Hypochlorous acid in a double formulation (liquid plus gel) is a key prognostic factor for healing and absence of infection in chronic ulcers. A nonrandomized concurrent treatment study.

Background and Aims: Diverse protocols prevent infection and/or improve ulcer epithelialization. The existing protocols tend to antagonize the risk factors that promote the chronicity of this type of wound. Hypochlorous acid (HOCl) is used to treat ulcers and wounds because of its antiseptic and noncytotoxic properties. Its liquid form is effective but has little residual effect, while in gel it has more residual power. Methods: An experimental nonrandomized study has been carried out treating 346 chronic ulcers of various etiologies in 220 patients. Ulcer outcomes were originally classified as: "complete healing," "incomplete healing without infection," and "incomplete healing with infection." Various antiseptic solutions were used as ulcers cleaning solutions: liquid HOCl, gel HOCl, polymeric biguanide, or chlorhexidine. Only one was applied to the lesion as monotherapy. But, in other cases, we used a combined HOCl (liquid then gel: bitherapy). Bivariate (Chi-square and variance tests) and multivariate studies (logistic regression) evaluated associations of ulcer characteristics and mono or bitherapy outcomes. Results: Four factors reduce the probability of complete ulcer healing: patient age (odds ratio [OR]: 0.97); weeks of ulcer evolution (OR: 0.99); poor granulation on admission (OR: 0.35); and need for antibiotic therapy (OR: 0.41). One factor favored healing: combined HOCl therapy with liquid plus gel (OR: 4.8). Infections were associated with longer times of evolution (OR: 1.002) and bad odor of the ulcer on admission (OR: 14), but bitreatment with HOCl reduced the risk of infection (OR: 0.3). Conclusion: A double HOCl formulation (liquid plus gel) reduces the probability of poor healing and infection, in chronic ulcers of various etiologies.

Synergistic effect of two formulations of hypochlorous acid in the treatment of 346 chronic ulcers.

Our objective was to assess the efficacy of two successive applications of hypochlorous acid, first as a liquid and then as a gel because liquid hypochlorous acid is effective but has little residual effect, while the gel form has more residual power, and compare it with that of other products. An experimental non-randomised study was carried out, treating 346 chronic ulcers in 220 patients. The antiseptic treatment has been divided into 'hypochlorous acid' (Clortech), 'hypochlorous acid liquid + gel' (Clortech + Microdacyn60R -hydrogel) and 'Others' (Prontosan or Chlorhexidine or Microdacyn60R -hydrogel). Bivariate and multivariate studies analysed the characteristics of the patients and their ulcers, including size, symptoms, signs, treatments received and their duration, and so on. The ulcers were complicated, of long evolution, and most had a vascular origin. On average, antiseptic treatment lasted 14 weeks. At the time of their discharge, or last treatment in the clinics, 59% of the ulcers had healed completely, 9.5% worsened, and 6.9% had become infected during this period. In the bivariate and multivariate studies, we took as reference the 'others' treatments that showed no significant differences in healing time or infection rates compared with liquid hypochlorous acid 100-500 mg/L alone. However, hypochlorous acid liquid + gel showed a synergistic effect, with a higher probability of achieving complete healing (four times) and a lower probability of infection (a fifth), compared to the 'other' antiseptics. In conclusion, a synergistic effect was found with the successive application of hypochlorous acid in liquid followed by gel, an effect that increased healing probability and decreased the risk of the ulcer becoming infected.

Global Methylome Scores Correlate with Histological Subtypes of Colorectal Carcinoma and Show Different Associations with Common Clinical and Molecular Features.

