Corpus callosum alterations in very preterm infants: perinatal correlates and 2 year neurodevelopmental outcomes

The aim of this study was to relate altered corpus callosum (CC) integrity in 106 very preterm (VPT) infants (< 30 weeks' gestational age or < 1250 g birth weight) at term equivalent to perinatal predictors and neurodevelopmental outcomes at two years. T1 and diffusion magnetic resonance images were obtained. The CC was traced, and divided into six sub-regions for cross-sectional area and shape analyses. Fractional anisotropy, mean, axial and radial diffusivity were sampled within the CC, and probabilistic tractography was performed. Perinatal predictors were explored. The Bayley Scales of Infant Development (BSID-II) was administered at two years. Intraventricular hemorrhage was associated with a smaller genu and altered diffusion values within the anterior and posterior CC of VPT infants. White matter injury was associated with widespread alterations to callosal diffusion values, especially posteriorly, and radial diffusivity was particularly elevated, indicating altered myelination. Reduced CC tract volume related to lower gestational age, particularly posteriorly. Reduced posterior callosal skew was associated with postnatal corticosteroid exposure. This more circular CC was associated with delayed cognitive development. Higher diffusivity, particularly in splenium tracts, was associated with impaired motor development. This study elucidates perinatal predictors and adverse neurodevelopmental outcomes associated with altered callosal integrity in VPT infants.     

Efficient topical delivery of plasmid DNA to lung in vivo mediated by putative triggered, PEGylated pDNA nanoparticles

Non-viral vectors are considered safer than viral vectors and show clinical potential, but remain less efficient in terms of DNA delivery. Here we report how cationic liposomes, prepared from new cationic lipid, N′,N′,-dioctadecyl-N-4,8-diaza-10-aminodecanoylglycine amide (DODAG) and neutral lipid dioleoyl-l-α-phos-phatidylethanolamine (DOPE), can be formulated with plasmid DNA (pDNA) in the presence of stabilizer cholesteryl-oxycarbonylpolyethlylene glycol⁴⁶⁰⁰ (PEG⁴⁶⁰⁰-Chol) giving PEGylated pDNA nanoparticles (pDNA-ABC nanoparticles) that are proposed to be half-life triggered nanoparticles. In particular, the PEGylated pDNA nanoparticle formulation DODAG/DOPE/PEG⁴⁶⁰⁰-Chol (43:43:14, m/m/m) − pDNA (total lipid/pDNA ratio 4:1 w/w) (pTRANSplus nanoparticles) is shown to mediate efficient transfection of murine lung tissue in vivo. Levels of transfection compare well with the results of polyethylenimine (PEI) mediated pDNA transfection in vivo and even of adenovirus mediated transduction. Cryo-EM imaging indicates that pTRANSplus formulations are somewhat heterogeneous but do consist primarily of bilammellar lipoplex nanoparticles with a few multilammellar nanoparticle aggregates. Lung histology confirms that pTRANSplus mediated transfection in vivo targets substantially the epithelial cells of bronchii and bronchioli airway passages. The pTRANSplus nanoparticle system is a useful new starting point for nucleic acid therapeutic strategies to counter lung disorders such as viral infection and possibly cystic fibrosis.     

患者自控镇静用于眼底手术的临床研究

目的探讨球后阻滞眼底手术患者应用异丙酚和瑞芬太尼自控镇静(PCS)的优越性。方法42例择期球后阻滞眼底手术患者,随机分为3组:P组15例,应用1%异丙酚;R组15例,应用0.5%异丙酚+0.001%瑞芬太尼;C组12例,空白对照组。PCS组(P组、R组)采用爱朋全自动注药泵,选择负荷剂量+持续背景输注+PCS(LCP模式)静脉输注异丙酚和(或)瑞芬太尼。术中监测BP、HR、SpO2、RR、听觉诱发电位(AAI)、镇静评分(Ramsay评分)、患者合作评分、术者满意度,术后随访患者满意度和不良反应发生情况。结果三组术前情况差异无统计学意义。术后MAP、HR、SpO2和AAI差异无统计学意义(P>0.05)。R组RR显著低于P组、C组(P<0.05),PCS组的镇静评分、合作评分、满意度评分、球后阻滞疼痛评分明显优于C组(P<0.05),PCS组用药量个体差异较大。三组均无术后恶心、呕吐等现象。结论应用异丙酚、瑞芬太尼进行PCS可安全用于球后阻滞眼底手术,是一种适用于不同患者的较理想的方法。     

Cognitive intrusion of pain and catastrophic thinking independently explain interference of pain in the activities of daily living

