Molecular Dynamics Characterization of Radiosensitizing Coated Gold Nanoparticles in Aqueous Environment.

Functionalized metal nanoparticles (NPs) have been proposed as promising radiosensitizing agents for more efficient radiotherapy treatment using photons and ion beams. Radiosensitizing properties of NPs may depend on many different parameters (such as size, composition, and density) of the metal core, the organic coatings, and the molecular environment. A systematic exploration of each of these parameters on the atomistic level remains a formidable and costly experimental task, but it can be addressed by means of advanced computational modeling. This paper describes a detailed computational procedure for construction and atomistic-level characterization of radiosensitizing metal NPs in explicit molecular media. The procedure is general and is extensible to many different combinations of the core, coating, and environment. As an illustrative and experimentally relevant case study, we consider nanometer-sized gold NPs coated with thiol-poly(ethylene glycol)-amine molecules of different length and surface density and solvated in water at ambient conditions. The radial distribution of different atoms in the coatings as well as distribution and structural properties of water around the coated NPs are analyzed and linked to radiosensitizing properties of the NPs. It is revealed that the structure of the coating layer on the solvated NPs depends strongly on the surface density of ligands. At surface densities below ∼3 molecules/nm2 the coating represents a mixture of different conformation states, whereas elongated "brush"-like structures are formed at higher densities of ligands. The water content in denser coatings is significantly lower at distances from 1 nm up to 3 nm from the gold surface depending on the length of ligand molecules. Such dense and thick coatings may suppress the production of hydroxyl radicals by low-energy electrons emitted from the metal NPs and thus diminish their radiosensitizing properties. The presented computational framework provides precise information for a quantitative atomistic-level description of the structural properties of coated metal NPs in biologically relevant environments and so may form a basis for future developments to achieve a more realistic description of irradiation-driven chemistry effects in the vicinity of coated metal NPs.

Are Surrogate Markers for Diabetic Foot Osteomyelitis Remission Reliable?

BACKGROUND: We aimed to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections (DFIs). METHODS: Thirty-five patients with DFIs were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histologic analysis initially and for recurrence. Fisher exact and χ2 tests were used for dichotomous variables and Student t and Mann-Whitney U tests for continuous variables (α = .05). RESULTS: Twenty-four patients were diagnosed as having osteomyelitis and 11 as having soft-tissue infections. Four patients (16.7%) with osteomyelitis had reinfection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), reulceration (20.8%), readmission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed as having osteomyelitis versus soft-tissue infections. There were no differences in osteomyelitis reinfection (16.7% versus 45.5%; P = .07), wounds that failed to heal (8.3% versus 9.1%; P = .94), reulceration (20.8% versus 27.3%; P = .67), readmission for DFIs at the same site (16.7% versus 36.4%; P = .20), amputation at the same site after discharge (12.5% versus 36.4%; P = .10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate of 8.3% to 20.8%. CONCLUSIONS: Most osteomyelitis markers were similar to markers in soft-tissue infection. Commonly reported surrogate markers were not shown to be specific to identify patients who failed osteomyelitis treatment compared with patients with soft-tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis.

In this study, we assessed the effectiveness of inflammatory markers to diagnose and monitor the treatment of osteomyelitis in the diabetic foot. We evaluated 35 consecutive patients admitted to our hospital with infected foot ulcers. Patients were divided in two groups based on the results of bone culture and histopathology: osteomyelitis and no osteomyelitis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNFα), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP1α) were measured at baseline after 3 and 6 weeks of standard therapy. PCT levels in the osteomyelitis group were significantly higher at baseline than in the group with no osteomyelitis (P = 0·049). There were no significant differences between the two groups in the levels of the other markers. CRP, ESR, PCT and IL-6 levels significantly declined in the group with osteomyelitis after starting therapy, while MCP-1 increased (P = 0·002). TNFα and MIP1α levels were below range in 80 out of 97 samples and therefore not reported. Our results suggest that PCT might be useful to distinguish osteomyelitis in infected foot ulcers. CRP, ESR, PCT and IL-6 are valuable when monitoring the effect of therapy.

Hybrid imaging with 99mTc-WBC SPECT/CT to monitor the effect of therapy in diabetic foot osteomyelitis.

This study sought to assess the utility of monitoring response to treatment of diabetic foot osteomyelitis (DFO) with Tc-99m WBC-labelled single photon emission computed tomography (SPECT/CT) imaging. This is a retrospective cohort study of 20 patients with DFO with sequential Tc-99m WBC-labelled SPECT/CT imaging. Radiologic findings of osteomyelitis were evaluated and imaging results were correlated with clinical outcomes subtracted from chart review. Successful treatment of osteomyelitis was defined by wound healing and/or lack of re-admission for bone infection of the same site within 1 year. The sensitivity, specificity, positive predictive value and negative predictive value of SPECT/CT to determine osteomyelitis treatment remission were 90%, 56%, 69% and 83%, respectively. Tc-99m WBC-labelled SPECT/CT imaging may be useful to help determine treatment outcomes for DFO.

Treatment options for venous leg ulcers: effectiveness of vascular surgery, bioengineered tissue, and electrical stimulation.

OBJECTIVE: To evaluate the peer-reviewed literature that compares advanced venous leg ulcer therapies to standard of care with compression dressings. METHODS: A MEDLINE search for venous ulcer treatment with electrical stimulation, surgical vein correction, and bioengineered tissues was conducted. Randomized clinical trials comparing advanced treatment with standard of care using compression dressing were included. A total of 7 bioengineered tissue, 4 surgical treatment, and 4 electrical stimulation randomized clinical trials were identified. RESULTS: Compared with nonstandard treatments, electrical stimulation demonstrated improved wound healing, fewer adverse events, and shorter duration of healing. Healing rates at the end of the study were greater for surgical intervention, followed by similar outcomes for electrical stimulation and bioengineered tissues. Studies involving bioengineered tissues and surgical venous ablation demonstrated inconsistent/inconclusive results. CONCLUSIONS: Utilization of electrical stimulation in venous ulcer management has not been fully explored. Further studies of dosing electrical stimulation therapy may reveal therapeutic and preventive benefits for managing venous ulcers not yet elucidated.

A planar three-coordinate vanadium(II) complex and the study of terminal vanadium nitrides from N2: a kinetic or thermodynamic impediment to N-N bond cleavage?

We report the first mononuclear three-coordinate vanadium(II) complex [(nacnac)V(ODiiP)] and its activation of N2 to form an end-on bridging dinitrogen complex with a topologically linear V(III)N2V(III) core and where each vanadium center antiferromagnetically couples to give a ground state singlet with an accessible triplet state as inferred by HFEPR spectroscopy. In addition to investigating the conversion of N2 to the terminal nitride (as well as the microscopic reverse process), we discuss its similarities and contrasts to the isovalent d(3) system, [Mo(N[(t)Bu]Ar)3], and the S = 1 system [(Ar[(t)Bu]N)3Mo]2(µ2-η(1):η(1)-N2).