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We tested whether the combination of a reduced dose of a local anesthetic (LA) with an opioid compared with a standard dose of the same LA alone guaranteed adequate intraoperative anesthesia and postoperative analgesia and decreased LA-related adverse effects. We systematically searched (to November 2012) for randomized comparisons of combinations of a reduced dose of an LA with a concomitant opioid (experimental) with a standard dose of the LA alone (control) in adults undergoing surgery with single-injection intrathecal anesthesia without general anesthesia. We included 28 trials (1393 patients). In experimental groups, the median decrease in LA doses was 40% (range, 12%–70%). There was no difference between experimental and control groups in the need for intraoperative opioids or general anesthesia for failed block or in the duration of postoperative analgesia. With experimental interventions, there was evidence of a reduction in the duration of motor blockade postoperatively (average, −50 minutes), time to discharge from hospital or PACU (−33 minutes), time to ambulation (−28 minutes), and time to urination (−14 minutes). There was also evidence of a decrease in the risk of shivering (risk ratio [RR]: 0.26; 95% confidence interval [CI]: 0.12–0.56), nausea (RR: 0.45; 95% CI: 0.31–0.66), and arterial hypotension (RR: 0.52; 95% CI: 0.35–0.78). The risk of pruritus was increased (RR: 11.7; 95% CI: 6.2–21.9). Adding an opioid to a reduced dose of an intrathecal LA can decrease LA-related adverse effects and improve recovery from the spinal block without compromising intraoperative anesthesia or duration of postoperative analgesia.  相似文献   
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Background

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with vascular, fibrotic and immune changes of skin and some internal organs. Anti-heterogeneous nuclear ribonucleoproteins (anti-hnRNP) were found in SSc patients.

Aim of the work

To assess anti-hnRNP A1 and A2 autoantibodies in limited SSc patients and to find their relation to clinical and hand radiographic characteristics.

Patients and methods

26 limited SSc patients and 16 matched control were studied. Skin thickness was scored according to the modified Rodnan skin score method (mRss) and radiologic examination by plain X-ray of the hand and wrist was performed anti-hnRNP A1 and A2 were measured in patients and control.

Results

All patients were females with a mean age of 37.5 ± 11.24 years and mean disease duration of 7.84 ± 1.19 years. 96.2% of cases showed juxta-articular osteoporosis, 38.5% with marginal erosions, 73.1% with surface erosions, 42.3% with subchondral cyst, 42.3% with metacarpophalangeal subluxation, 11.5% with marginal sclerosis, 80.8% with resorption of distal phalanges, 38.5% with resorption of distal ulna and 34.6% with calcinosis. Anti-hnRNPA1 was positive in all the patients but the anti-hnRNPA2 was positive in 21 (80.8%). Anti-hnRNP A1 and A2 showed significant difference between patients and control (5.66 ± 4.18 ng/ml vs 2.88 ± 0.82; p < 0.01 and 1.82 ± 0.36 vs 0.73 ± 0.08; p < 0.02, respectively). There was no significant correlation between the markers with the mRss or radiographic changes.

Conclusion

Joint affection in SSc is more frequent than expected. Anti-hnRNP A1 and anti hnRNP A2 antigens may be useful markers for SSc patient although no significant relation was found with radiologic findings.  相似文献   
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Chloride ion–pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation–diffusion process upon light-triggered retinal isomerization.

