Participants were 62 attending physicians who staffed at least 6 weeks of inpatient service, the 8892 unique patients whom they discharged, and the 147 house staff and 229 medical students who evaluated their performance. INTERVENTION Assignment to random sequences of 2- and 4-week rotations. MAIN OUTCOME MEASURES Primary outcome was 30-day unplanned revisits (visits to the hospital's emergency department or urgent ambulatory clinic, unplanned readmissions, and direct transfers from neighboring hospitals) for patients discharged from 2- vs 4-week within-attending-physician rotations. Noninferiority margin was a 2% increase (odds ratio OR of 1.13) in 30-day unplanned patient revisits. Secondary outcomes were length of stay; trainee evaluations of attending physicians; and attending physician reports of burnout, stress, and workplace control. RESULTS Among the 8892 patients, there were 2437 unplanned revisits. The percentage of 30-day unplanned revisits for patients of attending physicians on 2-week rotations was 21.2% compared with 21.5% for 4-week rotations (mean difference, –0.3%; 95% CI, –1.8% to +1.2%). The adjusted OR of a patient having a 30-day unplanned revisit after 2- vs 4-week rotations was 0.97 (1-sided 97.5% upper confidence limit, 1.07; noninferiority P = .007). Average length of stay was not significantly different (geometric means for 2- vs 4-week rotations were 67.2 vs 67.5 hours; difference, –0.9%; 95% CI, –4.7% to +2.9%). Attending physicians were more likely to score lower in their ability to evaluate trainees after 2- vs 4-week rotations by both house staff (41% vs 28% rated less than perfect; adjusted OR, 2.10; 95% CI, 1.50-3.02) and medical students (82% vs 69% rated less than perfect; adjusted OR, 1.41; 95% CI, 1.06-2.10). They were less likely to report higher scores of both burnout severity (16% vs 35%; adjusted OR, 0.39; 95% CI, 0.26-0.58) and emotional exhaustion (19% vs 37%; adjusted OR, 0.45; 95% CI, 0.31 to 0.64) after 2- vs 4-week rotations. CONCLUSIONS The use of 2-week inpatient attending physician rotations compared with 4-week rotations did not result in an increase in unplanned patient revisits. It was associated with better self-rated measures of attending physician burnout and emotional exhaustion but worse evaluations by trainees. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00930111
AlN/GaN heterostructures with 1700-cm 2 /V·s Hall mobility have been grown by molecular beam epitaxy on freestanding GaN substrates. Submicrometer gate-length (L G ) metal-oxide-semiconductor (MOS) ...high-electron-mobility transistors (HEMTs) fabricated from this material show excellent dc and RF performance. L G = 100 nm devices exhibited a drain current density of 1.5 A/mm, current gain cutoff frequency f T of 165 GHz, a maximum frequency of oscillation f max of 171 GHz, and intrinsic average electron velocity v e of 1.5 ×10 7 cm/s. The 40-GHz load-pull measurements of L G = 140 nm devices showed 1-W/mm output power, with a 4.6-dB gain and 17% power-added efficiency. GaN substrates provide a way of achieving high mobility, high v e , and high RF performance in AlN/GaN transistors.
Astrocyte activation is a common feature of neurodegenerative diseases. However, the ways in which dying neurons influence the activity of astrocytes is poorly understood. Receptor interacting ...protein kinase-3 (RIPK3) signaling has recently been described as a key regulator of neuroinflammation, but whether this kinase mediates astrocytic responsiveness to neuronal death has not yet been studied. Here, we used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease to show that activation of astrocytic RIPK3 drives dopaminergic cell death and axon damage. Transcriptomic profiling revealed that astrocytic RIPK3 promoted gene expression associated with neuroinflammation and movement disorders, and this coincided with significant engagement of damage associated molecular pattern (DAMP) signaling. In mechanistic experiments, we show that factors released from dying neurons signal through receptor for advanced glycation endproducts (RAGE) to induce astrocytic RIPK3 signaling, which conferred inflammatory and neurotoxic functional activity. These findings highlight a mechanism of neuron-glia crosstalk in which neuronal death perpetuates further neurodegeneration by engaging inflammatory astrocyte activation via RIPK3.
