Effects of nasal continuous positive-airway pressure on nutritive swallowing in lambs

Current knowledge suggests that, to be successful, oral feeding in preterm infants should be initiated as soon as possible, often at an age where immature respiration still requires ventilatory support in the form of nasal continuous positive airway pressure (nCPAP). While some neonatologist teams claim great success with initiation of oral feeding in immature infants with nCPAP, others strictly wait for this ventilatory support to be no longer necessary before any attempt at oral feeding, fearing laryngeal penetration and tracheal aspiration. Therefore, the aim of the present study was to provide a first assessment of the effect of various levels of nCPAP on bottle-feeding in a neonatal ovine model, including feeding safety, feeding efficiency, and nutritive swallowing-breathing coordination. Eight lambs born at term were surgically instrumented 48 h after birth to collect recordings of electrical activity of laryngeal constrictor muscle, electrocardiography, and arterial blood gases. Two days after surgery, lambs were bottle-fed under five randomized nCPAP conditions, including without any nCPAP or nasal mask and nCPAP of 0, 4, 7, and 10 cmH(2)O. Results revealed that application of nCPAP in the full-term lamb had no deleterious effect on feeding safety and efficiency or on nutritive swallowing-breathing coordination. The present study provides a first and unique insight on the effect of nCPAP on oral feeding, demonstrating its safety in newborn lambs born at term. These results open the way for further research in preterm lambs to better mimic the problems encountered in neonatology.     

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Background

Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).

Methods

Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.

Results

The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).

Conclusion

We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.

Trial registration

ClinicalTrials.gov: NCT00149591.     

Quick identification of kuraridin, a noncytotoxic anti-MRSA (methicillin-resistant Staphylococcus aureus) agent from Sophora flavescens using high-speed counter-current chromatography

Bacterial resistance to antibiotics has become a serious problem of public health that concerns almost all currently used antibacterial agents and that manifests in all fields of their application. To find more antibacterial agents from natural resources is all the time considered as an important strategy. Sophora flavescens is a popularly used antibacterial herb in Chinese Medicine, from which prenylated flavones were reported as the antibacterial ingredients but with a major concern of toxicity. In our screening on the antibacterial activities of various chemicals of this herb, 18 fractions were obtained from 8 g of 50% ethanol extract on a preparative high-speed counter-current chromatography (HSCCC, 1000 ml). The system of n-hexane/ethyl acetate/methanol/water (1:1:1:1) was used as the two-phase separation solvent. A chalcone named kuraridin was isolated from the best anti-MRSA fraction, together with sophoraflavanone G, a known active ingredient of S. flavescens. Their structures were elucidated by analysis of the NMR spectra. Both compounds exhibited significant anti-MRSA effects, compared to baicalein that is a well known anti-MRSA natural product. More important, kuraridin showed no toxicity on human peripheral blood mononuclear cells (PBMC) at the concentration up to 64 μg/ml while sophoraflavanone G inhibited over 50% of cellular activity at 4 μg/ml or higher concentration. These data suggested that opening of ring A of the prenylated flavones might decrease the toxicity and remain the anti-MRSA effect, from a viewpoint of structure-activity relationship.     

Mutations affecting the oligomerization interface of G-protein-coupled receptors revealed by a novel de novo protein design framework

Specific functional and pharmacological properties have recently been ascribed to G-protein-coupled receptor (GPCR) dimers/oligomers. Because the association of two identical or two distinct GPCR monomers seems to be required to elicit receptor function, it is necessary to understand the exact nature of this interaction. We present here a novel method for de novo protein design and its application to the prediction of mutations that can stabilize or destabilize a GPCR dimer while maintaining the monomer's native fold. To test the efficacy of this new method, the dimer of the single-spanned transmembrane domain of glycophorin A was used as a model system. Experimental data from mutagenesis of the helix-helix interface are compared with computational predictions at that interface, and the model's results are found to be consistent with the experimental findings. A flexible template was developed for the rhodopsin homodimer at atomic resolution and used to predict sets of three and five mutations. The results are found to be consistent across eight case studies, with favored mutations at each position. Mutation sets predicted to be the most disruptive at the dimerization interface are found to be less specific to the flexible template than sets predicted to be less disruptive.     

