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Objective: The goal of this systematic review was to identify the mechanisms associated with the enzymatic degradation of collagen and gelatin biomaterials and the possible associated flaws. Methods: Four databases (PubMed, B-On, Cochrane Library, and ResearchGate) were used for the bibliographic search of articles. The research question was formulated using the PCC method, (P): collagen or gelatin sponges, hydrogels, and scaffolds; concept (C): enzymatic degradation of collagen or gelatin sponges, hydrogels, and scaffolds; and context (C): effect of enzymatic action on degradation time of collagen or gelatin sponges, hydrogels, and scaffolds. The search was contextualized according to PRISMA recommendations. The identification and exclusion of evidence followed the PRISMA criteria, with specific inclusion and exclusion factors being stipulated for the selection of articles. The risk of bias assessment was performed using the QUIN Scale. Results: The initial search was composed of 13,830 articles after removing duplicates; 56 articles followed for the full-text reading; 45 were excluded; then, 11 articles were obtained, constituting the results of this systematic review. All studies evaluated the materials using gravimetric analysis, and collagenases were the proteases used for the degradation solution. The materials tested were as follows: human-like collagen (HLC) hydrogel with microbial transglutaminase (MTGase), gelatin sponges subjected to different types of crosslinking, and collagen scaffolds with different types of crosslinking. The period of analysis varied between 0.25 h and 35 days. It was possible to highlight the lack of uniformity in the protocols used, which varied largely, thus influencing the degradation times. The risk of bias was low in nine studies and medium in two studies. Conclusions: This systematic review identified a gap in the literature, highlighting the absence of in vitro studies using human saliva and a collagenase concentration close to the physiological levels to simulate oral dynamics. However, based on existing literature, the mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials were comprehensively understood, answering the first research question postulated. In response to the second research question, the main shortcomings identified in the laboratory evaluation of mechanisms associated with collagen enzymatic degradation in collagen and gelatin biomaterials included the lack of standardization in degradation test protocols; this limited inter-study comparisons, which increased heterogeneity. Additionally, variations in collagenase concentrations and types influenced collagen degradation rates, and inappropriate evaluation intervals hindered the identification of total degradation time.

In 1858 a series of essays titled Manly Health and Training made their appearance in the New York Atlas, written by Walt Whitman under the penname of Mose Velsor. The professed goal was to discuss suggestions and ideas to improve the general physical condition of its readers. Whitman regarded this as a necessary condition to match America’s democratic character. Indeed, from reading his guide we can see how for him the health of the body politic is dependent on the health and physical vigour of its citizens. In typical Whitman fashion, the essays address a multitude of topics other than the usual issues expected of a fitness manual. Besides the customary issues of diet and exercise, he also talks politics, morality, the weather, longevity, Greek athleticism, hygiene habits. This article will focus on Whitman’s thoughts about the physical standards he believed the American people ought to meet to sustain American democracy, link this with Whitman’s view of Ulysses Grant as an example of the ‘ideal’ American citizen and also venture why he was so understanding towards the latter during his troubled presidency.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

This systematic review aims to assess the impact of high (>30 Hz) and low (≤30 Hz) frequency vibrations on orthodontic tooth movement (OTM). Several articles were collected through a systematic search in the databases MEDLINE and SCOPUS, following PRISMA methodology and using a PICO question. Relevant information on selected articles was extracted, and the quality of each study was assessed by the quality assessment tools EPHPP, ROBINS-1 and STAIR. Out of 350 articles, 30 were chosen. Low-frequency vibrations did not seem to accelerate OTM with aligners or fixed appliances, despite some positive outcomes in certain studies. Conversely, high-frequency vibrations were linked to increased aligner change, tooth movement, and space closure with fixed appliances. In vivo studies reported favourable results with high-frequency vibrations (60 Hz to 120 Hz), which stimulate bone biomarkers, facilitating alveolar bone remodelling. The results suggest that high-frequency vibration effectively speeds up orthodontic tooth movement, showing promise in both in vivo and clinical studies. Larger-scale research is needed to strengthen its potential in orthodontics.