Recent discoveries of methyl-coenzyme M reductase-encoding genes (
) in uncultured archaea beyond traditional euryarchaeotal methanogens have reshaped our view of methanogenesis. However, whether any ...of these nontraditional archaea perform methanogenesis remains elusive. Here, we report field and microcosm experiments based on
C-tracer labeling and genome-resolved metagenomics and metatranscriptomics, revealing that nontraditional archaea are predominant active methane producers in two geothermal springs.
performed methanogenesis from methanol and may exhibit adaptability in using methylotrophic and hydrogenotrophic pathways based on temperature/substrate availability. A five-year field survey found
Nezhaarchaeota to be the predominant
-containing archaea inhabiting the springs; genomic inference and
expression under methanogenic conditions strongly suggested that this lineage mediated hydrogenotrophic methanogenesis in situ. Methanogenesis was temperature-sensitive , with a preference for methylotrophic over hydrogenotrophic pathways when incubation temperatures increased from 65° to 75°C. This study demonstrates an anoxic ecosystem wherein methanogenesis is primarily driven by archaea beyond known methanogens, highlighting diverse nontraditional
-containing archaea as previously unrecognized methane sources.
Abstract Background Hospitalists can use hand-carried echocardiography for accurate point-of-care information, but patient outcome data for its application are sparse. Methods We performed an ...unblinded, parallel-group randomized trial between July 2008 and March 2009 at one teaching hospital in Chicago, Illinois. We randomly assigned adult general medicine inpatients referred for standard echocardiography with indications investigatable by hand-carried echocardiography to care guided by hand-carried echocardiography or usual care. The main outcome measure was length of stay on the referring hospitalist's service. Secondary outcomes included a before-after analysis of reported changes in management due to hand-carried echocardiography and the diagnostic accuracy of hand-carried echocardiography. Results The difference in length of stay between 226 participants randomized to care guided by hand-carried echocardiography (geometric mean 46.1 hours, interquartile range 29.0-70.9 hours) and 227 participants randomized to usual care (46.9 hours, interquartile range 34.1-68.3 hours) corresponded to a 1.7% reduction in length of stay that was not statistically significant (95% confidence interval, −12.1 to 9.8%). In post hoc subgroup analyses, care guided by hand-carried echocardiography reduced length of stay in participants who were referred for heart failure ( P = .0008). Among participants who underwent both hand-carried and standard echocardiography, hospitalists changed management due to hand-carried echocardiography in 37%. Despite the favorable diagnostic accuracy of hand-carried echocardiography, most changes to the timing of hospital discharge occurred after standard echocardiography. Conclusion Hospitalist care guided by hand-carried echocardiography for unselected general medicine patients does not meaningfully affect length of stay. Whether or not it affects care quality remains unstudied.
The efficacy of a metofluthrin-impregnated net (MIN) known as the "Mushikonazu" on the house entry behavior of female Aedes aegypti and Anopheles dirus mosquitoes was evaluated using a semi-field ...50-m tunnel setup. While the MIN is labeled for the control of chironomids and moth flies, this study determined the feasibility of using the device, given its current construction and metofluthrin formulation, as a spatial repellent against mosquitoes. Sentinel and cone bioassays were used to determine the insecticidal effect of the MIN. A spatial activity index (SAI) was calculated to evaluate responses of the mosquitoes. For the spatial repellent evaluation against Ae. aegypti, the overall mean of SAI was slightly less than 0 at wk 1 after the MIN application and then decreased for the last 4 wk showing a preference to treatment tent. For An. dirus, the mean SAI at wk 1 was positive, indicating a presumed repellent effect of the MIN against An. dirus. For the subsequent 4 wk, the SAI was negative, indicating a preference for the MIN. Results suggested that the MIN may not be a promising approach to repel Ae. aegypti and An. dirus under field conditions in Thailand. However, it remains probable that the MIN may be effective as a spatial repellent if modifications are made to the metofluthrin concentration or formulation and/or the construction of the device.
