Perioperative use of dexmedetomidine is associated with reduction in postoperative analgesic requirements. This study examined whether dexmedetomidine added to i.v. patient-controlled analgesia (PCA) ...morphine could improve analgesia while reducing opioid-related side-effects.
In this double-blinded, randomized, controlled study, 100 women undergoing abdominal total hysterectomy were allocated to receive either morphine 1 mg ml−1 alone (Group M) or morphine 1 mg ml−1 plus dexmedetomidine 5 μg ml−1 (Group D) for postoperative i.v. PCA, which was programmed to deliver 1 ml per demand with a 5 min lockout interval and no background infusion. Cumulative PCA requirements, pain intensities, cardiovascular and respiratory variables, and PCA-related adverse events were recorded for 24 h after operation.
Compared with Group M, patients in Group D required 29% less morphine during the 0–24 h postoperative period and reported significantly lower pain levels from the second postoperative hour onwards and throughout the study. Whereas levels of sedation were similar between the groups at each observational time point, decreases in heart rate and mean blood pressure from presurgery baseline at 1, 2, and 4 h after operation were significantly greater in Group D (by a range of 5–7 beats min−1 and 10–13%, respectively). The 4–24 h incidence of nausea was significantly lower in Group D (34% vs 56.3%, P<0.05). There was no bradycardia, hypotension, oversedation, or respiratory depression.
The addition of dexmedetomidine to i.v. PCA morphine resulted in superior analgesia, significant morphine sparing, less morphine-induced nausea, and was devoid of additional sedation and untoward haemodynamic changes.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Autophagy is a fundamental cellular process that maintains normal function and structure of the cell. It can be induced during stress and serves as an adaptive response for cell survival. Normal ...kidneys have high metabolic demands yet are relatively hypoxic, especially in the medulla and papilla. Injury or ageing aggravates metabolic perturbation and activates autophagy in many types of renal cells. In the kidney, tubular epithelial cells consume the most energy due to active transport mechanisms and therefore are the most susceptible to injuries from hypoxic or low‐energy states. This brief review will summarize current understandings of the biological function and molecular regulation of epithelial autophagy during tubular injury and repair.
Full text
Available for:
DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
p66Shc is shown to negatively regulate the life span in mice through reactive oxygen species (ROS) production. Recent reports, however, revealed that p66Shc protein level is significantly elevated in ...several human cancer tissues and growth-stimulated carcinoma cells, suggesting a mitogenic and carcinogenic role for p66Shc. In this communication, we demonstrate for the first time that p66Shc mediates androgenic growth signals in androgen-sensitive human prostate cancer cells through mitochondrial ROS production. Growth stimulation of prostate cancer cells with 5alpha-dihydrotestosterone (DHT) is accompanied by increased p66Shc level and ROS production, which is abolished by antioxidant treatments. However, antioxidant treatments do not affect the transcriptional activity of androgen receptor (AR) as observed by its inability to block DHT-induced prostate-specific antigen expression, an AR-dependent correlate of prostate cancer progression. Elevated expression of p66Shc by cDNA transfection increases the basal cell proliferation and, thus, reduces additional DHT-induced cell proliferation. Furthermore, DHT increases the translocation of p66Shc into mitochondria and its interaction with cytochrome c. Conversely, both redox-negative p66Shc mutant (W134F), which is deficient in cytochrome c interaction, and p66Shc small interfering RNA decrease DHT-induced cell proliferation. These results collectively reveal a novel role for p66Shc-ROS pathway in androgen-induced prostate cancer cell proliferation and, thus, may play a role in early prostate carcinogenesis.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study utilized the Coupled Model Intercomparison Project Phase 6 (CMIP6) models to examine the simulations of equatorial ocean currents and explore their substantial influences on the systematic ...bias of westward‐extended sea surface temperature anomalies (SSTA) pattern during El Niño. The results show that models simulate an excessive westward ocean current field over the equatorial central Pacific in the mean state. It tends to suppress the equatorial eastward ocean current anomalies with their maximum centering over the equatorial western Pacific in the El Niño developing phase. As a consequence, an overestimated zonal advective feedback toward the maritime continent exists, subsequently inducing the biased westward extension of SSTA pattern. Our results show that the mean‐state performance of equatorial ocean currents plays a key role on simulations of El Niño evolution in CMIP6 models.
Plain Language Summary
El Niño is the warm phase of El Niño–Southern Oscillation, known as a coupled air–sea phenomenon with considerable interannual variability in the tropics. In recent decades, many climate models have been developed to help us better understand the potential dynamics of El Niño. This study emphasizes the role of dynamical processes related to ocean currents in affecting the behavior of El Niño patterns in a series of the latest released CMIP6 climate models. We find that models have a relatively large bias in simulating the equatorial ocean currents in the Pacific. With an extremely strong equatorial zonal current in mean‐state field, the maximum of zonal current anomalies tends to shift toward the equatorial western Pacific and enhances the corresponding oceanic feedback mechanism, which substantially contributes to the overestimated sea surface temperature anomalies during El Niño evolution.
Key Points
The Coupled Model Intercomparison Project Phase 6 (CMIP6) models simulate an excessive westward ocean current field over the equatorial central Pacific in the mean state
Overestimated zonal advective feedback in the warm pool region is the dominant factor for the westward extension of El Niño pattern
Mean‐state performance of equatorial ocean current field plays a key role on the simulations of El Niño evolution in CMIP6 models
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning ...their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa
Cu
O
after the quench of superconductivity by an infrared laser pulse. We observe a nonthermal response of the CDW order characterized by a near doubling of the correlation length within ≈1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDWs manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations.