BACKGROUND: The typical methylation patterns associated with cancer are hypermethylation at gene promoters and global genome hypomethylation. Aberrant CpG island hypermethylation at promoter regions and global genome hypomethylation have not been associated with histological colorectal carcinomas (CRC) subsets. Using Illumina's 450 k Infinium Human Methylation beadchip, the methylome of 82 CRCs were analyzed, comprising different histological subtypes: 40 serrated adenocarcinomas (SAC), 32 conventional carcinomas (CC) and 10 CRCs showing histological and molecular features of microsatellite instability (hmMSI-H), and, additionally, 35 normal adjacent mucosae. Scores reflecting the overall methylation at 250 bp, 1 kb and 2 kb from the transcription starting site (TSS) were studied. RESULTS: SAC has an intermediate methylation pattern between CC and hmMSI-H for the three genome locations. In addition, the shift from promoter hypermethylation to genomic hypomethylation occurs at a small sequence between 250 bp and 1 Kb from the gene TSS, and an asymmetric distribution of methylation was observed between both sides of the CpG islands (N vs. S shores). CONCLUSION: These findings show that different histological subtypes of CRC have a particular global methylation pattern depending on sequence distance to TSS and highlight the so far underestimated importance of CpGs aberrantly hypomethylated in the clinical phenotype of CRCs.

Subjective assessment reported by patients shows differences between single-bundle and double-bundle anterior cruciate ligament reconstruction, systematic review and meta-analysis.

To determine the functional recovery, active reincorporation, and anteroposterior and rotational stability of patients undergoing anterior cruciate ligament (ACL) reconstruction using arthroscopy techniques with simple-bundle (SB) or double-bundle (DB). The following databases were searched: PubMed, Embase (Elsevier platform), the Cochrane Central Register of Controlled Trials (Wiley platform), Web of Science, and CINAHL. Level I and II studies involving anterior cruciate ligament arthroscopy were included in the search. Records were screened by title and abstract and assessed the risk of bias of selected studies. Meta-analyses using RevMan 5.3 software were conducted on the following outcomes: knee functionality, objective measurements of knee stability, rotational knee stability and knee anterior stability, sports reincorporation, and subjective assessments. Twenty-four studies of patients undergoing ACL reconstruction were included in the qualitative and quantitative synthesis (1707 patients) for Lysholm score, Subjective International Knee Documentation Committee (IKDC) score, Tegner score, KT-1000/2000, Lachman test, Objective IKDC score, and Pivot-Shift test. A return to pre-injury level showed a significant decrease in the Lysholm score (mean difference, - 0.99; 95% CI - 1.71 to - 0.40; P = 0.007) and Tegner score (mean difference, - 0.07; 95% CI, - 0.13 to - 0.01; P = 0.02) at DB reconstruction, similar to the knee functionality outcome of the subjective IKDC score (mean difference - 1.42; 95% CI - 2.46 to - 0.38; P = 0.007). There is no clear or significant difference in clinical stability and knee function or in sports incorporation with the true difference occurring in the subjective assessment.

Surface Disinfectants for Burn Units Evaluated by a New Double Method, Using Microorganisms Recently Isolated From Patients, on a Surface Germ-Carrier Model.

Assessment methods of surface disinfection based on international standards (Environmental Protection Agency, European Norms, etc) do not correspond to hospital reality. New evaluation methods of surfaces disinfection are proposed to choose the most suitable disinfectant to act against clinically relevant microorganisms detected on the surfaces of burn units. 1) "Immediate effect": 6 products were compared using a glass germ-carrier and 20 recently isolated microorganisms from different patients in the intensive care units. Disinfectants were applied with microfiber cloths. Log10 reductions were calculated for colony forming units produced after 15 minutes of disinfectant application. 2) "Residual effect": the glass germ-carriers were previously impregnated with one of the studied disinfectants. After a 30-minute wait period, they were then contaminated with 1 microorganism (from the 20 above-mentioned). After 15 minutes, the disinfectant was inhibited and the log10 reduction of colony forming units was assessed. The immediate effect (disinfection and microorganism dragging and transferring from the surface to the cloth) produced complete elimination of the inoculums for all products used except one (a diluted quaternary ammonium). The average residual effect found on the 20 microorganisms was moderate: 2 to 3 log10 colony forming unit reduction with chlorine dioxide or 0.5% chlorhexidine (and lower with the other products), obtaining surfaces refractory to recontamination, at least, during 30 minutes. Two tests should be performed before advising surface disinfectant: 1) direct effect and 2) residual efficacy. These characteristics should be considered when a new surface disinfectant is chosen. Chlorine dioxide has a similar or better direct effect than sodium hypochlorite and a similar residual effect than chlorhexidine.

Preclinical models of atherosclerosis. The future of Hybrid PET/MR technology for the early detection of vulnerable plaque.

