In situ fabrication of cerium-incorporated hydroxyapatite/magnetite nanocomposite coatings with bone regeneration and osteosarcoma potential.

With the ultimate goal of providing a novel platform able to inhibit bacterial adhesion, biofilm formation, and anticancer properties, cerium-doped hydroxyapatite films enhanced with magnetite were developed via spin-coating. The unique aspect of the current study is the potential for creating cerium-doped hydroxyapatite/Fe3O4 coatings on a titanium support to enhance the functionality of bone implants. To assure an increase in the bioactivity of the titanium surface, alkali pretreatment was done before deposition of the apatite layer. Scanning electron microscopy (SEM) in conjunction with energy-dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD) analysis, and Fourier transform-infrared (FTIR) spectroscopy were used to evaluate coatings. Coatings demonstrated good efficacy against Staphylococcus aureus and Escherichia coli, with the latter showing the highest efficacy. In vitro bioactivity in simulated body fluid solution showed this material to be proficient for bone-like apatite formation on the implant surface. Electrochemical impedance spectroscopy was undertaken on intact coatings to examine the barrier properties of composites. We found that spin-coating at 4000 rpm could greatly increase the total resistance. After seeding with osteoblastic populations, Ce-HAP/Fe3O4 materials the adhesion and proliferation of cells. The heating capacity of the Ce-HAP/Fe3O4 film was optimal at 45 °C at 15 s at a frequency of 318 kHz. Osseointegration depends on many more parameters than hydroxyapatite production, so these coatings have significant potential for use in bone healing and bone-cancer therapy.

Titania Nanoparticle-Stimulated Ultralow Frequency Detection and High-Pass Filter Behavior of a Flexible Piezoelectric Nanogenerator: A Self-Sustaining Energy Harvester for Active Motion Tracking.

A significant driving force for the fabrication of IoT-compatible smart health gear integrated with multifunctional sensors is the growing trend in fitness and the overall wellness of the human body. In this work, we present an autonomous motion and activity-sensing device based on the efficacious nucleation of the polar ß-phase in an electroactive polymer. Representatively, we investigate the nucleating effect of TiO2 nanoparticles on weight-modulated PVDF-HFP films (PT-5, PT-10, and PT-15) and subsequently prototype a sensing device with the film that demonstrates superior ß-phase nucleation. The PT-10 film, with an optimal polar ß-phase, shows the highest remnant polarization (2Pr) and energy density of 0.36 µC/cm2 and 22.3 mJ/cm3, respectively, at 60 kV/cm. The films mimic a high pass filter at frequencies above 10 KHz with very low impedance and high ac conductivity values. The frequency-dependent impedance studies reveal an effective interfacial polarization between TiO2 nanoparticles and PVDF-HFP, explicitly observed in the low-frequency region. Consequently, the sensor fabricated with PT-10 as the sensing layer exhibits ultralow frequency detection (25 Hz) resulting from the blood flow muscle oxygenation. The device successfully senses voluntary joint movements of the human body and actively tracks a range of motions, from brisk walking to running. Additionally, through repetitive human finger-tapping motion, the nanogenerator lights up multiple light-emitting diodes in series and charges capacitors of varying magnitudes under 50 s. The real-time human motion sensing and movement tracking modalities of the sensor hold promise in the arena of smart wearables, sports biomechanics, and contact-based medical devices.

Impact of Rap-Phr system abundance on adaptation of Bacillus subtilis.

Microbes commonly display great genetic plasticity, which has allowed them to colonize all ecological niches on Earth. Bacillus subtilis is a soil-dwelling organism that can be isolated from a wide variety of environments. An interesting characteristic of this bacterium is its ability to form biofilms that display complex heterogeneity: individual, clonal cells develop diverse phenotypes in response to different environmental conditions within the biofilm. Here, we scrutinized the impact that the number and variety of the Rap-Phr family of regulators and cell-cell communication modules of B. subtilis has on genetic adaptation and evolution. We examine how the Rap family of phosphatase regulators impacts sporulation in diverse niches using a library of single and double rap-phr mutants in competition under 4 distinct growth conditions. Using specific DNA barcodes and whole-genome sequencing, population dynamics were followed, revealing the impact of individual Rap phosphatases and arising mutations on the adaptability of B. subtilis.

Pervasive prophage recombination occurs during evolution of spore-forming Bacilli.

