Localized deferoxamine injection augments vascularity and improves bony union in pathologic fracture healing after radiotherapy

BackgroundMedically based efforts and alternative treatment strategies to prevent or remediate the corrosive effects of radiotherapy on pathologic fracture healing have failed to produce clear and convincing evidence of success. Establishing an effective pharmacologic option to prevent or treat the development of non-unions in this setting could have immense therapeutic potential. Experimental studies have shown that deferoxamine (DFO), an iron-chelating agent, bolsters vascularity and subsequently enhances normal fracture healing when injected locally into a fracture callus in long bone animal models. Since radiotherapy is known to impede angiogenesis, we hypothesized that the pharmacologic addition of DFO would serve to mitigate the effects of radiotherapy on new vessel formation in vitro and in vivo.Materials and MethodsIn vitro investigation of angiogenesis was conducted utilizing HUVEC cells in Matrigel. Endothelial tubule formation assays were divided into four groups: Control, Radiated, Radiated + Low-Dose DFO and Radiated + High-Dose DFO. Tubule formation was quantified microscopically and video recorded for the four groups simultaneously during the experiment. In vivo, three groups of Sprague–Dawley rats underwent external fixator placement and fracture osteotomy of the left mandible. Two groups received pre-operative fractionated radiotherapy, and one of these groups was treated with DFO after fracture repair. After 40 days, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics.ResultsIn vitro, endothelial tubule formation assays demonstrated that DFO mitigated the deleterious effects of radiation on angiogenesis. Further, high-dose DFO cultures appeared to organize within 2 h of incubation and achieved a robust network that was visibly superior to all other experimental groups in an accelerated fashion. In vivo, animals subjected to a human equivalent dose of radiotherapy (HEDR) and left mandibular fracture demonstrated quantifiably diminished μCT metrics of vascular density, as well as a 75% incidence of associated non-unions. The addition of DFO in this setting markedly improved vascularity as demonstrated with 3D angiographic modeling. In addition, we observed an increased incidence of bony unions in the DFO treated group when compared to radiated fractures without treatment (67% vs. 25% respectively).ConclusionOur data suggest that selectively targeting angiogenesis with localized DFO injections is sufficient to remediate the associated severe vascular diminution resulting from a HEDR. Perhaps the most consequential and clinically relevant finding was the ability to reduce the incidence of non-unions in a model where fracture healing was not routinely observed.     

Performance evaluation of a low-cost,novel vanadium nitride xerogel (VNXG) as a platinum-free electrocatalyst for dye-sensitized solar cells

A vanadium nitride xerogel (VNXG) was synthesised by a simple and effective method of ammonialising a vanadium pentoxide xerogel at a higher temperature. Xerogel-structured materials possess salient features such as high surface area, tunable porosity and pore size that result in enhancing the catalytic activity by a fast electron-transport pathway and increase electrolyte diffusion channels. Metal nitrides are reported as promising alternate low-cost counter electrodes to replace the conventional and expensive platinum (Pt) counter electrode. Though few studies are reported on aerogel-based CEs for DSSCs, the present work is the first attempt to synthesize and evaluate the performance of xerogel-structured metal nitrides as counter electrode materials for dye-sensitized solar cells. The synthesized material was well characterized for its structural and morphological characteristics and chemical constituents by photoelectron spectroscopy. Finally, the VNXG was tested for its electrocatalytic performance as a choice of counter electrodes for dye-sensitized solar cells (DSSCs). The photo-current studies were performed under standard 1 SUN, class AAA-simulated illumination with AM1.5G. The consolidated results revealed that the vanadium nitride xerogel exhibited good photocatalytic activity and low charge transfer resistance. This identified it as a promising low-cost counter electrode (CE) material for dye-sensitized solar cells. The photo-current conversion efficiency of the vanadium nitride xerogel CE-based DSSC reached 5.94% comparable to that of the conventional thermal decomposed Pt CE-based DSSC, 7.38% with the same iodide/triiodide electrolyte system. Moreover, the 28 days stability study of VNXG CE DSSCs provided an appreciably stable performance with 37% decrement in the PCE under the same test condition.

A vanadium nitride xerogel (VNXG) was synthesised by a simple and effective method of ammonialising a vanadium pentoxide xerogel at a higher temperature. The electrochemical and photo-current studies were performed towards a counter electrode for DSSC.     

Magnetically separable Zn1−xCo0.5xMg0.5xFe2O4 ferrites: stable and efficient sunlight-driven photocatalyst for environmental remediation

Nanomaterials have recently gained significant interest as they are believed to offer an outstanding prospect for use in environmental remediation. Among many possible candidates, due to their useful properties including magnetic nature, wide surface area, and high absorptivity, ferrite materials hold tremendous appeal, allowing them to be used for multifaceted applications. In the present study, using a sol–gel auto combustion process, a magnetically separable Zn_1−xCo_0.5xMg_0.5xFe₂O₄ (x = 0.0, 0.25, 0.50, 0.75, 1.0) ferrite with superior photocatalytic activity for dye degradation was manufactured. Rietveld refinement and FTIR studies confirm that a single-phase cubic spinel system was built for all samples with crystallite sizes of 34–57 nm. VSM has determined the magnetic properties of the samples at room temperature. With the introduction of Mg²⁺ and Co²⁺ in the Zn ferrites, a transformation from the soft superparamagnetic activity to the hard ferromagnetic character was reported. Considering the band structure in the visible region, the photocatalytic activities of the Zn_1−xCo_0.5xMg_0.5xFe₂O₄ ferrites for the degradation of the MB dye under natural sunlight were investigated. Zn_0.25Co_0.375Mg_0.375Fe₂O₄ showed an efficiency of degradation of 99.23% for MB dye with a quick 40 min irradiation period with high reusability of up to four cycles.