There is a vital need to develop in vitro models of the developing human brain to recapitulate the biological effects that toxic compounds have on the brain. To model perineural vascular plexus ...(PNVP) in vitro, which is a key stage in embryonic development, human embryonic stem cells (hESC)‐derived endothelial cells (ECs), neural progenitor cells, and microglia (MG) with primary pericytes (PCs) in synthetic hydrogels in a custom‐designed microfluidics device are cocultured. The formation of a vascular plexus that includes networks of ECs (CD31+, VE‐cadherin+), MG (IBA1+), and PCs (PDGFRβ+), and an overlying neuronal layer that includes differentiated neuronal cells (βIII Tubulin+, GFAP+) and radial glia (Nestin+, Notch2NL+), are characterized. Increased brain‐derived neurotrophic factor secretion and differential metabolite secretion by the vascular plexus and the neuronal cells over time are consistent with PNVP functionality. Multiple concentrations of developmental toxicants (teratogens, microglial disruptor, and vascular network disruptors) significantly reduce the migration of ECs and MG toward the neuronal layer, inhibit formation of the vascular network, and decrease vascular endothelial growth factor A (VEGFA) secretion. By quantifying 3D cell migration, metabolic activity, vascular network disruption, and cytotoxicity, the PNVP model may be a useful tool to make physiologically relevant predictions of developmental toxicity.
Current models of in vitro brain development fail to mimic mechanisms in vivo, partly as they use animal‐derived matrices. The current study incorporates differentiated cell lines in a fabricated synthetic hydrogel in a microfluidics plate to recapitulate perineural vascular plexus in vivo. By analyzing endpoints such as growth factors, metabolites and 3D cell migration, this model predicts acute toxicity mechanisms.
Asgardarchaeota have been proposed as the closest living relatives to eukaryotes, and a total of 72 metagenome-assembled genomes (MAGs) representing six primary lineages in this archaeal phylum have ...thus far been described. These organisms are predicted to be fermentative heterotrophs contributing to carbon cycling in sediment ecosystems. Here, we double the genomic catalogue of Asgardarchaeota by obtaining 71 MAGs from a range of habitats around the globe, including the deep subsurface, brackish shallow lakes, and geothermal spring sediments. Phylogenomic inferences followed by taxonomic rank normalisation confirmed previously established Asgardarchaeota classes and revealed four additional lineages, two of which were consistently recovered as monophyletic classes. We therefore propose the names Candidatus Sifarchaeia class nov. and Ca. Jordarchaeia class nov., derived from the gods Sif and Jord in Norse mythology. Metabolic inference suggests that both classes represent hetero-organotrophic acetogens, which also have the ability to utilise methyl groups such as methylated amines, with acetate as the probable end product in remnants of a methanogen-derived core metabolism. This inferred mode of energy conservation is predicted to be enhanced by genetic code expansions, i.e., stop codon recoding, allowing the incorporation of the rare 21st and 22nd amino acids selenocysteine (Sec) and pyrrolysine (Pyl). We found Sec recoding in Jordarchaeia and all other Asgardarchaeota classes, which likely benefit from increased catalytic activities of Sec-containing enzymes. Pyl recoding, on the other hand, is restricted to Sifarchaeia in the Asgardarchaeota, making it the first reported non-methanogenic archaeal lineage with an inferred complete Pyl machinery, likely providing members of this class with an efficient mechanism for methylamine utilisation. Furthermore, we identified enzymes for the biosynthesis of ester-type lipids, characteristic of bacteria and eukaryotes, in both newly described classes, supporting the hypothesis that mixed ether-ester lipids are a shared feature among Asgardarchaeota.
PDF
