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811.
In this study we aimed to assess and compare the analgesic effects of orally administered sucrose, dextrose, dextrose or sucrose followed by a pacifier, and sterile water during minor painful procedures in neonates. One hundred thirty-eight healthy term newborn infants were enrolled in this prospective study. They received either sweet solutions or sweet solutions followed by pacifiers before the heel prick (group 1, dextrose 12.5%; group 2, dextrose 12.5% followed by a pacifier; group 3, sucrose 12.5%; group 4, sucrose 12.5% followed by a pacifier; and group 5, sterile water). The median values for crying time and the pain scores performed according to the neonatal facial coding system were recorded. The median crying times were 16.5, 55, 92.5, 102, and 132 seconds in groups 4, 2, 3, 1, and 5, respectively (P = .0001). The pain scores showed that babies in group 4 had significantly lower scores followed by groups 2, 3, 1, and 5 (P = .0001). Although group 4 had a lower pain score and shorter crying time than group 2, the difference was not statistically significant (P = .27 and P = .39). In conclusion, 12.5% dextrose or sucrose followed by a pacifier was found to be superior to dextrose only and sucrose only solutions in pain relief; sucrose followed by a pacifier resulted in lower pain scores and shorter crying time than dextrose when combined with a pacifier. The antinociceptive effect of sweet solutions can be enhanced with a pacifier.  相似文献   
812.
    
Pancreatic cancer is characterized by a high mortality rate and unfavorable prognosis. This is primarily attributed to poor accumulation of therapeutic agents at the target site due to the presence of a highly complex tumor microenvironment surrounding the pancreatic cancer tissue. However, a promising avenue for targeted drug delivery has emerged in the form of stimuli-responsive materials. These advanced nanocarriers, encompassing both external and internal stimuli-responsive nanoparticles, can be formulated to control the release of therapeutic agents precisely in response to specific activation. By harnessing external stimuli such as light, ultrasound, or magnetic fields, as well as intrinsic biological triggers including pH, redox potential, hypoxia, and temperature, these nanomaterials exhibit ‘intelligent’ and selective responses within complex biological environments. These responsive nanoparticles have been shown to address challenges associated with poor vascularity and thick desmoplastic stromal layers, which are hallmarks of pancreatic cancer, by promoting enhanced drug accumulation and release at the target site relative to conventional therapy. This work explores the design strategies for advanced stimuli-responsive nanomaterials, integrating both internal and external stimuli, with the potential to enhance drug delivery efficacy in pancreatic cancer. It addresses the challenges and prospects in their development and offers insights for future clinical applications.  相似文献   
813.
    
BackgroundUnlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain.MethodsCortex was made susceptible to CSD with partial inhibition of Na+/K+-ATPase by epidural application of a low concentration of Na+/K+-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down α2 subunit of Na+/K+-ATPase, which is crucial for K+ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K+ changes were monitored in vivo electrophysiologically and a K+-sensitive fluoroprobe (IPG-4), respectively.ResultsAfter priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na+/K+-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na+/K+-ATPase hypofunction, extracellular K+ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K+ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K+ uptake was not sufficiently suppressed as with ouabain.ConclusionsNormal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K+ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.  相似文献   
814.

Objective

Rheumatoid arthritis (RA) is a heterogeneous disease that exhibits a complex genetic component. Previous RA genome scans confirmed the involvement of the HLA region and generated data on suggestive signals at non‐HLA regions, albeit with few overlaps in findings between studies. The present study was undertaken to detect potential RA gene regions and to estimate the number of true RA gene regions, taking into account the heterogeneity of RA, through performance of a dense genome scan.

Methods

In a study of 88 French Caucasian families (105 RA sibpairs), 1,088 microsatellite markers were genotyped (3.3‐cM genome scan), and a multipoint model‐free linkage analysis was performed. The statistical assessment of the results relied on 10,000 computer simulations. A covariate‐based multipoint model‐free linkage analysis was performed on the locations of regions with suggestive evidence for linkage.

Results

Involvement of the HLA region was strongly confirmed (P = 6 × 10−5), and 19 non‐HLA regions showed suggestive evidence for linkage (P < 0.05); 9 of these overlapped with regions suggested in other published RA genome scans. A routine 12‐cM genome scan with the same families would have detected only 7 of the 19 regions, including only 4 of the 9 overlapping regions. From the 10,000 computer simulations, we estimated that 8 ± 4 regions (mean ± SD) were true‐positives. RA covariate–based analysis provided additional linkage evidence for 3 regions, with age at disease onset, erosions, and HLA–DRB1 shared epitope as covariates.

Conclusion

The results of this study provide evidence of 19 non‐HLA RA gene regions, with an estimate of 8 ± 4 as true‐positives, and provide additional evidence for 3 regions from covariate‐based analysis.
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