Evolution of Resistance against Ciprofloxacin, Tobramycin, and Trimethoprim/Sulfamethoxazole in the Environmental Opportunistic Pathogen Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an opportunistic pathogen that produces respiratory infections in immunosuppressed and cystic fibrosis patients. The therapeutic options to treat S. maltophilia infections are limited since it exhibits resistance to a wide variety of antibiotics such as ß-lactams, aminoglycosides, tetracyclines, cephalosporins, macrolides, fluoroquinolones, or carbapenems. The antibiotic combination trimethoprim/sulfamethoxazole (SXT) is the treatment of choice to combat infections caused by S. maltophilia, while ceftazidime, ciprofloxacin, or tobramycin are used in most SXT-resistant infections. In the current study, experimental evolution and whole-genome sequencing (WGS) were used to examine the evolutionary trajectories of S. maltophilia towards resistance against tobramycin, ciprofloxacin, and SXT. The genetic changes underlying antibiotic resistance, as well as the evolutionary trajectories toward that resistance, were determined. Our results determine that genomic changes in the efflux pump regulatory genes smeT and soxR are essential to confer resistance to ciprofloxacin, and the mutation in the rplA gene is significant in the resistance to tobramycin. We identified mutations in folP and the efflux pump regulator smeRV as the basis of SXT resistance. Detailed and reliable knowledge of ciprofloxacin, tobramycin, and SXT resistance is essential for safe and effective use in clinical settings. Herein, we were able to prove once again the extraordinary ability that S. maltophilia has to acquire resistance and the importance of looking for alternatives to combat this resistance.

Transcriptomic profiling of an evolved Yarrowia lipolytica strain: tackling hexanoic acid fermentation to increase lipid production from short-chain fatty acids.

BACKGROUND: Short-chain fatty acids (SCFAs) are cost-effective carbon sources for an affordable production of lipids. Hexanoic acid, the acid with the longest carbon chain in the SCFAs pool, is produced in anaerobic fermentation of organic residues and its use is very challenging, even inhibiting oleaginous yeasts growth. RESULTS: In this investigation, an adaptive laboratory evolution (ALE) was performed to improve Yarrowia lipolytica ACA DC 50109 tolerance to high hexanoic acid concentrations. Following ALE, the transcriptomic analysis revealed several genetic adaptations that improved the assimilation of this carbon source in the evolved strain compared to the wild type (WT). Indeed, the evolved strain presented a high expression of the up-regulated gene YALI0 E16016g, which codes for FAT1 and is related to lipid droplets formation and responsible for mobilizing long-chain acids within the cell. Strikingly, acetic acid and other carbohydrate transporters were over-expressed in the WT strain. CONCLUSIONS: A more tolerant yeast strain able to attain higher lipid content under the presence of high concentrations of hexanoic acid has been obtained. Results provided novel information regarding the assimilation of hexanoic acid in yeasts.

Magnetoelastic Coupling Evidence by Anisotropic Crossed Thermal Expansion in Magnetocaloric RSrCoFeO6 (R = Sm, Eu) Double Perovskites.

Double perovskite oxides, characterized by their tunable magnetic properties and robust interconnection between the lattice and magnetic degrees of freedom, present an enticing foundation for advanced magnetic refrigeration materials. Herein, we delve into the influence of rare-earth elements on RSrCoFeO6 (R = Sm, Eu) disordered double perovskites by examining their structural, electronic, magnetic, and magnetocaloric properties. Temperature-dependent synchrotron X-ray diffraction analysis confirmed the stability of the orthorhombic phase (Pnma) across a wide temperature range. X-ray photoemission spectroscopy revealed that both Sm and Eu are in the 3+ state, whereas multiple states for Co2+/3+ and Fe3+/4+ are identified. The magnetic investigation and magnetocaloric effect (MCE) analysis brought to light the presence of a long-range antiferromagnetic (AFM) order with a second-order phase transition (SOPT) in both samples. The maximum magnetic entropy change ΔSMmax was approximately 0.9 J/kg K for both samples at applied field 0-7 T, manifesting prominently above Neel temperatures TN ≈ 93 K (Sm) and 84 K (Eu). Nevertheless, different relative cooling powers (RCP) of 112.6 J/kg (Sm) and 95.5 J/kg (Eu) were observed. A detailed analysis of the temperature-dependent lattice parameters shed light on a distinct magnetocaloric effect across the magnetic transition temperature, unveiling an anisotropic thermal expansion [αV = 1.41 × 10-5 K-1 (Sm) and αV = 1.54 × 10-5 K-1 (Eu)] wherein the thermal expansion axial ratio αbSm/αbEu = 0.61 became lower with increasing temperature, which suggests that the Eu sample experiences a greater thermal expansion in the b-axis direction. At the atomic bonding level, the evidence for magnetoelastic coupling around the magnetic transition temperatures TN was found through the anomalies along the average Co/Fe-O bond distance, formal valence, octahedral distortion, as well as an anisotropic lattice expansion.