Phages are the main source of within-species bacterial diversity and drivers of horizontal gene transfer, but we know little about the mechanisms that drive genetic diversity of these mobile genetic elements (MGEs). Recently, we showed that a sporulation selection regime promotes evolutionary changes within SPß prophage of Bacillus subtilis, leading to direct antagonistic interactions within the population. Herein, we reveal that under a sporulation selection regime, SPß recombines with low copy number phi3Ts phage DNA present within the B. subtilis population. Recombination results in a new prophage occupying a different integration site, as well as the spontaneous release of virulent phage hybrids. Analysis of Bacillus sp. strains suggests that SPß and phi3T belong to a distinct cluster of unusually large phages inserted into sporulation-related genes that are equipped with a spore-related genetic arsenal. Comparison of Bacillus sp. genomes indicates that similar diversification of SPß-like phages takes place in nature. Our work is a stepping stone toward empirical studies on phage evolution, and understanding the eco-evolutionary relationships between bacteria and their phages. By capturing the first steps of new phage evolution, we reveal striking relationship between survival strategy of bacteria and evolution of their phages.

Mutant Prevention Concentration of Ciprofloxacin against Klebsiella pneumoniae Clinical Isolates: An Ideal Prognosticator in Treating Multidrug-Resistant Strains.

BACKGROUND: Fluoroquinolone-resistant Klebsiella pneumoniae poses a therapeutic challenge when implicated in urinary tract infections, pyelonephritis, pneumonia, skin infections, osteomyelitis, and respiratory infections. The mutant prevention concentration (MPC) represents a concentration threshold above which increase of resistant mutants occurs rarely. The aim of the present study is to determine the MPC among ciprofloxacin-resistant K. pneumoniae clinical isolates. MATERIALS AND METHODS: A total of 240 clinical isolates of K. pneumoniae were collected from a tertiary care hospital. The MPCs were determined for 24 selected strains using an inoculum of 1010 CFU/ml in Müller-Hinton agar plates with serial/various concentrations (0.003-100 µg) of ciprofloxacin. In addition to the MPC, phenotypic screening for ESBL, AmpC, and carbapenemase was performed. The detection of qnr genes for 24 isolates and DNA sequencing for six isolates were performed. RESULTS: Ciprofloxacin resistance was observed in 19.6% of the K. pneumoniae clinical isolates. Among the ciprofloxacin-resistant isolates, 14 isolates showed an MPC value of more than 100 µg. The MPC ranged between 100 µg and 20 µg for ciprofloxacin-resistant isolates. ESBL producers and qnr gene-producing strains had a high MPC. 11 isolates showed the presence of either qnrB or qnrS genes. None of the samples showed the presence of the qnrA gene. CONCLUSION: From our study, we infer that ESBL producers and qnr gene-possessing strains are frequently resistant to ciprofloxacin. Estimation of the MPC in the case of multidrug-resistant isolates in the clinical setup may help in treating these drug-resistant strains.

Proanthocyanidins-Loaded Nanoparticles Enhance Dentin Degradation Resistance.

Previous studies reported that grapeseed extract (GSE), which is rich in proanthocyanidins (PAs), improves the biodegradation resistance of demineralized dentin. This study aimed to investigate the effect of a new GSE delivery strategy to demineralized dentin through loading into biodegradable polymer poly-[lactic-co-glycolic acid] (PLGA) nanoparticles on the biodegradation resistance in terms of structural stability and surface/bulk mechanical and biochemical properties with storage time in collagenase-containing solutions. GSE-loaded nanoparticles were synthetized by nanoprecipitation at PLGA/GSE (w/w) ratios of 100:75, 100:50, and 100:25 and characterized for their morphological/structural features, physicochemical characteristics, and drug loading, entrapment, and release. Nanoparticle suspensions in distilled water (12.5% w/v) were applied (1 min) to demineralized dentin specimens by simulating pulpal pressure. The nanoparticle delivery was investigated by scanning electron microscopy (SEM)/transmission electron microscopy (TEM), and the GSE release from the delivered nanoparticles was further characterized. The variations in surface and bulk mechanical properties were characterized in terms of reduced elastic-modulus, hardness, nanoindentation testing, and apparent elastic-modulus with a storage time up to 3 mo. Hydroxyproline release with exposure to collagenase up to 7 d was estimated. An etch-and-rinse dentin adhesive was applied to investigate the morphology of the resin-dentin interface after nanoparticle delivery. Treatment with the GSE-loaded nanoparticles enhanced the collagen fibril structural resistance, reflected from the TEM investigation, and improved the biomechanical and biochemical stability of demineralized dentin. Nanoparticles having PLGA/GSE of 100:75 (w/w) showed the highest cumulative GSE release and were associated with the best improvement in biodegradation resistance. TEM/SEM showed the ability of the nanoparticles to infiltrate dentinal tubules' main and lateral branches. SEM revealed the formation of a uniform hybrid layer and well-formed resin tags with the presence of numerous nanoparticles located within the dentinal tubules and/or attached to the resin tag. This study demonstrated the potential significance of delivering collagen crosslinkers loaded into biodegradable polymer nanoparticles through the dentinal tubules of demineralized dentin on the biodegradation resistance.