Patients with musculoskeletal illness often report that pain interferes with their ability to engage in activities of daily living. Catastrophic thinking is consistently depicted as an important cognitive factor that hinders adjustment to pain. Current research has also shown that pain negatively impacts an individual's ability to maintain attention on the task at hand. While a measure of the experience of cognitive intrusion of pain (ECIP) has been recently developed to quantify the extent of that impact, little research has explored this issue in everyday settings. This study tested the mediating roles of cognitive intrusion of pain and pain catastrophizing scale (PCS) on the association of pain intensity with pain interference in 142 patients with upper-extremity musculoskeletal illness. We found that both cognitive intrusion of pain (b = 0.136, bootstrap SE = 0.048, 95% BCa CI [0.052, 0.245]) and pain catastrophizing (b = 0.114, bootstrap SE = 0.044, 95% BCa CI [0.047, 0.221]) partly and independently mediated the relationship between pain intensity and pain interference. Although comparable, the mediation effect of cognitive intrusion of pain was slightly larger than that of pain catastrophizing (25.7%, bootstrap SE = 0.094 vs. 21.5%, bootstrap SE = 0.080). Results suggest that pain sensations can interfere with activities of daily living through two distinct mechanisms. A combination of traditional cognitive behavioral therapy and mindfulness skills training targeting both pain catastrophizing and cognitive intrusion has the potential to decrease pain interference and help patients return to normal healthy living in spite of acute or persistent pain.     

Nanoparticles for skin penetration enhancement--a comparison of a dendritic core-multishell-nanotransporter and solid lipid nanoparticles

Nanosized particles are of growing interest for topical treatment of skin diseases to increase skin penetration of drugs and to reduce side effects. Effects of the particle structure and size were studied loading nile red to dendritic core-multishell (CMS) nanotransporters (20-30 nm) and solid lipid nanoparticles (SLNs, 150-170 nm). Interaction properties of CMS nanotransporters with the dye molecules--attachment to the carrier surface or incorporation in the carrier matrix--were studied by UV/Vis and parelectric spectroscopy. Pig skin penetration was studied ex vivo using a cream for reference. Interactions of SLN and skin were followed by scanning electron microscopy, internalisation of the particles by viable keratinocytes by laser scanning microscopy. Incorporating nile red into a stable dendritic nanoparticle matrix, dye amounts increased eightfold in the stratum corneum and 13-fold in the epidermis compared to the cream. Despite SLN degradation at the stratum corneum surface, SLN enhanced skin penetration less efficiently (3.8- and 6.3-fold). Viable human keratinocytes showed an internalisation of both nanocarriers. In conclusion, CMS nanotransporters can favour the penetration of a model dye into the skin even more than SLN which may reflect size effects.     

Gastric electrical stimulation for medically refractory gastroparesis

Background & aims:

This study investigated the efficacy of gastric electrical stimulation for the treatment of symptomatic gastroparesis unresponsive to standard medical therapy.

Methods:

Thirty-three patients with chronic gastroparesis (17 diabetic and 16 idiopathic) received continuous high-frequency/low-energy gastric electrical stimulation via electrodes in the muscle wall of the antrum connected to a neurostimulator in an abdominal wall pocket. After implantation, patients were randomized in a double-blind crossover design to stimulation ON or OFF for 1-month periods. The blind was then broken, and all patients were programmed to stimulation ON and evaluated at 6 and 12 months. Outcome measures were vomiting frequency, preference for ON or OFF, upper gastrointestinal tract symptoms, quality of life, gastric emptying, and adverse events.

Results:

In the double-blind portion of the study, self-reported vomiting frequency was significantly reduced in the ON vs. OFF period (P < 0.05) and this symptomatic improvement was consistent with the significant patient preference (P < 0.05) for the ON vs. OFF period determined before breaking the blind. In the unblinded portion of the study, vomiting frequency decreased significantly (P < 0.05) at 6 and 12 months. Scores for symptom severity and quality of life significantly improved (P < 0.05) at 6 and 12 months, whereas gastric emptying was only modestly accelerated. Five patients had their gastric electrical stimulation system explanted or revised because of infection or other complications.

Conclusions:

High-frequency/low-energy gastric electrical stimulation significantly decreased vomiting frequency and gastrointestinal symptoms and improved quality of life in patients with severe gastroparesis.     

Time to start putting down the knife: A systematic review of burns excision tools of randomised and non-randomised trials

Aims

Dermal preservation during acute burn excision is key to obtaining superior healing/scar outcomes, however, determining the most appropriate excision tool is an ongoing challenge. Novel tool development means the knife is no longer our only option, yet for the majority it remains the gold standard. This systematic review aims to evaluate evidence for burns excision approaches (knife/hydrosurgery/enzymatic).