Randomized Double-blind Cost-effectiveness Comparison of Two 10% Urea Creams in Patients with Diabetic Foot Syndrome.

OBJECTIVE: To evaluate the cost-effectiveness of two 10% urea creams in patients with diabetic foot syndrome. METHODS: This was a prospective, longitudinal, single-center, randomized, double-blind, prospective clinical trial that evaluated the skin quality of 20 feet belonging to 10 patients with diabetic foot syndrome after the application of two 10% urea creams purchased from pharmacies and supermarkets. RESULTS: At follow-up, 19 (95%) of the participants' feet showed improved skin quality, irrespective of the cream applied. On visual inspection, participants had a decreased presence of xerosis, hyperkeratosis, and preulcerative signs such as subkeratotic bruising and areas of redness on the dorsum of the toes. At the 3-month follow-up, nine (90%) of the participants stated that they had continued to apply the cream as a method of self-management to prevent complications. CONCLUSIONS: Creams containing 10% urea purchased in supermarkets improve foot skin quality in patients with diabetic foot syndrome, regardless of their cost. Based on these findings, the authors recommend creams containing 10% urea as a self-management tool for patients with diabetic foot syndrome.

M.O.I.S.T. Concept for the Local Therapy of Chronic Wounds: An International Update.

Chronic wounds remain a significant clinical challenge both for those affected and for healthcare systems. The treatment is often comprised and complex. All patients should receive wound care that is integrated into a holistic approach involving local management that addresses the underlying etiology and provides for gold standard therapy to support healing, avoid complications and be more cost effective. There have been significant advances in medicine over the last few decades. The development of new technologies and therapeutics for the local treatment of wounds is also constantly increasing. To help standardize clinical practice with regard to the multitude of wound products, the M.O.I.S.T. concept was developed by a multidisciplinary expert group. The M stands for moisture balance, O for oxygen balance, I for infection control, S for supporting strategies, and T for tissue management. Since the M.O.I.S.T. concept, which originated in the German-speaking countries, is now intended to provide healthcare professionals with an adapted instrument to be used in clinical practice, and a recent update to the concept has been undertaken by a group of interdisciplinary experts to align it with international standards. The M.O.I.S.T. concept can now be used internationally both as an educational tool and for the practical implementation of modern local treatment concepts for patients with chronic wounds and can also be used in routine clinical practice.

Diagnostic Performance of Atherogenic Index of Plasma for Predicting Diabetic Foot Osteomyelitis with Peripheral Artery Disease.

