Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.

Metal and semimetal loadings in sediments and water from mangrove ecosystems: A preliminary assessment of anthropogenic enrichment in São Tomé island (central Africa).

Mangroves act as buffer areas for marine systems, providing a barrier to contamination from continental sources by retaining metal pollutants. This study evaluates metal and semimetal contamination in the water column and sediments of four mangroves located on the volcanic island of São Tomé. Several metals had a widespread distribution, with occasional high concentrations, linked to potential sources of contamination. However, the two smaller mangroves, located in the northern part of the island, tended to have high metal concentrations. Arsenic and chromium concentrations were notably concerning, particularly if we consider this is an isolated and non-industrialized island. This work highlights the need for further assessments and a better understanding of processes and implications of metal contamination in mangroves. This assumes a particular relevance in areas that have specific geochemical compositions (i.e., volcanic origin) and in developing countries, where people often rely directly and heavily on resources obtained from these ecosystems.

An innovative universal protocol for orthognathic surgery three-dimensional virtual simulation.

The aim of this technical note is to describe a protocol for three-dimensional virtual simulation of orthognathic surgery that has been designed to be easily implemented, without the need for any special clinical apparatus, software brand, or computed tomography sequence. The protocol comprises innovative concepts and simplified steps for image segmentation, creation of a composite skull, control of the condylar position, and sequencing of bimaxillary surgery. This protocol was applied by the developers in about 2000 cases performed between 2015 and 2022, and has become quite popular among local surgeons. Previous preliminary studies have shown that it meets the accuracy standards for clinical use, although further studies with larger numbers of patients are desirable for additional validation.

Electrochemical determination of several biofuel antioxidants in biodiesel and biokerosene using polylactic acid loaded with carbon black within 3D-printed devices.

Low oxidation stability is the main drawback of biodiesels and biokerosenes that is overcome by using antioxidants, which can be combined due to synergistic effects. This paper demonstrates that 3D-printed electrochemical devices can be applied to biofuel electroanalysis, including the monitoring of oxidation stability by quantifying the antioxidant content in biofuels. Fabrication requires 3D-printed acrylic templates at which a polylactic acid (PLA) filament with conducting carbon-black filling sensors is extruded by a 3D pen. The antioxidants butyl hydroxyanisole (BHA) and tert-butylhydroquinone (TBHQ) are the most employed additives in biodiesel production, and thus, their electrochemical behavior was investigated; 2,6-ditertbutylphenol (2,6-DTBP) was included in this investigation because it is commonly added to biokerosenes. The electrochemical surface treatment of the 3D-printed electrodes improved the current responses of all antioxidants; however, the electrochemical oxidation of TBHQ was clearly more affected by an electrocatalytic action shifting its oxidation towards less positive potentials (~200 mV), which resulted in a better separation of TBHQ and BHA oxidation peaks (+0.4 and +0.6 V vs Ag|AgCl, respectively). The oxidation of 2,6-DTBP occurred at more positive potentials (+1.2 V vs Ag|AgCl). The simultaneous determination of TBHQ and BHA by differential-pulse voltammetry resulted in linear responses in the range 0.5 and 175 µmol L-1 with limits of detection and quantification of 0.15 µmol L-1 and 0.5 µmol L-1, respectively. The presence of Fe3+, Cu2+, Pb2+, Mn2+, Cd2+, and Zn2+, even in high concentrations, did not interfere in the determination of TBHQ and BHA. The determination of 2,6-DTBP in biokerosene was achieved by cyclic voltammetry. All relative standard deviations (RSD) were lower than 6.0 %, indicating adequate precision of the methods. Spiked biofuel samples were analyzed (after dilution in electrolyte) and recovery values between 85 and 120% were obtained, which indicates absence of sample matrix effects.

Importance of Footwear Outsole Rigidity in Improving Spatiotemporal Parameters in Patients with Diabetes and Previous Forefoot Ulcerations.

We aimed to identify if any differences existed in spatiotemporal parameters during gait among different densities of rocker soles in patients with a history of neuropathic ulcerations and the differences in comfort between shoe conditions. This study was a cross-sectional study of 24 patients with diabetes and a history of neuropathic diabetic foot ulcers (DFUs). Spatiotemporal parameters (duration of stance phase (ms), stride length (cm), and step velocity (m/s)) were analyzed in barefoot, semirigid outsole, and rigid outsole footwear conditions. A dynamic pressure measurement system (Footscan® system, RSscan International, Belgium) was used to assess shoe conditions. We also analyzed differences in comfort between the shoe conditions using a visual analog scale. A Wilcoxon test for paired samples was used to assess gait differences. Result showed that a rigid outsole causes changes in the subphases of the stance phase (p < 0.001; Cohen d = 0.6) compared to a semirigid outsole. Stride length (p < 0.001; Cohen d = 0.66) and step velocity were significantly longer (p < 0.001; Cohen d = 2.03) with the use of rigid outsole footwear. A rigid rocker sole reduces the time of the stance phase, in addition to increasing the stride length and velocity of step in patients with a previous history of DFUs.