Nanomaterials have recently gained significant interest as they are believed to offer an outstanding prospect for use in environmental remediation.     

Digital assessment and quantification of pelvic organ prolapse (DPOP-Q): a randomised cross-over diagnostic agreement trial

Introduction

Pelvic Organ Prolapse Quantification (POP-Q) system, measured in centimetres using a ruler (e.g. POPstix®), is recommended to quantify prolapse severity. POPstix® are costly (US $1/ruler). Home-made devices are used instead, but these have not been shown to be reproducible.

Hypothesis

Digitally assessed POP-Q (DPOP-Q) is as reliable, reproducible and acceptable as POP-Q assessed using POPstix®.

Methods

In this randomised crossover diagnostic agreement trial, each assessor measured the index finger of their dominant hand using a ruler. At visit one, patients were randomised to either POPstix® POP-Q assessment in a modified lithotomy position or DPOP-Q in both modified a lithotomy and a standing position. After the first clinician conducted this assessment, a second blinded clinician then carried out the remaining assessment on the same patient. For each examination, duration was recorded, along with a patient-completed discomfort score. Twenty-five women were invited for visit two, at which DPOP-Q was recorded by the same clinician who undertook DPOP-Q at the first visit. This allowed evaluation of inter- and intraobserver agreement together with examination acceptability.

Results

One hundred and nine women were recruited [median age 55 years, parity 2, body mass index (BMI) 27.1]. Of the 25 patients invited, 23 returned for visit two. DPOP-Q had high interobserver reliability [κ?=?0.94, 95 % confidence interval (CI) 0.878–0.996] and intraobserver reliability (α?=?0.96) with POPstix®. DPOP-Q was significantly quicker (p?=?0.02) and less uncomfortable (p?<?0.01) than POPstix® POP-Q.

Conclusion

DPOP-Q is reliable, acceptable and cost effective.

     

Nuclear gyrB encodes a functional subunit of the Plasmodium falciparum gyrase that is involved in apicoplast DNA replication

The DNA replication machinery of the Plasmodium falciparum apicoplast is a validated drug target. Nuclear-encoded gyrase subunits are predicted to play a critical role in maintaining DNA topology during the D-loop/bi-directional ori replication process of the parasite. We show the presence of P. falciparum gyrase subunits in parasite lysates by using antibodies generated against recombinant gyrase A and B. The ATPase activity of PfGyrB was inhibited by novobiocin that also caused parasite death in culture. Reduction of apicoplast/nuclear DNA ratio in the presence of novobiocin indicated that the drug targets apicoplast DNA replication. Molecular modeling of gyrase A and B subunits revealed extensive fold conservation with the Escherichia coli counterparts as well as the presence of a long disordered loop adjacent to the ATPase domain of PfGyrB. Our results have implications for development of PfGyrB as a drug target against malaria.     

Purification and characterisation of a novel antistaphylococcal peptide (ASP-1) from Bacillus sp. URID 12.1

A strong antistaphylococcal peptide (ASP-1) from Bacillus subtilis URID 12.1 strain that is active against cefoxitin- and methicillin-resistant Staphylococcus aureus clinical isolates was purified to homogeneity by solvent extraction, silica gel-based adsorption chromatography and reversed-phase high-performance liquid chromatography. The peptide sequence of ASP-1 as determined by MALDI-TOF/MS and ESI-FTICR-MS was acetylated Phe-Thr-Ala-Val-Dhb-Phe-Ile/Leu. The peptide was further analysed by alkaline hydrolysis, ESI-Q-TOF-MS and an ion mobility assay, which detected the presence of a lactone ring in the intact peptide and a cyclic nature, subsequently revealing the linearised peptide sequence as acPhe-Leu-Phe-Thr-Val-Ala-Dhb. Based on the molecular mass (804.5 Da), peptide sequence and amino acid composition, ASP-1 was identified as a lactone ring-containing peptide similar to TL-119, a poorly studied cyclic depsipeptide. Circular dichroism spectroscopy revealed its predominantly random structure in aqueous solution and its β-sheet conformation in methanol. Minimum inhibitory concentrations (MICs) of the purified peptide against S. aureus and methicillin-resistant S. aureus (MRSA) ranged from 2?µg/mL to 64?µg/mL. At sub-MICs and 1× MIC, ASP-1 showed a strong antibiofilm characteristic. ASP-1 at a concentration of 128?µg/mL did not show haemolytic activity, and no cytotoxicity was observed against hepatic carcinoma and breast carcinoma cell lines at the same concentration. Peptide ASP-1 with anti-MRSA and antibiofilm abilities and non-haemolytic and non-cytotoxic properties has not been reported previously. These findings suggest that it may serve as a lead molecule for developing alternative topical antibacterial agents.