Background: This study aims to assess the atherogenic index of plasma (AIP) diagnostic value in detecting diabetic foot osteomyelitis (DFO) among patients with diabetic foot ulcers (DFUs). Methods: A prospective cohort study was conducted on 80 patients with DFUs and suspected DFO between January 2022 and December 2023. The primary outcome measures included the diagnosis of DFO, determined by positive microbiological analysis results from bone samples and its correlation with the AIP. Receiver operating characteristic (ROC) curves were utilized to select the optimal diagnostic cut-off points for AIP and post hoc analysis was performed to evaluate the difference in the AIP for diagnosing DFO in patients with and without peripheral arterial disease (PAD). Results: The diagnostic potential for DFO in PAD patients of AIP-1 (Log TC/HDL) showed an AUC of 0.914 (p < 0.001 [0.832-0.996]), leading to a sensitivity of 83% and a specificity of 85%. By contrast, AIP-2 (Log TG/HDL) demonstrated a slightly lower AUC of 0.841 (p < 0.001 [0.716-0.967]), leading to a sensitivity of 76% and a specificity of 74%. Conclusions: The AIP tool, with its ideal blend of sensitivity and specificity, aids in predicting DFO effectively. Therefore, clinicians should consider using AIP for patients suffering from PAD and associated DFO.

Tailoring Mesoporous Silica-Coated Silver Nanoparticles and Polyurethane-Doped Films for Enhanced Antimicrobial Applications.

The global increase in multidrug-resistant bacteria poses a challenge to public health and requires the development of new antibacterial materials. In this study, we examined the bactericidal properties of mesoporous silica-coated silver nanoparticles, varying the core sizes (ca. 28 nm and 51 nm). We also investigated gold nanoparticles (ca. 26 nm) coated with mesoporous silica as possible inert metal cores. To investigate the modification of antimicrobial activity after the surface charge change, we used silver nanoparticles with a silver core of 28 nm coated with a mesoporous shell (ca. 16 nm) and functionalized with a terminal amine group. Furthermore, we developed a facile method to create mesoporous silica-coated silver nanoparticles (Ag@mSiO2) doped films using polyurethane (IROGRAN®) as a polymer matrix via solution casting. The antibacterial effects of silver nanoparticles with different core sizes were analyzed against Gram-negative and Gram-positive bacteria relevant to the healthcare and food industry. The results demonstrated that gold nanoparticles were inert, while silver nanoparticles exhibited antibacterial effects against Gram-negative (Escherichia coli and Salmonella enterica subsp. enterica serovar Choleraesuis) and Gram-positive (Bacillus cereus) strains. In particular, the larger Ag@mSiO2 nanoparticles showed a minimum inhibitory concentration (MIC) and a minimum bactericidal concentration (MBC) of 18 µg/mL in the Salmonella strain. Furthermore, upon terminal amine functionalization, reversing the surface charge to positive values, there was a significant increase in the antibacterial activity of the NPs compared to their negative counterparts. Finally, the antimicrobial properties of the nanoparticle-doped polyurethane films revealed a substantial improvement in antibacterial efficacy. This study provides valuable information on the potential of mesoporous silica-coated silver nanoparticles and their applications in fighting multidrug-resistant bacteria, especially in the healthcare and food industries.

Mutations in the efflux pump regulator MexZ shift tissue colonization by Pseudomonas aeruginosa to a state of antibiotic tolerance.

Mutations in mexZ, encoding a negative regulator of the expression of the mexXY efflux pump genes, are frequently acquired by Pseudomonas aeruginosa at early stages of lung infection. Although traditionally related to resistance to the first-line drug tobramycin, mexZ mutations are associated with low-level aminoglycoside resistance when determined in the laboratory, suggesting that their selection during infection may not be necessarily, or only, related to tobramycin therapy. Here, we show that mexZ-mutated bacteria tend to accumulate inside the epithelial barrier of a human airway infection model, thus colonising the epithelium while being protected against diverse antibiotics. This phenotype is mediated by overexpression of lecA, a quorum sensing-controlled gene, encoding a lectin involved in P. aeruginosa tissue invasiveness. We find that lecA overexpression is caused by a disrupted equilibrium between the overproduced MexXY and another efflux pump, MexAB, which extrudes quorum sensing signals. Our results indicate that mexZ mutations affect the expression of quorum sensing-regulated pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within patients, something unnoticeable using standard laboratory tests.

Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance.

PURPOSE: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. METHODS: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. RESULTS: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. CONCLUSION: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.

Low Cubilin/Myeloperoxidase ratio as a promising biomarker for prognosis of high-grade T1 bladder cancer.