Peripheral nerve injuries (PNI) impact millions of individuals in the United States, prompting thousands of nerve repair procedures annually. Nerve conduits (NC) are commonly utilized to treat nerve injuries under 3 cm but larger gaps still pose a challenge for successful peripheral nerve regeneration (PNR) and functional recovery. This is partly attributed to the absence of bioactive agents such as stem cells or growth factors in FDA-approved conduits due to safety, harvesting, and reproducibility concerns. Therefore, curcumin, a bioactive phytochemical, has emerged as a promising alternative bioactive agent due to its ability to enhance PNR and overcome said challenges. However, its hydrophobicity and rapid degradation in aqueous solutions are considerable limitations. In this work, a nanoscale delivery platform with tannic acid (TA) and polyvinylpyrrolidone (PVP) was developed to encapsulate curcumin for increased colloidal and chemical stability. The curcumin nanoparticles (CurNPs) demonstrate significantly improved stability in water, reduced degradation rates, and controlled release kinetics when compared to free curcumin. Further, cell studies show that the CurNP is biocompatible when introduced to neuronal cells (SH-SY5Y), rat Schwann cells (RSC-S16), and murine macrophages (J774 A.1) at 5 μM, 5 μM, and 10 μM of curcumin, respectively. As a result of these improved physicochemical properties, confocal fluorescence microscopy revealed superior delivery of curcumin into these cells when in the form of CurNPs compared to its free form. A hydrogen peroxide-based oxidative stress study also demonstrated the CurNP’s potential to protect J774 A.1 cells against excessive oxidative stress. Overall, this study provides evidence for the suitability of CurNPs to be used as a bioactive agent in NC applications.

With the increasing incidence of diverse global bacterial outbreaks, it is important to build an immutable decentralized database that can capture regional changes in bacterial resistance with time. Herein, we investigate the use of a rapid 3D printed µbiochamber with a laser-ablated interdigitated electrode developed for biofilm analysis of Pseudomonas aeruginosa, Acinetobacter baumannii and Bacillus subtilis using electrochemical biological impedance spectroscopy (EBIS) across a 48 h spectrum, along with novel ladder-based minimum inhibitory concentration (MIC) stencil tests against oxytetracycline, kanamycin, penicillin G and streptomycin. Furthermore, in this investigation, a search query database has been built demonstrating the deterministic nature of the bacterial strains with real and imaginary impedance, phase, and capacitance, showing increased bacterial specification selectivity in the 9772.37 Hz range.

Small and medium enterprises (SMEs) are responsible for 90% of all business and 50% of employment globally, mostly female jobs. Therefore, measuring SMEs’ performance under the digital transformation (DT) through methods that encompass sustainability represents an essential tool for reducing poverty and gender inequality (United Nations Sustainable Development Goals). We aimed to describe and analyze the state-of-art performance evaluations of digital transformation in SMEs, mainly focusing on performance measurement. Also, we aimed to determine whether the tools encompass the three pillars of sustainability (environmental, social, and economic). Through a systematic literature review (SLR), a search on Web of Science (WoS) and Scopus resulted in the acceptance of 74 peer-reviewed papers published until December 2021. Additionally, a bibliometrics investigation was executed. Although there was no time restriction, the oldest paper was published in 2016, indicating that DT is a new research topic with increasing interest. Italy, China, and Finland are the countries that have the most published on the theme. Based on the results, a conceptual framework is proposed. Also, two future research directions are presented and discussed, one for theoretical and another for practical research. Among the theoretical development, it is essential to work on a widely accepted SME definition. Among the practical research, nine directions are identified–e.g., applying big data, sectorial and regional prioritization, cross-temporal investigations etc. Researchers can follow the presented avenues and roads to guide their researchers toward the most relevant topics with the most urgent necessity of investigation.

Introduction: Actinic keratoses (AKs) are common skin lesions that arise in skin areas chronically exposed to ultraviolet (UV) radiation. They may progress to squamous cell carcinomas in 16% of cases within 1 year. Clinically, they present as erythematous scaly plaques and mainly affect face, neck, chest, back of the hands, shoulders and scalp. Cumulative exposure to UV radiation is the main risk factor. Other factors are advanced age, outdoor activities, geographic characteristics, exposure to artificial UV radiation and chronic skin inflammation. Many of these factors are often present in rural populations where agriculture remains important.Methods/Results: This presentation present the case of a 67-year-old male patient, who went to his Family Doctor for odynophagia with 2 days of evolution. He had hypertrophied and erythematous tonsils with purulent exudate and was medicated with amoxicillin-clavulanic acid 875+125 mg for 8 days with improvement of symptoms. To perform the observation of the oropharynx, he was asked to remove his face mask, which revealed an erythematous scaly lesion in the left malar region, suggestive of actinic keratosis. He was referred to Dermatology where cryotherapy of the lesion was performed with a favourable evolution without relapses.Discussion: AKs are pre-malignant lesions. Rural populations are particularly at risk for their development. It is therefore essential to raise awareness for the use of protective measures as well as to investigate lesions already established. This case seeks to alert for the fact that the use of masks due to COVID-19 pandemic can hide pre-malignant lesions of the face with a consequent delay in diagnosis and treatment.