Recent knowledge and innovations related to hexofuranosides: structure, synthesis and applications

Hexofuranosides are widely spread in nature, and notably in numerous pathogenic microorganisms. This particular five-membered ring for hexosides leads to novel biological properties and, as usual in glycochemistry, to completely different reactivity and selectivity. Far from being exhaustive, this review will first focus on the structure of the oligosaccharidic part of hexofuranosyl conjugates found in natural sources. Original syntheses will then be presented, stressing more particularly on the development of chemical and chemo-enzymatic tools for the access to 1,2-trans or 1,2-cis linkages. Finally, innovative applications related to biological, chemical and physicochemical fields for both natural and synthetic hexofuranosyl compounds will be described.     

A three-pressure-sensor (3PS) system for monitoring ankle supination torque during sport motions

This study presented a three-pressure-sensor (3PS) system for monitoring ankle supination torque during sport motions. Five male subjects wore a pair of cloth sport shoes and performed 10 trials of walking, running, cutting, vertical jump-landing and stepping-down motions in a random sequence. A pair of pressure insoles (Novel Pedar model W, Germany) was inserted in the shoes for the measurement of plantar pressure at 100Hz. The ankle joint torque was calculated by a standard lower extremity inverse dynamic calculation procedure with the data obtained by a motion capture system (VICON, UK) and a force plate (AMTI, USA), and was presented in a supination/pronation plane with an oblique axis of rotation at the ankle joint. Stepwise linear regression analysis suggested that pressure data at three locations beneath the foot were essential for reconstructing the ankle supination torque. Another group of five male subjects participated in a validation test with the same procedure, but with the pressure insoles replaced by the 3PS system. Estimated ankle supination torque was calculated from the equation developed by the regression analysis. Results suggested that the correlation between the standard and estimated data was high (R=0.938). The overall root mean square error was 6.91Nm, which was about 6% of the peak values recorded in the five sport motions (113Nm). With the good estimation accuracy, tiny size and inexpensive cost, the 3PS system is readily available to be implanted in sport shoe for the estimation and monitoring of ankle supination torque during dynamic sport motions.     

Tissue distribution of human AKR1C3 and rat homolog in the adult genitourinary system

Human aldo-keto reductase (AKR) 1C3 (type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase) catalyzes androgen, estrogen, and prostaglandin metabolism. AKR1C3 is therefore implicated in regulating ligand access to the androgen receptor, estrogen receptor, and peroxisome proliferator activating receptor gamma in hormone target tissues. Recent reports on close relationships between ARK1C3 and various cancers including breast and prostate cancers implicate the involvement of AKR1C3 in cancer development or progression. We previously described the characterization of an isoform-specific monoclonal antibody against AKR1C3 that does not cross-react with related, >86% sequence identity, human AKR1C1, AKR1C2, or AKR1C4, human aldehyde reductase AKR1A1, or rat 3alpha-hydroxysteroid dehydrogenase (AKR1C9). In this study, a clone of murine monoclonal antibody raised against AKR1C3 was identified and characterized for its recognition of rat homolog. Tissue distribution of human AKR1C3 and its rat homolog in adult genitourinary systems including kidney, bladder, prostate, and testis was studied by IHC. A strong immunoreactivity was detected not only in classically hormone-associated tissues such as prostate and testis but also in non-hormone-associated tissues such as kidney and bladder in humans and rats. The distribution of these two enzymes was comparable but not identical between the two species. These features warrant future studies of AKR1C3 in both hormone- and non-hormone-associated tissues and identification of the rodent homolog for establishing animal models.     

Value of endoscopic retrograde cholangiopancreatography-guided brushings in preoperative assessment of pancreaticobiliary strictures: what's new?

Brush cytology plays a prominent role in confirming the presence of extrahepatic biliary tract malignancy. However, its value is limited by its relatively low and widely variable sensitivity values. Various factors seem to influence the accuracy of cytologic diagnosis and are attributed to sampling, technical and interpretation errors. Ancillary methods, such as immunocytochemistry, flow cytometry, image analysis, fluorescence in situ hybridization (FISH) and the newly discovered method of global analysis of gene expression are helpful in resolving cases with inconclusive cytology and are vigorously investigated for their value in assessing the expression of novel tumor markers for the diagnosis and prognosis of pancreatic and bile duct carcinomas. However, their routine use in clinical practice remains in doubt. To increase the sensitivity of brush cytology and strengthen its role in the preoperative assessment of patients with pancreaticobiliary malignancies, the following are of the utmost importance: improvement of current sampling and cytopreparation techniques, introduction of a uniform system for reporting epithelial abnormalities based on strict and clearly distinct morphologic criteria for each pathologic entity and incorporation of experience and knowledge derived from standard cytologic methods and novel diagnostic technologies in clinical practice without compromising the high specificity associated with brush cytology.