PURPOSE: T1 bladder cancer is known for its high progression and recurrence rates. Identifying aggressive tumours at the non-muscle-invasive stage is crucial to allow early interventions and subsequently increase patient survival. This study aimed to investigate the potential of the cubilin/myeloperoxidase (CUBN/MPO) ratio as a high-grade T1 bladder cancer biomarker. METHODS: Urine samples were collected from 30 patients who underwent transurethral resection of the tumour with high-grade T1 bladder cancer (June 2015 to December 2019) before surgery. The urinary proteome was analysed using high-resolution mass spectrometry and the CUBN/MPO ratio was calculated. The primary outcome was the recurrence during the follow-up (around 31.5 months after resection). Univariate Cox regression and Kaplan-Meier curves were used for data analysis. RESULTS: Patients with a low CUBN/MPO ratio exhibited upregulated MPO and/or downregulated CUBN. This group of patients had a higher incidence of disease recurrence and progression. Low CUBN/MPO ratio was significantly associated with a higher likelihood of recurrence, progression, and death. It is worth noting that this study was exploratory and conducted on a small sample size, so further research is needed to validate these findings in larger cohorts. CONCLUSION: This study highlights the potential of the CUBN/MPO ratio as a prognostic biomarker for high-grade T1 bladder cancer.

Does HPV biotype influence the characteristics and evolution of plantar warts?

BACKGROUND: Few studies have addressed the relationship of human papillomavirus (HPV) biotypes to patient characteristics and the clinical signs, course, and response to the treatment of plantar warts. OBJECTIVE: Analyze the HPV types associated with plantar warts and their relationship with warts characteristics, patient characteristics and response to treatment. METHODS: A total of 372 patients sampled for hyperkeratosis of a plantar wart were included. Multiplex polymerase chain reaction (PCR) was performed to detect the HPV biotype. RESULTS: The prevalence of HPV was 81.2%, and HPV1 was the most prevalent biotype (36.1%). HPV1 was the most prevalent biotype in patients < 70 years old (90.9% in < 10 years), and biotypes 2, 19 and 27 were the most prevalent in patients > 70 years old (p = 0.012). HPV1 was the most frequent in patients with one (39,9%) or two (47.1%) warts and HPV5 (33.3%) in patients with three warts (p < 0.001). Cure, spontaneous resolution, and recurrence were higher in HPV1 (p < 0.001). HPV14 warts healed the fastest (2 months quartile 1-3 (2.0-2.0)), and HPV5 (10.977 (6.0-20.0)) and HPV27 (7.5 (3.0-10.0)) warts (p = 0.033) took the longest to heal. CONCLUSIONS: HPV biotype is associated with age and the number of warts and appears to influence the natural history of warts and their response to treatment.

Fluid handling by foam wound dressings: From engineering theory to advanced laboratory performance evaluations.

This article describes the contemporary bioengineering theory and practice of evaluating the fluid handling performance of foam-based dressings, with focus on the important and clinically relevant engineering structure-function relationships and on advanced laboratory testing methods for pre-clinical quantitative assessments of this common type of wound dressings. The effects of key wound dressing material-related and treatment-related physical factors on the absorbency and overall fluid handling of foam-based dressings are thoroughly and quantitively analysed. Discussions include exudate viscosity and temperature, action of mechanical forces and the dressing microstructure and associated interactions. Based on this comprehensive review, we propose a newly developed testing method, experimental metrics and clinical benchmarks that are clinically relevant and can set the standard for robust fluid handling performance evaluations. The purpose of this evaluative framework is to translate the physical characteristics and performance determinants of a foam dressing into achievable best clinical outcomes. These guiding principles are key to distinguishing desirable properties of a dressing that contribute to optimal performance in clinical settings.

Evaluation of usability, adherence, and clinical efficacy of therapeutic footwear in persons with diabetes at moderate to high risk of diabetic foot ulcers: A multicenter prospective study.

