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131.
The aim of the present study was to evaluate the antimicrobial activity of two synbiotic combinations, Lactobacillus fermentum with short-chain fructooligosaccharides (FOS-LF) and Bifidobacterium longum with isomaltooligosaccharides (IMO-BL), against enterohaemorrhagic Escherichia coli O157:H7 and enteropathogenic E. coli O86. Antimicrobial activity was determined (1) by co-culturing the synbiotics and pathogens in batch cultures, and (2) with the three-stage continuous culture system (gut model), inoculated with faecal slurry from an elderly donor. In the co-culture experiments, IMO-BL was significantly inhibitory to both E. coli strains, while FOS-LF was slightly inhibitory or not inhibitory. Factors other than acid production appeared to play a role in the inhibition. In the gut models, both synbiotics effectively inhibited E. coli O157 in the first vessel, but not in vessels 2 and 3. E. coli O86 was not significantly inhibited.  相似文献   
132.
Farnesyltransferase (FTase) is one of the prenyltransferase family enzymes that catalyse the transfer of 15-membered isoprenoid (farnesyl) moiety to the cysteine of CAAX motif-containing proteins including Rho and Ras family of G proteins. Inhibitors of FTase act as drugs for cancer, malaria, progeria and other diseases. In the present investigation, we have developed two structure-based pharmacophore models from protein–ligand complex (3E33 and 3E37) obtained from the protein data bank. Molecular dynamics (MD) simulations were performed on the complexes, and different conformers of the same complex were generated. These conformers were undergone protein–ligand interaction fingerprint (PLIF) analysis, and the fingerprint bits have been used for structure-based pharmacophore model development. The PLIF results showed that Lys164, Tyr166, TrpB106 and TyrB361 are the major interacting residues in both the complexes. The RMSD and RMSF analyses on the MD-simulated systems showed that the absence of FPP in the complex 3E37 has significant effect in the conformational changes of the ligands. During this conformational change, some interactions between the protein and the ligands are lost, but regained after some simulations (after 2 ns). The structure-based pharmacophore models showed that the hydrophobic and acceptor contours are predominantly present in the models. The pharmacophore models were validated using reference compounds, which significantly identified as HITs with smaller RMSD values. The developed structure-based pharmacophore models are significant, and the methodology used in this study is novel from the existing methods (the original X-ray crystallographic coordination of the ligands is used for the model building). In our study, along with the original coordination of the ligand, different conformers of the same complex (protein–ligand) are used. It concluded that the developed methodology is significant for the virtual screening of novel molecules on different targets.  相似文献   
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Background

Laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding all lead to substantial weight loss in obese patients. Long-term weight loss can be highly variable beyond 1-year postsurgery. This study examines and compares the frequency distribution of weight loss and lack of treatment effect rates after laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding.

Methods

A total of 1,331 consecutive patients at a single academic institution were reviewed from a prospectively collected database. Preoperative data collected included demographics, body mass index, and percent excess weight loss. Postoperative BMI and %EWL were collected at 12, 24, and 36 months. Percent excess weight loss was analyzed by the percentiles of excess weight lost, and the distribution of percent excess weight loss was evaluated in 10% increments. Lack of a successful treatment effect was defined as <25% excess weight loss.

Results

Of the 1,331 patients, 72.4% (963) underwent laparoscopic Roux-en-Y gastric bypass, 18.3% (243) laparoscopic sleeve gastrectomy, and 9.4%(125) laparoscopic adjustable gastric banding. Mean percent excess weight loss was greatest for laparoscopic Roux-en-Y gastric bypass, followed by laparoscopic sleeve gastrectomy, and then by laparoscopic adjustable gastric banding at every time point: at 2 years mean percent excess weight loss was 77.9± 24.4 for laparoscopic Roux-en-Y gastric bypass, 50.8 ± 25.8 for laparoscopic sleeve gastrectomy, and 40.8± 25.9 for laparoscopic adjustable gastric banding (P < .0001). The rates of a successful treatment effect s for laparoscopic Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy, and laparoscopic adjustable gastric banding were 0.9%, 5.2%, and 24.3% at 1 year; 0.3%, 11.1%, and 26.0% at 2 years; and 1.0%, 25.3%, and 30.2% at 3 years. At 1 year, the odds ratio of lack of a successful treatment effect of laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass was 6.305 (2.125–19.08; P?=?.0004), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass was 36.552 (15.64–95.71; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy was 5.791 (2.519–14.599; P < .0001). At 2 years, the odds ratio for laparoscopic sleeve gastrectomy versus laparoscopic Roux-en-Y gastric bypass increased to 70.7 (9.4–531.7; P < .0001), the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic Roux-en-Y gastric bypass increased to 128.1 (16.8–974.3; P < .0001), and the odds ratio for laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy decreased to 1.8 (0.9–3.6; P?=?.09).