Cardiovascular diseases are the leading cause of death in developed countries. The aetiology is currently multifactorial, thus making them very difficult to prevent. Preclinical models of atherothrombotic diseases, including vulnerable plaque-associated complications, are now providing significant insights into pathologies like atherosclerosis, and in combination with the most recent advances in new non-invasive imaging technologies, they have become essential tools to evaluate new therapeutic strategies, with which can forecast and prevent plaque rupture. Positron emission tomography (PET)/computed tomography imaging is currently used for plaque visualisation in clinical and pre-clinical cardiovascular research, albeit with significant limitations. However, the combination of PET and magnetic resonance imaging (MRI) technologies is still the best option available today, as combined PET/MRI scans provide simultaneous data acquisition together with high quality anatomical information, sensitivity and lower radiation exposure for the patient. The coming years may represent a new era for the implementation of PET/MRI in clinical practice, but first, clinically efficient attenuation correction algorithms and research towards multimodal reagents and safety issues should be validated at the preclinical level.

EMMPRIN-Targeted Magnetic Nanoparticles for In Vivo Visualization and Regression of Acute Myocardial Infarction.

UNLABELLED: Inhibition of extracellular matrix (ECM) degradation may represent a mechanism for cardiac protection against ischemia. Extracellular matrix metalloproteinase inducer (EMMPRIN) is highly expressed in response to acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including gelatinases MMP-2 and MMP-9. We targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles conjugated with the EMMPRIN binding peptide AP-9 (NAP9), or an AP-9 scrambled peptide as a negative control (NAPSC). We found that NAP9 binds to endogenous EMMPRIN in cultured HL1 myocytes and in mouse hearts subjected to ischemia/reperfusion (IR). Injection of NAP9 at the time of or one day after IR, was enough to reduce progression of myocardial cell death when compared to CONTROL and NAPSC injected mice (infarct size in NAP9 injected mice: 32%±6.59 vs CONTROL: 46%±9.04 or NAPSC injected mice: 48%±7.64). In the same way, cardiac parameters were recovered to almost healthy levels (LVEF NAP9 63% ± 7.24 vs CONTROL 42% ± 4.74 or NAPSC 39% ± 6.44), whereas ECM degradation was also reduced as shown by inhibition of MMP-2 and MMP-9 activation. Cardiac magnetic resonance (CMR) scans have shown a signal enhancement in the left ventricle of NAP9 injected mice with respect to non-injected, and to mice injected with NAPSC. A positive correlation between CMR enhancement and Evans-Blue/TTC staining of infarct size was calculated (R:0.65). Taken together, these results point to EMMPRIN targeted nanoparticles as a new approach to the mitigation of ischemic/reperfusion injury.

Experimental infection of European red deer (Cervus elaphus) with bluetongue virus serotypes 1 and 8.

Bluetongue (BT) is a climate change-related emerging infectious disease in Europe. Outbreaks of serotypes 1, 2, 4, 6, 8, 9, 11, and 16 are challenging Central and Western Europe since 1998. Measures to control or eradicate bluetongue virus (BTV) from Europe have been implemented, including movement restrictions and vaccination of domestic BTV-susceptible ruminants. However, these measures are difficult to apply in wild free-ranging hosts of the virus, like red deer (Cervus elaphus), which could play a role in the still unclear epidemiology of BT in Europe. We show for the first time that BTV RNA can be detected in European red deer blood for long periods, comparable to those of domestic ruminants, after experimental infection with BTV-1 and BTV-8. BTV RNA was detected in experimentally infected red deer blood up to the end of the study (98-112 dpi). BTV-specific antibodies were found in serum both by enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VNT) from 8 to 12 dpi to the end of the study, peaking at 17-28 dpi. Our results indicate that red deer can be infected with BTV and maintain BTV RNA for long periods, remaining essentially asymptomatic. Thus, unvaccinated red deer populations have the potential to be a BT reservoir in Europe, and could threaten the success of the European BTV control strategy. Therefore, wild and farmed red deer should be taken into account for BTV surveillance, and movement restrictions and vaccination schemes applied to domestic animals should be adapted to include farmed or translocated red deer.