Chloride ion (Cl) concentration in some bacterial cells is regulated by rhodopsin proteins, generally known as halorhodopsin, or hR. These proteins use light energy to pump Cl into cells (1, 2). Light is harvested by a molecule of retinal, covalently linked to an essential lysine residue in the seventh transmembrane helix of GPCR-like (G protein–coupled receptor) proteins. Light activation causes retinal to isomerize from the all-trans to the 13-cis configuration. This change triggers subsequent conformational changes throughout the rhodopsin molecule and releases chloride into the cytoplasm. Retinal thermally relaxes to the all-trans configuration within milliseconds and is then ready for the next photocycle. Cl ions are transported from the extracellular (EC) side to the cytoplasmic (CP) side during each photocycle (3, 4).Light-driven ion-pumping rhodopsin can be used to develop artificial solar energy harvesting and optogenetics (58), but the molecular mechanism must be understood in detail for such applications. Despite the importance of hR, our current experimental data concerning the structure and dynamics of the protein remain very limited. A related protein, proton (H+)-pumping bacteriorhodopsin (bR) discovered in the early 1970s, has been extensively studied by multiple methods, including time-resolved spectroscopy, crystallography, mutagenesis, and computer simulation (912). In particular, recent studies using time-resolved serial femtosecond crystallography (TR-SFX) methods performed at X-ray free-electron laser (XFEL) facilities allow three-dimensional (3D) visualization of retinal isomerization and associated local conformational changes. These changes are accompanied by movement of protons from a donor aspartate group to an acceptor aspartate (1315). However, the central component of this process, the transported H+, is difficult to observe by X-ray crystallography and could not be directly traced in bR TR-SFX studies. Recently, a breakthrough was reported in a study on the sodium-pumping rhodopsin KR2 (K. eikastus rhodopsin 2), in which electron density signals of Na+ uptake were observed at Δt = 1 ms after laser illumination (16).Cl, a strong X-ray scatterer, can be directly observed from electron density maps. These maps provide first-hand information on the movement of ions as being transported within short timescales after light activation. Furthermore, hR and bR presumably share a common molecular mechanism despite transporting ions in opposite directions. A close relationship is strongly implied by the interconversion of the function of two rhodopsins. Outward H+-pumping bR can be converted to an inward Cl pump by changing a single residue (D85T) (17), while hR from the cyanobacterium, Mastigocladopsis repens, is reported to pump protons after a single mutation (T74D) (18). The chloride pump can therefore serve as a system analogous to the proton transporter and provide valuable information that is difficult to obtain directly from bR.In this study, we focus on chloride ion–pumping rhodopsin (ClR) from the marine flavobacterium Nonlabens marinus S1-08T (19). The conserved DTD motif (Asp85-Thr89-Asp96) of the bR family, residues 85, 89, and 96, is replaced by an NTQ motif (Asn98- Thr102-Gln109) in ClR (Fig. 1). The sequence identity of ClR and canonical bR from Halobacterium salinarum is only 27%, but the two proteins, nevertheless, have highly similar structures, including the disposition of the retinal chromophore. ClR structures at cryogenic and room temperatures clearly reveal an architecture composed of seven transmembrane helices (TM A to G) (2, 20, 21). The retinal is covalently linked to the Nζ atom of the Lys235 located on TM-G. Anomalous diffraction signals of the Br identify a stable binding site near the protonated Schiff base (PSB) and a plausible exit site on the CP side (Fig. 1A). Buried water molecules and locations of cavities inside ClR suggest a pathway for Cl uptake on the EC side, but the molecular mechanism for light-triggered Cl pumping remains obscure. Upon light activation, the Cl tightly held near the PSB must break free from its hydrogen bonding network (Fig. 1B). It then passes through a hydrophobic region to reach the CP side (Fig. 1C). Crystal structures of ClR were previously determined with crystals under continuous illumination of visible laser light. Intriguingly, these steady-state models revealed unexpected movement of the retinal, without indication of photo-isomerization (22). Steady-state measurements, which show averages of mixed states, are thus of limited use in deciphering the molecular mechanism of light-driven Cl pumping.Open in a separate windowFig. 1.Structure of ClR and a plausible pathway of Cl transport. (A) Cross-sections of ClR with the backbone structure shown in cartoon representation. Transmembrane helices are marked using letters A through G, and the C-terminal helix H in the cytoplasm is also indicated. Surfaces are clipped to show the cross-section colored in yellow and the model being sliced and then opened about the axis near the helix E. Water molecules and Cl ions are shown as red- and green-colored spheres. Blue curves indicate the path of ion entering ClR and the principal pumping direction after passing retinal. (B) Key residues near the Cl ion and retinal, together with the NTQ motif shown in stick representation. (C) Residues that form a hydrophobic region between the retinal and the cytoplasm are highlighted in ball-and-stick representation. The red arrow points to a major barrier that Cl needs to overcome. ClR backbone is shown in cartoon representation, with residues colored based on hydrophobicity (the blue to red spectrum corresponds to the hydrophobicity scale from hydrophilic to hydrophobic).  相似文献   
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