62 research outputs found
Chronic Opioid Use in Women Following Hysterectomy: Patterns and Predictors
Background: Most women are prescribed an opioid after hysterectomy. The goal of this study was to determine the association between initial opioid prescribing characteristics and chronic opioid use after hysterectomy.
Methods: This study included women enrolled in a commercial health plan who had a hysterectomy between 1 July 2010 and 31 March 2015. We used trajectory models to define chronic opioid use as patients with the highest probability of having an opioid prescription filled during the 6 months postâsurgery. A multivariable logistic regression was applied to examine the association between initial opioid dispensing (amount prescribed and duration of treatment) and chronic opioid use after adjusting for potential confounders.
Results: A total of 693 of 50â127 (1.38%) opioidânaĂŻve women met the criteria for chronic opioid use following hysterectomy. The baseline variables and initial opioid prescription characteristics predicted the pattern of longâterm opioid use with moderate discrimination (c statistic = 0.70). Significant predictors of chronic opioid use included initial opioid daily dose (â„60âMME vs \u3c40âMME, aOR: 1.43, 95% CI: 1.14â1.79) and days\u27 supply (4â7âdays vs 1â3âdays, aOR: 1.28, 95% CI: 1.06â1.54; â„8âdays vs 1â3âdays, aOR: 1.41, 95% CI: 1.05â1.89). Other significant baseline predictors included older age, abdominal or laparoscopic/robotic hysterectomy, tobacco use, psychiatric medication use, back pain, and headache.
Conclusion: Initial opioid prescribing characteristics are associated with the risk of chronic opioid use after hysterectomy. Prescribing lower daily doses and shorter days\u27 supply of opioids to women after hysterectomy may result in lower risk of chronic opioid use
Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development
Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease
MyD88 Is Required for Protection from Lethal Infection with a Mouse-Adapted SARS-CoV
A novel human coronavirus, SARS-CoV, emerged suddenly in 2003, causing approximately 8000 human cases and more than 700 deaths worldwide. Since most animal models fail to faithfully recapitulate the clinical course of SARS-CoV in humans, the virus and host factors that mediate disease pathogenesis remain unclear. Recently, our laboratory and others developed a recombinant mouse-adapted SARS-CoV (rMA15) that was lethal in BALB/c mice. In contrast, intranasal infection of young 10-week-old C57BL/6 mice with rMA15 results in a nonlethal infection characterized by high titer replication within the lungs, lung inflammation, destruction of lung tissue, and loss of body weight, thus providing a useful model to identify host mediators of protection. Here, we report that mice deficient in MyD88 (MyD88â/â), an adapter protein that mediates Toll-like receptor (TLR), IL-1R, and IL-18R signaling, are far more susceptible to rMA15 infection. The genetic absence of MyD88 resulted in enhanced pulmonary pathology and greater than 90% mortality by day 6 post-infection. MyD88â/â mice had significantly higher viral loads in lung tissue throughout the course of infection. Despite increased viral loads, the expression of multiple proinflammatory cytokines and chemokines within lung tissue and recruitment of inflammatory monocytes/macrophages to the lung was severely impaired in MyD88â/â mice compared to wild-type mice. Furthermore, mice deficient in chemokine receptors that contribute to monocyte recruitment to the lung were more susceptible to rMA15-induced disease and exhibited severe lung pathology similar to that seen in MyD88â/âmice. These data suggest that MyD88-mediated innate immune signaling and inflammatory cell recruitment to the lung are required for protection from lethal rMA15 infection
Investigation of Griffithsin's Interactions with Human Cells Confirms Its Outstanding Safety and Efficacy Profile as a Microbicide Candidate
Many natural product-derived lectins such as the red algal lectin griffithsin (GRFT) have potent in vitro activity against viruses that display dense clusters of oligomannose N-linked glycans (NLG) on their surface envelope glycoproteins. However, since oligomannose NLG are also found on some host proteins it is possible that treatment with antiviral lectins may trigger undesirable side effects. For other antiviral lectins such as concanavalin A, banana lectin and cyanovirin-N (CV-N), interactions between the lectin and as yet undescribed cellular moieties have been reported to induce undesirable side effects including secretion of inflammatory cytokines and activation of host T-cells. We show that GRFT, unlike CV-N, binds the surface of human epithelial and peripheral blood mononuclear cells (PBMC) through an exclusively oligosaccharide-dependent interaction. In contrast to several other antiviral lectins however, GRFT treatment induces only minimal changes in secretion of inflammatory cytokines and chemokines by epithelial cells or human PBMC, has no measureable effect on cell viability and does not significantly upregulate markers of T-cell activation. In addition, GRFT appears to retain antiviral activity once bound to the surface of PBMC. Finally, RNA microarray studies show that, while CV-N and ConA regulate expression of a multitude of cellular genes, GRFT treatment effects only minimal alterations in the gene expression profile of a human ectocervical cell line. These studies indicate that GRFT has an outstanding safety profile with little evidence of induced toxicity, T-cell activation or deleterious immunological consequence, unique attributes for a natural product-derived lectin