Chlorhexidine Nanocapsule Drug Delivery Approach to the Resin-Dentin Interface.

In this study, we are introducing a new drug-delivery approach to demineralized dentin substrates through microsized dentinal tubules in the form of drug-loaded nanocapsules. Chlorhexidine (CHX) is widely used in adhesive dentistry due to its nonspecific matrix metalloproteinase inhibitory effect and antibacterial activities. Poly(ε-caprolactone) nanocapsules (nano-PCL) loaded with CHX were fabricated by interfacial polymer deposition at PCL/CHX ratios of 125:10, 125:25, and 125:50. Unloaded nanocapsules (blank) were fabricated as control. The fabricated nanocapsules were characterized in vitro in terms of particle size, surface charges, particle recovery, encapsulation efficiency, and drug loading. Nanocapsule morphology, drug inclusion, structural properties, and crystallinity were investigated by scanning and transmission electron microscopes (SEM/TEM), energy-dispersive x-ray analysis, Fourier transform infrared spectroscopy, and x-ray diffraction. Initial screening of the antibacterial activities and the cytotoxicity of the nanocapsules were also conducted. Nanocapsules, as carried on ethanol/water solution, were delivered to demineralized dentin specimens connected to an ex vivo model setup simulating the pulpal pressure to study their infiltration, penetration depth, and retention inside the dentinal tubules by SEM/TEM. Nanocapsules were Ag labeled and delivered to demineralized dentin, followed by the application of a 2-step etch-and-rinse dentin adhesive. CHX-release profiles were characterized in vitro and ex vivo up to 25 d. Spherical nanocapsules were fabricated with a CHX core coated with a thin PCL shell. The blank nanocapsules exhibited the largest z-average diameter with negatively charged ζ-potential. With CHX incorporation, the nanocapsule size was decreased with a positive shift in ζ-potential. Nano-PCL/CHX at 125:50 showed the highest drug loading, antibacterial effect, and CHX release both in vitro and ex vivo. SEM and TEM revealed the deep penetration and retention of the CHX-loaded nanocapsules inside dentinal tubules and their ability to be gradually degraded to release CHX in vitro and ex vivo. Ag-labeled nanocapsules revealed the close association and even distribution of nanocapsules throughout the resin tag structure. This study demonstrated the potential of introducing this novel drug-delivery approach to demineralized dentin substrates and the resin-dentin interface with nanosized CHX-loaded nanocapsules through the microsized dentinal tubules.

Intralesional Sclerotherapy - A Novel Approach for The Treatment of Intraoral Haemangiomas.

In infancy and childhood haemangiomas are the most common neoplasms in head and neck region with an occurrence of about 60%. Approximately 40%-50% of all haemangiomas resolve incompletely, leaving permanent changes in the skin, such as telangiectases, epidermal atrophy, hypopigmentation or redundant skin with fibro-fatty residue but a few stubborn, problematic haemangiomas may result in serious disfigurement and dysfunction, and even become life-threatening. Most haemangiomas are managed by conservative methods that include corticosteroids (either systemic or local injection), sclerotherapy, interferon-alpha, laser therapy, embolization, cryotherapy, and radiation. Due to risk of haemorrhaging, surgical removal for small vascular lesions is not considered and it is more invasive than sclerotherapy. This case report presents the efficacy of intralesional sclerotherapy for the management of haemangiomas on dorsum and lateral border of tongue.

Synthesis and antihistaminic activity of 3H-benzo [4,5] thieno [2,3-d][1,2,3] triazin-4-ones.

In the present study the antihistaminic activity of tricyclic benzothieno 1,2,3-triazine derivatives namely CP-3 (3-(phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one), CP-5 (3-(3-methyl phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) and CP-8 (3-(4-chloro phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) were evaluated using in vitro (isolated guinea pig ileum) and in vivo (bronchodilator activity in guinea pigs) models and the sedative potential of the test compounds were evaluated using actophotometer in mice. In in vitro antihistaminic study, the CP-3, CP-5, CP-8 and chlorpheniramine maleate (CPM) have shown a rightward shift in concentration response curve (CRC) of histamine with a change in EC50 values of histamine in all the four tissue preparations. The slope obtained in the schild plot indicated that CP-5, CP-8 and CPM were competitive in nature for H1-receptors. However, CP-3 has shown non-competitive antagonism. In in vivo antihistaminic study, the CP-3, CP-5, CP-8 and CPM have shown mean increase in exposition time against histamine challenge compared to control group (p < 0.001). All the test drugs (10 mg/kg) and CPM (2 mg/kg) have offered a significant (p < 0.001) protection against preconvulsive dyspnoea (PCD) compared to control. In conclusion, all the test drugs have shown very good antihistaminic activity and the test drugs have very little sedative action compared to CPM.