Chronic skin wound is a chronic illness that possesses a risk of infection and sepsis. In particular, infections associated with antibiotic-resistant bacterial strains are challenging to treat. To combat this challenge, a suitable alternative that is complementary to antibiotics is desired for wound healing. In this work, we report multi-functional nanoscale chitosan vesicles loaded with manganese (Chi-Mn) that has potential to serve as a new tool to augment traditional antibiotic treatment for skin wound healing. Chi-Mn showed antioxidant activity increase over time as well as antimicrobial activity against E. coli and P. aeruginosa PA01. The modified motility assay that mimicked a skin wound before bacterial colonization showed inhibition of bacterial growth with Chi-Mn treatment at a low area density of 0.04 µg of Mn per cm2. Furthermore, this study demonstrated the compatibility of Chi-Mn with a commercial antibiotic showing no loss of antimicrobial potency. In vitro cytotoxicity of Chi-Mn was assessed with macrophages and dermal cell lines (J774A.1 and HDF) elucidating biocompatibility at a wide range (2 ppm–256 ppm). A scratch wound assay involving human dermal fibroblast (HDF) cells was performed to assess any negative effect of Chi-Mn on cell migration. Confocal microscopy study confirmed that Chi-Mn tested at the MIC (16 ppm Mn) has no effect on cell migration with respect to control. Overall, this study demonstrated the potential of Chi-Mn nanovesicles for wound healing applications.

Summary: Background: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p

Este artículo analiza el concepto de destino turístico inteligente (DTI), examinando su relación con la sostenibilidad. En este nivel de los destinos turísticos, este trabajo indica las principales dimensiones que pueden ayudar a mejorar su competitividad (gobernanza, innovación, tecnología, accesibilidad y sostenibilidad). Nuestro artículo se centra principalmente en la sostenibilidad, indicando acciones e indicadores que se pueden utilizar en las diferentes dimensiones de la sostenibilidad (económica, ambiental y social) y que pueden ayudar a promover soluciones sostenibles en el sector turístico desde ese nivel de localización de los destinos turísticos. El artículo también examina la relación recíproca entre DTI y empresas turísticas con relación a la importancia de la gobernanza, la innovación, la tecnología y la accesibilidad para las empresas, enfatizando el papel de la sostenibilidad en destinos y empresas turísticas. Algunas recomendaciones metodológicas para estudios futuros son también indicadas.

Abstract. Background:. There are limited bladder-preserving therapeutic options for patients with high-risk non-muscle invasive bladder cancer (NMIBC) after failed Bacillus Calmette-Guérin (BCG) therapy. Salvage intravesical docetaxel therapy was described in 2006 but has not been validated outside of the original institution. In this study, we presented the first external report on the oncologic outcomes of intravesical docetaxel. Materials and methods:. We identified 13 patients with high-risk NMIBC treated with ≥1 course of intravesical BCG who received salvage intravesical docetaxel. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Associations of clinicopathologic features with RFS were evaluated using Cox regression. Results:. Median age was 75.2 years, and 46.2% of patients were male. Of the patients 92.3% had a prior diagnosis of high-grade T1 disease, 38.5% had a prior diagnosis of carcinoma in situ, and 46.2% had received ≥2 courses of BCG. Only 1 (7.7%) patient experienced docetaxel-related toxicity. Nine (69.2%) patients had a complete response at initial post-docetaxel cystoscopy. During a median follow-up of 12.0 (interquartile range 5.0–18.1) months, a total of 7 (53.8%) patients developed recurrence. Median time to recurrence was 10.1 (interquartile range 4.8–11.6) months. Estimated RFS at 6-, 12-, 18-, and 24-months was 75%, 50%, 50%, and 25%. Three (23.1%) patients ultimately underwent cystectomy. On univariable analysis, multiple courses of induction BCG were associated with decreased RFS, although this did not reach statistical significance (hazard ratio 4.69, p = 0.08). Conclusions:. In this first external validation study, intravesical docetaxel was associated with excellent response rates and intermediate-term RFS among patients with high-risk NMIBC after failed BCG therapy.