Additive-manufactured sensors for biofuel analysis: copper determination in bioethanol using a 3D-printed carbon black/polylactic electrode.

We show that fused deposition modelling (FDM) 3D-printed electrodes can be used for quality control of fuel bioethanol. 3D-printing using carbon black/polylactic acid (CB-PLA) filaments resulted in conductive and biodegradable electrodes for biofuel analysis. As a proof-of-concept, copper determination in fuel bioethanol was performed, as such ions catalyse oxidation processes during storage and transport. Square-wave anodic-stripping voltammetry (SWASV) of copper was achieved after sample dilution in 0.1 mol L-1 HCl as supporting electrolyte (resulting in 30:70% v/v ethanol:water). The linear responses were in the range between 10 and 300 µg L-1 (R = 0.999), inter-day precision was lower than 8% (n = 10, for 20 µg L-1) and limits of detection (LOD) and quantification (LOQ) using 180 s as deposition time were 0.097 µg L-1 and 0.323 µg L-1, respectively. Recovery values between 95 and 103% for the analysis of bioethanol spiked with known amounts of copper were obtained. These results show great promise of the application of 3D-printed sensors for the quality control of biofuels. Graphical abstract.

Predictors of Diabetic Foot Reulceration beneath the Hallux.

AIMS: To evaluate the factors that predict reulceration beneath the hallux in people with a history of diabetic foot ulceration. METHODS: A prospective study conducted between January 2012 and December 2014 was performed in a diabetic foot unit to assess the risk factors associated with hallux reulceration. Sixty patients with diabetic neuropathy and a history of previous ulcer were consecutively included. Sociodemographic factors and comorbidities plus the biomechanical and radiographic factors were obtained. Follow-up on participants was conducted every month, and they wore offloading therapeutic footwear and custom-made insoles. Hallux reulceration during the follow-up period was assessed as the main outcome measure in the study. RESULTS: Patients were followed up during 29 (14.2-64.4) months. Twenty-nine patients (52%) developed a new ulceration: 9 patients (31%) in the hallux and 20 (69%) in other locations. Functional hallux limitus (p = 0.005, 95% CI (2.097-73.128), HR 12.384) and increased body mass index (p = 0.044, 95% CI (1.003-1.272), HR 1.129) were associated with the hallux ulceration-free survival time in the multivariate Cox model. CONCLUSIONS: Obesity and the presence of functional hallux limitus increase the probability of developing hallux reulceration in patients with diabetic neuropathy and a history of ulcers.

Negative cross-resistance between structurally different Bacillus thuringiensis toxins may favor resistance management of soybean looper in transgenic Bt cultivars.

High adoption rates of single-gene Bacillus thuringiensis (Bt) Cry1Ac soybean impose selection pressure for resistance in the soybean looper, Chrysodeixis includens, a major defoliator in soybean and cotton crops. To anticipate and characterize resistance profiles that can evolve, soybean looper larvae collected from field crops in Brazil in 2013 were selected for resistance to Cry1Ac. Using two methods of selection viz., chronic exposure to Cry1Ac cotton leaves and the seven-day larval exposure to purified Cry1Ac on the artificial diet, 31 and 127-fold resistance was obtained in 11 and 6 generations of selection, respectively. The resistance trait had realized heritability of 0.66 and 0.72, respectively, indicating that most of the phenotypic variation in Cry1Ac susceptibility of the soybean looper larvae was due to additive genetic variation. The Cry1Ac-selected populations showed positive cross-resistance to Cry1Ab (6.7-8.7 fold), likely because these Bt toxins have a very similar molecular structure. Importantly, the Cry1Ac-selected populations became more susceptible to Cry2Aa and Cry1Fa, showing negative cross-resistance (up to 6-fold, P < 0.05). These results indicate that Cry1Ac, Cry1Fa, and Cry2A are compatible in a multi-toxin approach to minimize the risk of rapid adaptation of the soybean looper to Bt toxins.