OBJECTIVE: To evaluate therapeutic footwear expectations and usability of individuals with diabetes and foot complications. DESIGN: A prospective multicenter study was conducted on participants with a high risk of developing a diabetic foot ulcer. SETTING: Participants were enrolled in 11 different specialized diabetic foot units in Spain between March 2022 and June 2023. SUBJECTS: Patients with diabetes at moderate to high risk of foot ulceration receiving first therapeutic footwear prescription. INTERVENTIONS: All the patients included in the research were prescribed with their first pair of therapeutic footwear. MAIN MEASURES: Primary outcome measures were MOS-pre and MOS-post questionnaires evaluating use and usability of prescribed therapeutic footwear. Secondary outcome measures aimed to evaluate footwear clinical efficacy as ulceration rate and self-reported perceived walking distance per day. RESULTS: The use of therapeutic footwear exceeded the patient's pre-provision prediction of their anticipated use in 94% of people (n = 126). Based on the visual analogic satisfaction scale, the median satisfaction of daily wearing their therapeutic footwear was 7 points, Interquartile Range (IQR) [5-8.25]. During the follow-up period, 39 participants (29.1%) experienced diabetic foot ulcer. Perceived walking distance participants reported an improvement in their perceived walking ability during various daily life activities. CONCLUSIONS: Diabetes patients at moderate to high risk of diabetic foot ulcer improved their perception of walking ability after therapeutic footwear prescription. Adherence to the therapeutic footwear prescription resulted in less ulcerations.

Inter-observer reliability of the Onychomycosis Severity Index depending on clinical experience: A review of 50 cases.

BACKGROUND: Onychomycosis (ONM) is the most prevalent nail unit pathology, and its severity and monitoring are often based on the visual judgement of clinicians. OBJECTIVE: The objective of this study is to assess the reliability of the Onychomycosis Severity Index (OSI) classification when utilized by three clinicians with varying levels of clinical experience: an experienced podiatrist (with 5 years of experience), a moderately experienced podiatrist (with 2 years of experience) and an inexperienced podiatrist (a recent graduate familiar with the OSI classification but lacking clinical experience). Additionally, we compared the severity assessments made through visual inspection with those determined using the OSI by different clinicians. METHODS: We evaluated reliability using the intraclass correlation index (ICC), analysing 50 images of ONM. RESULTS: The OSI demonstrated a very high level of reliability (ICC: 0.889) across clinicians, irrespective of their experience levels. Conversely, a statistically significant increase in severity was observed when comparing visual assessments with the OSI (p < .001) for ONM severity evaluation. CONCLUSION: The OSI proves to be a reproducible classification system, regardless of the clinical experience of the practitioner employing it.

Disease Knowledge and Behavior Regarding Diabetic Foot Among Persons at Different Risks of Foot Ulceration According to the International Working Group Guidelines.

BACKGROUND: This article aims to analyze levels of knowledge and behavior about diabetic foot care and prevention in persons with diabetes according to International Working Group (IWGDF) risk stratification system. METHODS: A descriptive study in 83 persons with diabetes at different level of risk for foot ulceration (IWGDF risk 0-3). A previously validated questionnaire, the PIN Questionnaire, was used to analyze their levels of understanding of foot complications. Participants were responded on a 5-point Likert scale. RESULTS: IWGDF-3 risk patients knew that good circulation and absence of polyneuropathy in their feet were related to healthy feet relative to the other groups (19.6 ± 2.7, p<.001 and 14.2 ± 0.7, p<.001 respectively). Additionally, they knew that a foot ulcer (DFU) on their feet will not be painful relative to other groups (6.6 ± 2.8, p<.001). High-risk patients knew which physical causes could affect the development of a DFU (18 ± 1.4, p<.001) and that foot self-care and medical control could prevent DFU appearance (23.4 ± 2.15, p<.001 and 13.9 ± 0.9, p<.001 respectively). CONCLUSION: IWGDF-3 patients knew the natural progression of diabetes foot complications and how to prevent them. Clinicians should focus their efforts and educate diabetes at lower risk of foot ulcer.

Role of the phosphotransferase system in the transport of fosfomycin in Escherichia coli.