Bacterial spot of tomato is among the most economically relevant diseases affecting tomato plants globally. In previous studies, non-formulated magnesium oxide nanoparticles (nano-MgOs) significantly reduced the disease severity in greenhouse and field conditions. However, the aggregation of nano-MgO in liquid suspension makes it challenging to use in field applications. Therefore, we formulated two novel MgO nanomaterials (SgMg #3 and SgMg #2.5) and one MgOH2 nanomaterial (SgMc) and evaluated their physical characteristics, antibacterial properties, and disease reduction abilities. Among the three Mg nanomaterials, SgMc showed the highest efficacy against copper-tolerant strains of Xanthomonas perforans in vitro, and provided disease reduction in the greenhouse experiments compared with commercial Cu bactericide and an untreated control. However, SgMc was not consistently effective in field conditions. To determine the cause of its inconsistent efficacy in different environments, we monitored particle size, zeta potential, morphology, and crystallinity for all three formulated materials and nano-MgOs. The MgO particle size was determined by the scanning electron microscopy (SEM) and dynamic light scattering (DLS) techniques. An X-ray diffraction (XRD) study confirmed a change in the crystallinity of MgO from a periclase to an Mg(OH)2 brucite crystal structure. As a result, the bactericidal activity correlated with the high crystallinity present in nano-MgOs and SgMc, while the inconsistent antimicrobial potency of SgMg #3 and SgMg #2.5 might have been related to loss of crystallinity. Future studies are needed to determine which specific variables impair the performance of these nanomaterials in the field compared to under greenhouse conditions. Although SgMc did not lead to significant disease severity reduction in the field, it still has the potential to act as an alternative to Cu against bacterial spot disease in tomato transplant production.

There is increasing recognition that point-of-care ultrasound (POCUS), performed by the clinician at the bedside, can be a natural extension of the clinical examination—the modern abdominal “stethoscope” and provides an opportunity to expedite the care pathway for patients with acute gallbladder disease. The primary aims of this study were to benchmark the accuracy of surgeon-performed POCUS in suspected acute gallbladder disease against standard radiology or pathology reports and to compare time to POCUS diagnosis with time to definitive imaging. This prospective single-arm observational cohort study was conducted in four hospitals in Ireland, Italy, and Portugal to assess the accuracy of POCUS against standard radiology in patients with suspected acute biliary disease (ClinicalTrials.govIdentifier: NCT02682368). The findings of surgeon-performed POCUS were compared with those on definitive imaging or surgery. Of 100 patients recruited, 89 were suitable for comparative analysis, comparing POCUS with radiological findings in 84 patients and with surgical/histological findings in five. The overall global accuracy of POCUS was 88.7% (95% CI, 80.3–94.4%), with a sensitivity of 94.7% (95% CI, 85.3–98.9%), a specificity of 78.1% (95% CI, 60.03–90.7%), a positive likelihood ratio (LR+) of 4.33 and negative likelihood ratio (LR) of 0.07. The mean time from POCUS to the final radiological report was 11.9 h (range 0.06–54.9). In five patients admitted directly to surgery, the mean time between POCUS and incision was 2.30 h (range 1.5–5), which was significantly shorter than the mean time to formal radiology report. Sixteen patients were discharged from the emergency department, of whom nine did not need follow-up. Our study is one of the very few to demonstrate a high concordance between surgeon-performed POCUS of patients without a priori radiologic diagnosis of gallstone disease and shows that the expedited diagnosis afforded by POCUS can be reliably leveraged to deliver earlier definitive care for patients with acute gallbladder pathology, as the general surgeon skilled in POCUS is uniquely positioned to integrate it into their bedside assessment.

Diabetic foot ulcer morbidity and mortality are dramatically increasing worldwide, reinforcing the urgency to propose more effective interventions to treat such a devastating condition. Previously, using a diabetic mouse model, we demonstrated that administration of bone marrow mesenchymal stem cells derivatives is more effective than the use of bone marrow mesenchymal stem cells alone. Here, we used the aforementioned treatments on three patients with grade 2 diabetic foot ulcers and assessed their beneficial effects, relative to the conventional approach. In the present study, two doses of cell derivatives, one dose of mesenchymal stem cells or one dose of vehicle (saline solution with 5% of human albumin), were intradermally injected around wounds. Wound healing process and changes on re-epithelialization were macroscopically evaluated until complete closure of the ulcers. All ulcers were simultaneously treated with conventional treatment (PolyMen® dressing). Patients treated with either cell derivatives or mesenchymal stem cells achieved higher percentages of wound closure in shorter times, relative to the patient treated with the conventional treatment. The cell derivative and mesenchymal stem cells approaches resulted in complete wound closure and enhanced skin regeneration at some point between days 35 and 42, although no differences between these two treatments were observed. Moreover, wounds treated with the conventional treatment healed after 161 days. Intradermal administration of cell derivatives improved wound healing to a similar extent as mesenchymal stem cells. Thus, our results suggest that mesenchymal stem cell derivatives may serve as a novel and potential therapeutic approach to treat diabetic foot ulcers.