Ambient noise tomography and multiple plane wave earthquake tomography are new methods of surface wave analysis that yield much more highly refined information about the crust and uppermost mantle ...than traditional surface wave techniques. Applied together to data observed at more than 300 broadband seismic stations from the Transportable Array component of the EarthScope USArray, these methods yield surface wave dispersion curves from 8 to 100 s period across the entire western United States with unprecedented resolution. We use the local Rayleigh wave phase speed curves to construct a unified isotropic 3‐D Vs model to a depth of about 150 km. Crustal and uppermost mantle features that underlie the western United States are revealed in striking relief. As the USArray continues to sweep eastward across the United States, the substructure of the entire country will be unveiled.
Nalbuphine, a mixed agonist–antagonist opioid, has a potential to attenuate the mu-opioid effects and to enhance the kappa-opioid effects. However, when morphine and nalbuphine are mixed together, ...the clinical interactions in different combining ratios on analgesic effect and adverse events are unknown.
This randomized, double-blind controlled study investigated five different combining ratios of morphine and nalbuphine in 311 patients undergoing gynaecologic operations. The concentrations morphine (mg ml−1)/nalbuphine (mg ml−1) were 1/0 in Group 1, 0.75/0.25 (ratio 1:3) in Group 2, 0.5/0.5 (ratio 1:1) in Group 3, 0.25/0.75 (ratio 3:1) in Group 4, and 0/1 in Group 5. Patient-controlled analgesia (PCA) requirement, postoperative pain, and adverse events were evaluated throughout the postoperative 24 h period.
Twenty-four hour PCA requirements were similar among the five groups. Verbal rating scores for pain were statistically higher in Groups 2 and 4 than in Group 3. The incidences of pruritus were higher in Group 1 (15.6%) than in Group 2 (6.2%), Group 3 (3.4%), Group 4 (1.6%), and Group 5 (0%). The incidences and severity of dizziness, nausea, and vomiting were not significantly different.
The interaction between morphine and nalbuphine in PCA admixture on analgesia is additive. Combinations of morphine and nalbuphine in PCA can decrease the incidence of pruritus, and the antipruritus effect is ratio-dependent. This may provide a novel combination strategy of opioid agonist and agonist–antagonist for postoperative pain management after gynaecologic surgery.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Motivation: As high-throughput transcriptome sequencing provides evidence for novel transcripts in many species, there is a renewed need for accurate methods to classify small genomic regions as ...protein coding or non-coding. We present PhyloCSF, a novel comparative genomics method that analyzes a multispecies nucleotide sequence alignment to determine whether it is likely to represent a conserved protein-coding region, based on a formal statistical comparison of phylogenetic codon models.
Results: We show that PhyloCSF's classification performance in 12-species Drosophila genome alignments exceeds all other methods we compared in a previous study. We anticipate that this method will be widely applicable as the transcriptomes of many additional species, tissues and subcellular compartments are sequenced, particularly in the context of ENCODE and modENCODE, and as interest grows in long non-coding RNAs, often initially recognized by their lack of protein coding potential rather than conserved RNA secondary structures.
Availability and Implementation: The Objective Caml source code and executables for GNU/Linux and Mac OS X are freely available at http://compbio.mit.edu/PhyloCSF
Contact:
mlin@mit.edu; manoli@mit.edu
Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not ...conformer-sensitive. We report on a gas-phase megaelectronvolt ultrafast electron diffraction investigation of α-phellandrene undergoing an electrocyclic ring-opening reaction. We directly imaged the evolution of a specific set of α-phellandrene conformers into the product isomer predicted by the Woodward-Hoffmann rules in real space and time. Our experimental results are in quantitative agreement with nonadiabatic quantum molecular dynamics simulations, which provide considerable detail of how conformation influences the time scale and quantum efficiency of photoinduced ring-opening reactions.
Hearing impairment in older adults is independently associated in longitudinal studies with accelerated cognitive decline and incident dementia, and in cross-sectional studies, with reduced volumes ...in the auditory cortex. Whether peripheral hearing impairment is associated with accelerated rates of brain atrophy is unclear. We analyzed brain volume measurements from magnetic resonance brain scans of individuals with normal hearing versus hearing impairment (speech-frequency pure tone average>25dB) followed in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging for a mean of 6.4years after the baseline scan (n=126, age 56–86years). Brain volume measurements were performed with semi-automated region-of-interest (ROI) algorithms, and brain volume trajectories were analyzed with mixed-effect regression models adjusted for demographic and cardiovascular factors. We found that individuals with hearing impairment (n=51) compared to those with normal hearing (n=75) had accelerated volume declines in whole brain and regional volumes in the right temporal lobe (superior, middle, and inferior temporal gyri, parahippocampus, p<.05). These results were robust to adjustment for multiple confounders and were consistent with voxel-based analyses, which also implicated right greater than left temporal regions. These findings demonstrate that peripheral hearing impairment is independently associated with accelerated brain atrophy in whole brain and regional volumes concentrated in the right temporal lobe. Further studies investigating the mechanistic basis of the observed associations are needed.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