Large Tandem, Higher Order Repeats and Regularly Dispersed Repeat Units Contribute Substantially to Divergence Between Human and Chimpanzee Y Chromosomes
Comparison of human and chimpanzee genomes has received much attention,
because of paramount role for understanding evolutionary step distinguishing us
from our closest living relative. In order to contribute to insight into Y
chromosome evolutionary history, we study and compare tandems, higher order
repeats (HORs), and regularly dispersed repeats in human and chimpanzee Y
chromosome contigs, using robust Global Repeat Map algorithm. We find a new
type of long-range acceleration, human-accelerated HOR regions. In peripheral
domains of 35mer human alphoid HORs, we find riddled features with ten
additional repeat monomers. In chimpanzee, we identify 30mer alphoid HOR. We
construct alphoid HOR schemes showing significant human-chimpanzee difference,
revealing rapid evolution after human-chimpanzee separation. We identify and
analyze over 20 large repeat units, most of them reported here for the first
time as: chimpanzee and human ~1.6 kb 3mer secondary repeat unit (SRU) and
~23.5 kb tertiary repeat unit (~0.55 kb primary repeat unit, PRU); human 10848,
15775, 20309, 60910, and 72140 bp PRUs; human 3mer SRU (~2.4 kb PRU); 715mer
and 1123mer SRUs (5mer PRU); chimpanzee 5096, 10762, 10853, 60523 bp PRUs; and
chimpanzee 64624 bp SRU (10853 bp PRU). We show that substantial
human-chimpanzee differences are concentrated in large repeat structures, at
the level of as much as ~70% divergence, sizably exceeding previous numerical
estimates for some selected noncoding sequences. Smeared over the whole
sequenced assembly (25 Mb) this gives ~14% human--chimpanzee divergence. This
is significantly higher estimate of divergence between human and chimpanzee
than previous estimates.Comment: 22 pages, 7 figures, 12 tables. Published in Journal of Molecular
Evolutio
In situ X-ray diffraction measurement of shock-wave-driven twinning and lattice dynamics
Pressure-driven shock waves in solid materials can cause extreme damage and deformation. Understanding this deformation and the associated defects that are created in the material is crucial in the study of a wide range of phenomena, including planetary formation and asteroid impact sites, the formation of interstellar dust clouds, ballistic penetrators, spacecraft shielding and ductility in high-performance ceramics. At the lattice level, the basic mechanisms of plastic deformation are twinning (whereby crystallites with a mirror-image lattice form) and slip (whereby lattice dislocations are generated and move), but determining which of these mechanisms is active during deformation is challenging. Experiments that characterized lattice defects have typically examined the microstructure of samples after deformation, and so are complicated by post-shock annealing and reverberations. In addition, measurements have been limited to relatively modest pressures (less than 100 gigapascals). In situ X-ray diffraction experiments can provide insights into the dynamic behaviour of materials, but have only recently been applied to plasticity during shock compression and have yet to provide detailed insight into competing deformation mechanisms. Here we present X-ray diffraction experiments with femtosecond resolution that capture in situ, lattice-level information on the microstructural processes that drive shock-wave-driven deformation. To demonstrate this method we shock-compress the body-centred-cubic material tantalum-an important material for high-energy-density physics owing to its high shock impedance and high X-ray opacity. Tantalum is also a material for which previous shock compression simulations and experiments have provided conflicting information about the dominant deformation mechanism. Our experiments reveal twinning and related lattice rotation occurring on the timescale of tens of picoseconds. In addition, despite the common association between twinning and strong shocks, we find a transition from twinning to dislocation-slip-dominated plasticity at high pressure (more than 150 gigapascals), a regime that recovery experiments cannot accurately access. The techniques demonstrated here will be useful for studying shock waves and other high-strain-rate phenomena, as well as a broad range of processes induced by plasticity
Is the meiofauna a good indicator for climate change and anthropogenic impacts?
Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research
Contribution of oxic methane production to surface methane emission in lakes and its global importance
Recent discovery of oxic methane production in sea and lake waters, as well as wetlands demands re-thinking of the global methane cycle and re-assessment of the contribution of oxic waters to atmospheric methane emission. Here we analysed system-wide sources and sinks of surface-water methane in a temperate lake. Using a mass balance analysis, we show that internal methane production in well-oxygenated surface water is an important source for surface-water methane during the stratified period. Combining our results and literature reports, oxic methane contribution to emission follows a predictive function of littoral sediment area and surface mixed layer volume. The contribution of oxic methane source(s) is predicted to increase with lake size, accounting for the majority (>50 %) of surface methane emission for lakes with surface areas >1 km2
Human growth disorders: molecular genetics of the growth hormoneâinsulin-like growth factor I axis
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