The inducible inner membrane transporters, UhpT and GlpT are considered to be unique fosfomycin transporters. Glucose-6-phosphate, the substrate for UhpT, enhances fosfomycin activity. Previous work indicates that the fructose phosphotransferase system (PTS) might be involved in fosfomycin transport in the bacterial species, Stenotrophomonas maltophilia. Fosfomycin transport in Escherichia coli has been extensively studied and characterised. The current paper addresses the potential fosfomycin transport activity of the fructose PTS in E. coli. Notably, the deletion of both fructose-specific and general PTS proteins in E. coli increases fosfomycin resistance, which indicates that fructose PTS is involved in fosfomycin transport in E. coli. Further, although inactivation of UhpT, the canonical fosfomycin transporter, in E. coli increases fosfomycin resistance by 2-fold, inactivation of genes encoding the PTS increases it by up to 256-fold. Moreover, intracellular accumulation declines in the absence of both transporters, being mutations in the PTS associated with a larger decline. The results presented in this paper re-open the study of fosfomycin transport and reveal the role of the PTS in the transport of this bactericidal antibiotic in E. coli.

Health-related quality of life among Spanish patients with diabetic foot ulcer according to Diabetic Foot Ulcer Scale - Short Form.

AIM: The aim of this study was to investigate the health-related quality of life of Spanish outpatients with diabetic foot ulcer using the Diabetic Foot Scale-Short Form (DFS-SF). MATERIALS AND METHODS: This cross-sectional observational study included 141 outpatients with diabetic foot ulcers (DFU). The DFS-SF was applied in personal interviews conducted by a trained investigator to assess health-related quality of life (HRQoL). RESULTS: The domain related to "worried about ulcers" had the lowest in score [50 (27.5-65.0)], and the highest score was in the physical health domain [76 (60.0-88.0)]. There was a statistically significant difference in the ulcer type and the physical health subscale, finding the lowest values in the physical health subscale in patients with ischaemic diabetic foot ulcers [58 (39.0-70.0), p = 0.007]. In the multivariable analysis the domains Leisure (OR 0.98, 95% CI 0.97-0.99) and worried about ulcers/feet (OR 0.98, 95% CI 0.96-0.99) were identified as significant independent domains in patients with the experience of a previous minor amputation. A significant negative correlation was observed between the SINBAD DFU score and leisure (r = -0.181, p = 0.032), physical health (r = -0.202, p = 0.016), dependence/daily life (r = -0.232, p = 0.006), and the "bothered by ulcer care" (r = -0.239, p = 0.004) domains of the DFS-SF. The ulcer duration had a significant negative correlation with all the domains of DFS-SF. CONCLUSION: The DFS-SF survey is a specific instrument that could be implemented in diabetic foot units as part of the management of patients with DFU to evaluate HRQoL. The domain of "worried about ulcers" had the lowest score in our population suggesting that clinicians should try to work on the emotional state of patients with DFU. The mean duration of DFU was the most influential factor related to worse scores followed by previous amputations. The SINBAD score had significant negative correlations suggesting that HRQoL may be related to the severity of DFU in this study population.

Hard-to-Heal Wound Healing: Superiority of Hydrogel EHO-85 (Containing Olea europaea Leaf Extract) vs. a Standard Hydrogel. A Randomized Controlled Trial.

Chronic wounds, especially those that are hard-to-heal, constitute a serious public-health problem. Although progress has been made in the development of wound dressings for healing, there is little high-quality evidence of their efficacy, with no evidence of superiority in the use of one hydrogel over another. To evaluate the superiority of a hydrogel (EHO-85), containing Olea europaea leaf extract (OELE), over a standard hydrogel (SH), the promotion and/or improvement of healing of difficult-to-heal wounds was compared in a prospective, parallel-group multicenter, randomized, observer-blinded, controlled trial ("MACAON"). Non-hospitalized patients with pressure, venous or diabetic foot-ulcers difficult-to-heal were recruited and treated with standard care, and EHO-85 (n = 35) or VariHesive (n = 34) as SH. Wound-area reduction (WAR; percentage) and healing rate (HR; mm2/day) were measured. EHO-85 showed a statistically significant superior effect over VariHesive. At the end of the follow-up period, the relative WAR decreased by 51.6% vs. 18.9% (p < 0.001), with a HR mean of 10.5 ± 5.7 vs. 1.0 ± 7.5 mm2/day (p = 0.036). EHO-85 superiority is probably based on its optimal ability to balance the ulcer bed, by modulating pH and oxidative stress. That complements the wetting and barrier functions, characteristics of conventional hydrogels. These results support the use of EHO-85 dressing, for treatment of hard-to-heal ulcers. Trial Registration AEMPS:PS/CR623/17/CE.