Conclusion

This study emphasizes the existing variability in weight loss across bariatric procedures as well as in the lack of a treatment effect for each procedure. Although laparoscopic adjustable gastric banding has the greatest rate of a lack of a successful treatment effect, the rate remained stable over 3 years postoperatively. Laparoscopic sleeve gastrectomy showed a doubling in the rate of a lack of a successful treatment effect every year reaching 25% at year 3. The rates for lack of a successful treatment effect for laparoscopic Roux-en-Y gastric bypass remained stable at about 1% for the first 3 years postoperatively.  相似文献   
138.

Objective

Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.

Methods

From 2005 to 2017, 593 neonates in the Congenital Heart Surgeons' Society Critical Left Heart Obstruction cohort underwent a Norwood procedure. Median follow-up was 3.7 years. Multivariable parametric models, including a modulated renewal analysis, were performed.

Results

Of the 593 neonates, 146 (25%) underwent 218 reinterventions for arch obstruction after the Norwood procedure: catheter-based (n = 168) or surgical (n = 50) at a median age of 4.3 months (quartile 1-quartile 3, 2.6-5.7). Interdigitation of the distal aortic anastomosis was protective against arch reintervention. Development of ≥ moderate tricuspid valve regurgitation and right ventricular dysfunction at any point was associated with arch reintervention. Nonsignificant variables for arch reintervention included shunt type and preoperative aortic measurements. Surgical arch reintervention was protective against arch reintervention, but transcatheter reintervention was associated with increased reintervention. Arch reintervention was not associated with increased mortality. There was wide institutional variation in incidence of arch reintervention (range, 0-40 reinterventions per 100 years patient follow-up) and in preintervention gradient (range, 0-64 mm Hg).

Conclusions

Interdigitation of the distal aortic anastomosis during the Norwood procedure decreased the risk of arch reintervention. Surgical arch reintervention is more definitive than transcatheter. Arch reintervention after the Norwood procedure is not associated with increased mortality. Serial surveillance for arch obstruction, integrated with changes in right ventricular function and tricuspid valve regurgitation, is recommended after the Norwood procedure to improve outcomes.  相似文献   
139.

Background

Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.

Materials and methods

Initially, EGCG was assayed on the rabbit corneal epithelial cell line RCE1(5T5) to establish the best testing conditions, and to avoid unwanted outcomes in the experimental animals. Then, we studied its effects on cell proliferation, cell cycle progression and cell differentiation. Afterwards, we instilled EGCG in experimental grade II corneal alkali burns in mice, three times a day up to 21 days, and evaluated by slit lamp examination and histological sections of corneal epithelial, corneal endothelial and stromal edema, as well as the presence of inflammatory cells and neovascularization.

Results

EGCG reduced cell growth and led to a decline in the proportion of proliferative cells in a concentration dependent manner. At 10 μM, EGCG promoted cell differentiation, an effect not related with apoptosis or cytotoxicity. When 10 μM EGCG was instilled in corneal alkali burns in mice three times a day up to 21 days, EGCG significantly reduced corneal opacity and neovascularization. The improved clinical appearance of the cornea was associated to a controlled epithelial growth; epithelial morphology was similar to that observed in normal epithelium and contrasted with the hyperproliferative, desquamating epithelium observed in control burn wounds. EGCG reduced corneal, stromal and endothelial edema, and wound inflammation.

Conclusion

This work constitutes the first evidence for the use of EGCG in the acute phase of a corneal alkali burn, representing a possible novel alternative to improve patient outcomes as an add-on therapy.  相似文献   
140.
BackgroundThe measurement of health-related quality of life (HRQoL) provides information about the perceived burden of the health condition and treatments from a lived experience. The Brisbane Burn Scar Impact Profile (caregiver report for young children, BBSIP0–8), developed in 2013, is a proxy-report measure of burn scar-specific HRQoL. The aim of this study was to report its psychometric properties in line with an evaluative purpose.MethodsCaregivers of children up to 8 years of age at risk of burn scarring were recruited into a prospective, longitudinal cohort study. Caregivers completed the BBSIP0–8, Pediatric Quality of Life Inventory and Patient Observer Scar Assessment Scale at baseline (approximately ≥85% of the total body surface area re-epithelialised), 1–2 weeks after baseline and 1-month after baseline. Psychometric properties measured included internal consistency, test–retest reliability, validity and responsiveness.ResultsEighty-six caregivers of mostly male children (55%), of a median age (IQR) of 1 year, 10 months (2 years, 1 month) and total body surface area burn of 1.5% (3.0%) were recruited. Over one third of participants were grafted and 15% had contractures or skin tightness at baseline. Internal consistency of ten item groups ranged from 0.73 to 0.96. Hypothesised correlations of changes in the BBSIP0–8 items with changes in criterion measures supported longitudinal validity (ρ ranging from ?0.73 to 0.68). The majority of item groups had acceptable reproducibility (ICC = 0.65–0.83). The responsiveness of five item groups was supported (AUC = 0.71–0.90).ConclusionThe psychometric properties tested support the use of the BBSIP0–8 as an evaluative measure of burn scar-related health-related quality of life for children aged below eight years in the early post-acute period of rehabilitation. Further investigation at longer time period after burn injury is indicated.  相似文献   
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