Synthesis,biological evaluation and in silico molecular docking of novel 1-hydroxy-naphthyl substituted heterocycles

The versatile precursor 2-acetyl-4-allyl-1-hydroxy naphthalene was synthesized efficiently via Claisen rearrangement 2-acetyl-1-allyloxynaphthalene. The Claisen-Schmidt condensation of latter precursor afforded the corresponding chalcones which were exploited to synthesize a series of potential heterocycles such as pyrazoline, isoxazoline, benzocoumarin and benzoflavone. The synthesized products showed potent antioxidant and antimicrobial activities. Chalcone 3c, naphthyl pyrazoline 6b and hydroxycoumarin 13 exhibited the highest activity as antioxidants. Their binding mode showed specialized recognition of hydroxycoumarin 13 with the triad key amino acids at the active site of the oxidoreductase enzyme (PDB code 1DXO). 1-Hydroxynaphth-2-yl pyrazoline (6b) revealed the highest efficacy against both Gram positive and negative bacterial species. In silico molecular docking of pyrazoline 6b endorsed its proper binding at the active site of the 2EX6 enzyme which explains its potent antibacterial activity in comparison with standard ampicillin.     

'Smart' delivery systems for biomolecular therapeutics

OBJECTIVE: There is a strong need for drug delivery systems that can deliver biological signals from biomaterials and tissue engineering scaffolds, and a particular need for new delivery systems that can efficiently deliver biomolecules to intracellular targets. Viruses and pathogens have evolved potent molecular machinery that sense the lowered pH gradient of the endosomal compartment and become activated to destabilize the endosomal membrane, thereby enhancing protein or DNA transport to the cytoplasmic compartment. A key feature of many of these biological delivery systems is that they are reversible, so that the delivery systems are not directly toxic. These delivery systems have the ability to change their structural and functional properties and thus display remarkable 'smart' material properties. The objective of this presentation is to review the initial development of smart polymeric carriers that mimic these biological delivery systems and combine similar pH-sensitive, membrane-destabilizing activity for the delivery of therapeutic biomolecules. DESIGN: We have developed new 'smart' polymeric carriers to more effectively deliver and broaden the available types of biomolecular therapeutics. The polymers are hydrophilic and stealth-like at physiological pH, but become membrane-destabilizing after uptake into the endosomal compartment where they enhance the release of therapeutic cargo into the cytoplasm. They can be designed to provide a range of pH profiles and membrane-destabilizing activities, allowing their molecular properties to be matched to specific drugs and loading ranges. A versatile set of linker chemistries is available to provide degradable conjugation sites for proteins, nucleic acids, and/or targeting moieties. RESULTS: The physical properties of several pH-responsive polymers were examined. The activity and pH profile can be manipulated by controlling the length of hydrophobic alkyl segments. The delivery of poly(propyl acrylic acid) (PPAA)-containing lipoplexes significantly enhanced wound healing through the interconnected effects of altered extracellular matrix organization and greater vascularization. PPAA has also been shown to enhance cytoplasmic delivery of a model protein therapeutic. Polymeric carriers displaying pH-sensitive, membrane-destabilizing activity were also examined. The pH profile is controlled by the choice of the alkylacrylic acid monomer and by the ratio of the carboxylate-containing alkylacrylic acid monomer to alkylacrylate monomer. The membrane destabilizing activity is controlled by the lengths of the alkyl segment on the alkylacrylic acid monomer and the alkylacrylate monomer, as well as by their ratio in the final polymer chains. CONCLUSION: The molecular mechanisms that proteins use to sense and destabilize provide interesting paradigms for the development of new polymeric delivery systems that mimic biological strategies for promoting the intracellular delivery of biomolecular drugs. The key feature of these polymers is their ability to directly enhance the intracellular delivery of proteins and DNA, by destabilizing biological membranes in response to vesicular compartment pH changes. The ability to deliver a wide variety of protein and nucleic acid drugs to intracellular compartments from tissue engineering and regenerative scaffolds could greatly enhance control of important processes such as inflammation, angiogenesis, and biomineralization.     

Abductive Learning Ensembles for Hand Shape Identification

A novel method is presented for hand shape identification based on abductive machine learning. We developed several models and investigated their performance on raw hand shape data for 20 and 40 participants in the form of three different categories of geometric measurements: twelve finger features, two palm features, and three whole hand features. Performance was compared when using each category of features separately and when combining them together. Moreover, we describe two novel and more effective approaches using an ensemble of three abductive networks combined at either the score level or the decision level. The effect of doubling the number of participants from 20 to 40 was studied as well. The ensemble approach achieved overall identification accuracies of 100 and 98.3333 % for the 20-participant and 40-participant datasets, respectively. This compares favorably with other learning approaches tried on the same datasets, including decision trees, support vector machines, and rule-based classifiers.     

Evaluation of scars in children after treatment with low-level laser

Burn scars are known for their tendency to worsen with hypertrophy and contracture, causing esthetic and functional problems. The objective is to analyze the effectiveness of low-level laser therapy on post-burn hypertrophic scar tissue in children. A randomized controlled study included 15 children, ranging from 2 to 10 years of age, presented with post-burn hypertrophic scars. They received He-Ne laser and topical treatment. Each scar was divided into two halves. One half was treated with laser therapy and topical treatment (study area), and the other half was treated with topical treatment only (control area). The children were evaluated before, and after 3 months of the study by Vancouver Scar Scale (VSS), ultrasonography, and laser Doppler perfusion imaging. Significant improvement was reported in the studied area, compared to the control area for patients with P values (P =?0.003) and (P =?0.005), for VSS and U/S scores, respectively. No differences were detected for blood perfusion of the scar between both areas (P?=?0.73). In addition, no adverse effects were reported. Photobiomodulation (PBM) is an efficient and safe therapeutic modality for post-burn hypertrophic scars in children, with no side effects, and should be considered a part of combination therapy for better results.     

Dega osteotomy for the management of developmental dysplasia of the hip in children aged 2–8?years: results of 58 consecutive osteotomies after 13–25?years of follow-up

PurposeDevelopmental dysplasia of the hip (DDH) is a term used to cover a broad spectrum of anomalies ranging from mild dysplasia to high-riding dislocations. We report the management of DDH in children using the Dega osteotomy and their long-term follow-up.MethodsFifty-eight hips from 48 children younger than 8 years treated using the Dega osteotomy between January 1988 and October 2000 were included in this multcenter study. Both prospective (41 hips) and retrospective (17 hips) cases were included, and follow-up was for a minimum of 13 years. Radiographs were made preoperatively, immediately postoperatively, after 6 weeks or at removal of the spica cast if any, at 6-month intervals and/or as indicated for 3 years postoperatively and then on annual basis until the last follow-up. A single-cut computed tomographic scan was performed for all prospective patients. Special attention was paid to the predictive measures of hip arthrosis and the survival of the hip after Dega osteotomy. ResultsThe final clinical outcome was favorable in 44 hips (75.9 %). Eleven hips needed a second surgery (acetabuloplasty and/or arthroplasty) during the follow-up period.Conclusions In our pediatric patient population the Dega osteotomy proved to be an adequate measure for the management of this complex condition. The worst complication was avascular necrosis, and all of the affected hips ended with failure (pain, another surgery, or both).