Concurrent chemoradiation for locally advanced stage III non-small cell lung cancer with cisplatin, vinorelbine, and thoracic radiotherapy: a phase II study from the Galician Lung Cancer Group.

PURPOSE: The aim of this phase II study was to evaluate the activity and safety of the combination of cisplatin and vinorelbine with thoracic radiotherapy in unresectable locally advanced stage III non-small cell lung cancer (NSCLC). The primary endpoint was the objective response rate (ORR). Secondary objectives included toxicity profile, progression-free survival (PFS), and overall survival (OS). MATERIALS AND METHODS: A total of 48 NSCLC patients were enrolled (median age 60 years, 52% stage IIIA and 48% stage IIIB, 52% adenocarcinoma). Patients received three cycles of chemotherapy every 21 days [intravenous cisplatin 80 mg/m2 and intravenous vinorelbine 25 mg/m2 on day 1 and oral vinorelbine on day 8 (60 mg/m2)] concurrent with radiotherapy (66 Gy, administered at 1.8 Gy per day, five consecutive days per week). RESULTS: ORR was 79.2% (72.9% showing partial response and 6.3% showing complete response). With a median follow-up of 20.7 months, median PFS was 12 months and median OS was 36 months. Grade 3/4 toxicities were: neutropenia (14.5%), anaemia (6.2%), vomiting (2%), and oesophagitis (4.2%). No toxic deaths were reported. CONCLUSION: This combined regimen shows efficacy and a manageable safety profile. PFS and OS outcomes are encouraging and warrant further research.

Forefoot ulcer risk is associated with foot type in patients with diabetes and neuropathy.

AIMS: To stratify the ulceration risk according to the foot morphology in people with diabetes and a history of forefoot neuropathic ulceration. METHODS: A cross-sectional study was performed on 139 neuropathic individuals with diabetes and previous forefoot ulcers between January 2012 and February 2014. Foot position of the participants was evaluated by using the foot-posture index. A multivariate analysis adjusted for confounding variables was performed with the ulceration risk factors that were found in the univariate analysis. RESULTS: Two hundred and fifty-eight feet were analysed, 104 (40.3%) feet had a history of ulceration on the forefoot and 154 (59.7%) feet had no previous ulceration. Two positive tests of neuropathy (p<0.001; CI[1.961-6.249] OR 3.500), presence of deformities (p=0.043; CI[1.020-3.599] OR 1.916) and foot type (p=0.039) showed an association with ulceration risk in multivariate analyses. Pronated feet showed a higher risk of ulceration than supinated feet (p=0.011; CI[1.253-5.708] OR 2.675), while significant differences between neutral and supinated feet were not found (p=0.221; CI[0.719-2.753] OR 1.476). CONCLUSIONS: A pronated foot has a higher risk of ulceration on the forefoot in neuropathic people with deformities and diabetes mellitus. Foot type should be evaluated in people at risk of ulceration.

Control of Bovine Brucellosis from Persistently Infected Holdings Using RB51 Vaccination with Test-and-Slaughter: A Comparative Case Report from a High Incidence Area in Portugal.

Bovine brucellosis due to Brucella abortus infection causes significant reproductive and production losses in cattle and is a major zoonosis. Eradication of this disease has proved difficult to achieve in Portugal where it still occurs in some regions despite an ongoing national eradication programme. In 2004, the Alentejo region, a major cattle producing area, reported one of the highest levels of bovine brucellosis in the country, especially in one divisional area. In that area, bovine brucellosis was particularly problematic in a holding of ten herds, the largest extensive cattle unit in the country, which remained infected despite an extensive test-and-slaughter programme and depopulation of five herds. A 5-year programme of RB51 vaccination with biannual test-and-slaughter was thus implemented in 2004. The apparent animal seroprevalence decreased from 19% (646/3,400) to 3% (88/2930) on the third herd-level test and remained below 0.8% (27/3324) after the fourth test. After the tenth test, the holding had a prevalence of 0.1% (2/2332) and only one herd remained positive with a within-herd prevalence of 1.1% (2/177). The results were compared to all other herds (n = 10) in the divisional area that were also persistently infected but were subject only to test-and-slaughter before being depopulated. In these herds, the strategy of test-and-slaughter did not reduce the prevalence, which remained significantly higher than the vaccinated group (median = 0.48% and 8.5% in vaccinated versus non-vaccinated herds; Wilcoxon rank sum test; P < 0.01). The success of this pilot programme in continental Portugal provided a valuable case study to the official veterinary services by illustrating the value of RB51 vaccination with parallel testing and improved biosecurity as a comprehensive and sustainable strategy for bovine brucellosis control in persistently infected herds.

