Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-Debridement Antibiotic Treatment for 10 versus 20 days

Background: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot (ST-DFI) remains unknown. Objective: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for ST-DFI results in similar rates of clinical remission and adverse events (AE). Summary Background Data: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. Methods: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of “clinical remission at two-months follow-up”. Results: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat (ITT) population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm (p = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; p = 0.71), and remission in the per-protocol (PP) population (25/32 vs. 18/27; p = 0.32). Overall, eight soft tissue DFIs in the 10-day arm and five cases in the 20-day arm recurred as a new osteomyelitis (8/35 [23%] versus 5/31 [16%]; p = 0.53). Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (ITT population, hazard ratio 0.6, 95%CI 0.3-1.1; PP population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. Conclusions: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way

Structures of the Signal Recognition Particle Receptor from the Archaeon Pyrococcus furiosus: Implications for the Targeting Step at the Membrane

In all organisms, a ribonucleoprotein called the signal recognition particle (SRP) and its receptor (SR) target nascent proteins from the ribosome to the translocon for secretion or membrane insertion. We present the first X-ray structures of an archeal FtsY, the receptor from the hyper-thermophile Pyrococcus furiosus (Pfu), in its free and GDP•magnesium-bound forms. The highly charged N-terminal domain of Pfu-FtsY is distinguished by a long N-terminal helix. The basic charges on the surface of this helix are likely to regulate interactions at the membrane. A peripheral GDP bound near a regulatory motif could indicate a site of interaction between the receptor and ribosomal or SRP RNAs. Small angle X-ray scattering and analytical ultracentrifugation indicate that the crystal structure of Pfu-FtsY correlates well with the average conformation in solution. Based on previous structures of two sub-complexes, we propose a model of the core of archeal and eukaryotic SRP•SR targeting complexes

Is routine measurement of the serum C-reactive protein level helpful during antibiotic therapy for diabetic foot infection?

Clinicians frequently monitor serum C-reactive protein (CRP) levels during therapy for diabetic foot infections (DFIs), but evidence supporting this is unclear. Using a database from prospective controlled DFI trials, with fixed duration of antibiotic therapy, we correlated the CRP levels at study enrolment and at end of therapy (EOT). Among 159 DFI episodes, 93 involved the bone and 66 the soft tissues. Overall, treatment cured 122 infections (77%), while 37 episodes (23%) recurred after a median of 53 days. The median CRP in the groups with cure versus failure differed minimally at enrolment (median 67 vs. 81 mg/L) or EOT (7 vs. 10 mg/L). Similarly, there was negligible difference in the percentage of CRP levels that normalized at EOT (39% vs. 35%). In our prospective cohorts, a blunt iterative monitoring of CRP during DFI treatment, without correlation with clinical findings, failed to predict treatment failures

Soft X-ray Microscopy Techniques for Medical and Biological Imaging at TwinMic\u2014Elettra

Progress in nanotechnology calls for material probing techniques of high sensitivity and resolution. Such techniques are also used for high-impact studies of nanoscale materials in medicine and biology. Soft X-ray microscopy has been successfully used for investigating complex biological processes occurring at micrometric and sub-micrometric length scales and is one of the most powerful tools in medicine and the life sciences. Here, we present the capabilities of the TwinMic soft X-ray microscopy end-station at the Elettra synchrotron in the context of medical and biological imaging, while we also describe novel uses and developments

Copper Oxide Nanomaterial Fate in Plant Tissue: Nanoscale Impacts on Reproductive Tissues

A thorough understanding of the implications of chronic low-dose exposure to engineered nanomaterials through the food chain is lacking. The present study aimed to characterize such a response in Cucurbita pepo L. (zucchini) upon exposure to a potential nanoscale fertilizer: copper oxide (CuO) nanoparticles. Zucchini was grown in soil amended with nano-CuO, bulk CuO (100 mg Kg-1), and CuSO4 (320 mg Kg-1) from germination to flowering (60 days). Nano-CuO treatment had no impact on plant morphology or growth nor pollen formation and viability. The uptake of Cu was comparable in the plant tissues under all treatments. RNA-seq analyses on vegetative and reproductive tissues highlighted common and nanoscale-specific components of the response. Mitochondrial and chloroplast functions were uniquely modulated in response to nanomaterial exposure as compared with conventional bulk and salt forms. X-ray absorption spectroscopy showed that the Cu local structure changed upon nano-CuO internalization, suggesting potential nanoparticle biotransformation within the plant tissues. These findings demonstrate the potential positive physiological, cellular, and molecular response related to nano-CuO application as a plant fertilizer, highlighting the differential mechanisms involved in the exposure to Cu in nanoscale, bulk, or salt forms. Nano-CuO uniquely stimulates plant response in a way that can minimize agrochemical inputs to the environment and therefore could be an important strategy in nanoenabled agriculture

Genetic Regulation of Plasma Lipid Species and Their Association with Metabolic Phenotypes

ISSN:2405-472