The Inactivation of the Putative Two-Component System Sensor PA14_27940 Increases the Susceptibility to Several Antibiotics and Reduces the Motility of Pseudomonas aeruginosa.

The identification of targets whose inactivation increases the activity of antibiotics helps to fight antibiotic resistance. Previous work showed that a transposon-insertion mutant in the gene PA14_27940 increases Pseudomonas aeruginosa susceptibility to aminoglycosides. Since polar effects may affect the phenotype, in the present work, we generated an in-frame PA14_27940 deletion mutant. A PA14_27940 deletion increased the susceptibility to aminoglycosides, tetracycline, tigecycline, erythromycin and fosfomycin. Excepting fosfomycin, the other antibiotics are inducers of the MexXY efflux pump. MexXY induction is required for P. aeruginosa resistance to these antibiotics, which is post-transcriptionally regulated by the anti-repressor ArmZ. Although mexXY is inducible by tobramycin in ΔPA14_27940, the induction level is lower than in the parental PA14 strain. Additionally, armZ is induced by tobramycin in PA14 and not in ΔPA14_27940, supporting that ΔPA14_27940 presents an ArmZ-mediated defect in mexXY induction. For its part, hypersusceptibility to fosfomycin may be due to a reduced expression of nagZ and agmK, which encode enzymes of the peptidoglycan recycling pathway. ΔPA14_27940 also presents defects in motility, an element with relevance in P. aeruginosa's virulence. Overall, our results support that PA14_27940 is a good target for the search of adjuvants that will increase the activity of antibiotics and reduce the virulence of P. aeruginosa.

Intra-Observer and Inter-Observer Reliability of Ankle Circumference Measurement in Patients with Diabetic Foot: A Prospective Observational Study.

Inflammation, being a typical response to vascular tissue alterations, induces variations in tissue oxygen diffusion pressure. Diabetic microangiopathy, an inflammatory process, is characterized by an increase in vascular flow at rest, reduced venous and arteriolar responses, and increased capillary permeability, resulting in oedema development, decreased transcutaneous oxygen pressure, and increased transcutaneous carbon dioxide pressure. This phenomenon potentially hampers ulcer healing. Although the figure-of-eight method has proven to be a reliable, valid, quick, and efficient test for assessing foot and ankle measurements in patients with oedema and compromised skin integrity, it has not been studied in patients with diabetic foot. The aim of this study was to determine and compare the intra- and inter-observer variabilities of the figure-of-eight method in patients with diabetic foot. A prospective observational and cross-sectional study was undertaken, involving sixty-one subjects from a specialized Diabetic Foot Unit. Three investigators with varying levels of experience independently measured the subjects to assess both intra-observer and inter-observer variability. The evaluation was conducted using the Intraclass Correlation Coefficient (ICC). In the statistical analysis, an ICC of 0.93, adjusted using a 95% confidence interval (CI), was obtained for inter-observer reliability ICC, indicating excellent reliability among observers. Furthermore, an ICC of 0.98 with a 95% CI was obtained for the intra-observer reliability analysis, indicating excellent reliability. The results support using this test during the clinical management of oedema in patients with diabetic foot. The absence of an objective, fast, and readily available diagnostic method for oedema in diabetic foot patients in clinical practice might pose a limitation. Subsequent research should tackle this issue and explore the correlation between ankle perimeter measurements and other clinical outcomes in diabetic foot patients, including wound healing and quality of life.