Preheating impact on the degree of conversion and water sorption/solubility of selected single-bottle adhesive systems.

OBJECTIVE: This study evaluated the degree of conversion (DC) and the water sorption/solubility of preheated single-bottle adhesive systems. METHODS AND MATERIALS: Five adhesive systems were tested: Adper Easy One and Adper Single Bond 2 (3M ESPE), Excite and Tetric N-Bond (Ivoclar/Vivadent), and XP Bond (Dentsply/Caulk). After storage for two hours at 25°C or 60°C, 50 samples (n=5) were prepared for all adhesive systems and stored dry in lightproof containers at 37°C for 24 hours. Fourier transform infrared/attenuated total reflectance spectroscopy was used to evaluate the DC, and water sorption/solubility was measured by means of mass loss and gain after water storage. The data were analyzed by two-way analysis of variance followed by Tukey's test (p<0.05). RESULTS: Preheated adhesive systems showed statistically significantly higher DC than those kept at 25°C. Except for XP Bond, preheated adhesive systems presented statistically significantly lower water sorption/solubility means. CONCLUSIONS: Preheating improved the DC for all tested adhesive systems. Also, it promoted a decrease of water sorption/solubility, except for the XP Bond adhesive system.

Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo.

As significant numbers of acute myeloid leukemia (AML) patients are still refractory to conventional therapies or experience relapse, immunotherapy using T cells expressing chimeric antigen receptors (CARs) might represent a valid treatment option. AML cells frequently overexpress the myeloid antigens CD33 and CD123, for which specific CARs can be generated. However, CD33 is also expressed on normal hematopoietic stem/progenitor cells (HSPCs), and its targeting could potentially impair normal hematopoiesis. In contrast, CD123 is widely expressed by AML, while low expression is detected on HSPCs, making it a much more attractive target. In this study we describe the in vivo efficacy and safety of using cytokine-induced killer (CIK) cells genetically modified to express anti-CD33 or anti-CD123 CAR to target AML. We show that both these modified T cells are very efficient in reducing leukemia burden in vivo, but only the anti-CD123 CAR has limited killing on normal HSPCs, thus making it a very attractive immunotherapeutic tool for AML treatment.

A phase II trial of erlotinib as maintenance treatment after concurrent chemoradiotherapy in stage III non-small-cell lung cancer (NSCLC): a Galician Lung Cancer Group (GGCP) study.

PURPOSE: This single arm, phase II study aims to evaluate the role of epidermal growth factor receptor-tyrosine-kinase inhibitor erlotinib as maintenance therapy following concurrent chemoradiotherapy (cCRT) in unresectable locally advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage IIIA o dry IIIB NSCLC with no evidence of tumor progression after receiving a standard cCRT regimen with curative intent were included. Oral erlotinib 150 mg/day was administered within 4-6 weeks after the end of the cCRT for a maximum of 6 months if no disease progression or intolerable toxicity occurred. Primary end point was the progression-free rate (PFR) at 6 months. Secondary end points included time to progression (TTP) and overall survival (OS). RESULTS: Sixty-six patients were enrolled and received maintenance treatment with erlotinib [average: 4.5 months (95 % CI 4.0-5.0)]. PFR at 6 months was 63.5 % (41/66). With a median follow-up of 22.7 months (95 % CI 13.5-37.1), the median TTP was 9.9 months (95 % CI 6.2-12.1), and the median OS was 24.0 months (95 % CI 17.3-48.6). Most common adverse events (AEs) related to erlotinib were rash (78.8 %; 16.7 % grade 3), diarrhea (28.8 %; 1.5 % grade 3), fatigue (15.2 %; 1.5 % grade 3), anorexia (7.6 %; 1.5 % grade 3) and vomiting (4.6 %; none grade 3). Five patients (7.6 %) were withdrawn due to AEs. CONCLUSIONS: Erlotinib as maintenance therapy is an active treatment after cCRT in unselected patients with stage III NSCLC, reaching a 6-month PFR of 63.5 % and a median OS of 24 months. The safety profile of maintenance erlotinib was as expected and manageable.

Tratamiento de úlceras infectadas de pie diabético. Efectividad clínica de un apósito de fibra de alginato e hidrocoloide, con plata. Análisis de resultados de una serie de casos / Treatment of infected diabetic foot ulcers clinical effectiveness of a dressing of alginate and hydrocolloid, with silver fiber. Analysis of results of a series of cases

Introducción. Niveles altos de carga bacteriana han demostrado una influencia negativa en la cicatrización de las úlceras. El uso de apósitos antimicrobianos con plata puede controlar el nivel de carga bacteriana de las heridas. El objetivo de este estudio fue evaluar la respuesta terapéutica de un apósito de fibra de alginato e hidrocoloide, con plata, en úlceras infectadas de pie diabético. Material y métodos. Se analizó una serie de casos de 6 pacientes con úlceras de pie diabético, sin enfermedad vascular periférica y diagnosticadas de colonización crítica y/o infección local mediante la recogida de signos clínicos inflamatorios. Los pacientes fueron tratados durante un período mínimo de 2 semanas. Se analizó el porcentaje de reducción del área de la úlcera desde el día de la inclusión hasta la retirada del apósito antimicrobiano. Resultados. El tratamiento tuvo una mediana de 5 semanas con una duración mínima de 2 y máxima de 6. La mediana del porcentaje de reducción de la superficie de las heridas fue de 47,7% (rango: 0,5%-90%). La media del porcentaje de reducción de la lesión a las 2 semanas fue del 58% y a la tercera semana del 67,14%. Todos los pacientes habían disminuido sus dimensiones a las 3 semanas de tratamiento de forma significativa (p<0,05). Conclusión. El uso de un apósito de fibra de alginato e hidrocoloide, con plata, favorece la cicatrización de las úlceras de pie diabético con infección local, reduciendo los signos clínicos inflamatorios de forma significativa en un período de 3 semanas (AU)

Introduction: High levels of bacterial load have shown a deleterious influence on wound healing. Using antimicrobial dressings can control ulcers’ bioburden. The aim of our study was to evaluate the improving of infected diabetic foot ulcers due an alginate’s fiber and hydrocolloid silver dressing. Material and Methods: We analysed a case series of 6 patients with diabetic foot ulcers without peripheral vascular disease and diagnosed from critical colonization and / or local infection according the presence of inflammation clinical signs. Patients were treated for a minimum period of two weeks. We analysed the percentage reduction in ulcer area from the day of enrolment to antimicrobial dressing removal. Results: The duration of treatment had a median of 5 weeks with a minimum of 2 weeks and up to 6. The median percentage of area reduction of the wounds was 47.7% (range: 0.5%-90%). The mean percentage reduction on the lesion was 58% from 2 weeks and 67.14% at 3 weeks. All patients had reduced significantly their size at 3 weeks from beginning of treatment (p<0.05). Conclusion: The use of an alginate’s fiber and hydrocolloid silver dressing promotes healing on diabetic foot ulcers with local infection, reducing the inflammatory clinical signs significantly over a period of three weeks (AU)

Classification of hospital pathways in the management of cancer: application to lung cancer in the region of burgundy.

CONTEXT: The evaluation of national cancer plans is an important aspect of their implementation. For this evaluation, the principal actors in the field (doctors, nurses, etc.) as well as decision-makers must have access to information that is reliable, synthetic and easy to interpret, and which reflects the implementation process in the field. We propose here a methodology to make this type of information available in the context of reducing inequalities with regard to access to healthcare for patients with lung cancer in the region of Burgundy. METHODS: We used the national medico-administrative DRG-type database, which gathers together all hospital stays. By using this database, it was possible to identify and reconstruct the care management history of these patients. That is, by linking together all attended hospitals, sorted chronologically. Eligible patients were at least 18 years old, whatever the gender and had undergone surgery for their lung cancer. They had to be residents of Burgundy at the time of the first operation between 2006 and 2008. Patient's pathway was defined as the sequence of all attended hospitals (hospital stays) during the year of follow up linked together using an anonymised patient identifier. We then constructed a pathway typology of pathway using an unsupervised clustering method, and conducted a spatial analysis of this typology. RESULTS: Between 2006 and 2008, we selected 495 patients in the 4 administrative departments of the Burgundy region. They accounted for a total of 3821 stays during the year of follow-up. There were 393 men (79%) and the mean age was 64 (95% confidence interval: 63-65) years. We reconstructed 94 pathways (about five per patient). Here, neighbourhood's cares accounted for 41% of them, while 44% included a surgical intervention outside the region of Burgundy. We constructed a pathway typology with five classes. Spatial analysis showed that the vast majority of initial surgeries took place in the major regional centres. CONCLUSION: The construction of a pathway typology leads to better understanding of the reasoning that lies behind the movements of patients. It opens the way for analysis of the collaboration between the different healthcares establishments attended, which should bring to light associations that need to be developed.

Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor

We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC (AU)