Plotter cutters in stencil mask prototyping are underutilized but have several advantages over traditional MEMS techniques. In this paper we investigate the use of a conventional plotter cutter as a highly effective benchtop tool for the rapid prototyping of stencil masks in the sub-250 μm range and characterize patterned layers of organic/inorganic materials. Furthermore, we show a new diagnostic monitoring application for use in healthcare, and a potential replacement of the Standard Kirby-Bauer Diffusion Antibiotic Resistance tests was developed and tested on both Escherichia coli and Xanthomonas alfalfae as pathogens with Oxytetracycline, Streptomycin and Kanamycin. We show that the reduction in area required for the minimum inhibitory concentration tests; allow for three times the number of tests to be performed within the same nutrient agar Petri dish, demonstrated both theoretically and experimentally resulting in correlations of R ≈ 0.96 and 0.985, respectively for both pathogens.

The study sought to know the factors that have contributed to the students of the academies to change the mats through the streets. To reach it, 10 male and 10 female runners were interviewed. The interviews were handled through the content analysis technique. The results revealed the composition of groups, the health discourse, the presence of competition and the culture of consumption as the factors that lead the students of academies to the practices of street races. Therefore, the study concluded that replacing mats on the streets is a multifactorial decision.

Abstract Background Timing and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted. Methods This worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018. Results A total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47 years (interquartile range [IQR] 28–66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6 days (IQR 4–10). Using multivariable logistic regression, independent variables associated with in-hospital mortality were identified: age > 80 years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate ≥ 22 breaths/min, systolic blood pressure < 100 mmHg, AVPU responsiveness scale (voice and unresponsive), blood oxygen saturation level (SpO2) < 90% in air, platelet count < 50,000 cells/mm3, and lactate > 4 mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0–1, 22.7% for those who had scores of 2–3, 46.8% for those who had scores of 4–5, and 86.7% for those who have scores of 7–8. Conclusions The simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.

Although most birds show karyotypes with diploid number (2n) around 80, with few macrochromosomes and many microchromosomes pairs, some groups, such as the Accipitriformes, are characterized by a large karyotypic reorganization, which resulted in complements with low diploid numbers, and a smaller number of microchromosomal pairs when compared to other birds. Among Accipitriformes, the Accipitridae family is the most diverse and includes, among other subfamilies, the subfamily Aquilinae, composed of medium to large sized species. The Black-Hawk-Eagle (Spizaetus tyrannus-STY), found in South America, is a member of this subfamily. Available chromosome data for this species includes only conventional staining. Hence, in order to provide additional information on karyotype evolution process within this group, we performed comparative chromosome painting between S. tyrannus and Gallus gallus (GGA). Our results revealed that at least 29 fission-fusion events occurred in the STY karyotype, based on homology with GGA. Fissions occurred mainly in syntenic groups homologous to GGA1-GGA5. On the other hand, the majority of the microchromosomes were found fused to other chromosomal elements in STY, indicating these rearrangements played an important role in the reduction of the 2n to 68. Comparison with hybridization pattern of the Japanese-Mountain-Eagle (Nisaetus nipalensis orientalis), the only Aquilinae analyzed by comparative chromosome painting previously, did not reveal any synapomorphy that could represent a chromosome signature to this subfamily. Therefore, conclusions about karyotype evolution in Aquilinae require additional painting studies.

Abstract Despite the richness of species in the Hirudinidae family, little is known about the genome organization of swallows. The Progne tapera species presents genetic and morphological difference when compared to other members of the same genus. Hence, the aims of this study were to analyze the chromosomal evolution of three species Progne tapera, Progne chalybea and Pygochelidon cyanoleuca - by comparative chromosome painting using two sets of probes, Gallus gallus and Zenaida auriculata, in order to determine chromosome homologies and the relationship between these species. All karyotypes exhibited 76 chromosomes with similar morphology, except for the 5th, 6th and 7th chromosome pairs in P. cyanoleuca. Additionally, comparative chromosome painting demonstrated the same hybridization pattern in the two Progne, which was similar to the putative avian ancestral karyotype, except for the centric fission in the first pair, as found in other Passeriformes. Thus, these data display a close relationship between the Progne species. Although P. cyanoleuca demonstrated the same fission in the first pair of the ancestral syntenic (GGA1), it also showed an additional chromosomal rearrangement for this species, namely a fusion with a microchromosome in the seventh pair.

Wildfires are complex natural events that cause significant environmental and property damage, as well as human losses, every year throughout the world. In order to aid in their management and mitigate their impact, efforts have been directed towards developing decision support systems that can predict wildfire propagation. Most of the available tools for wildfire spread prediction are based on the Rothermel model that, apart from being relatively complex and computing demanding, depends on several input parameters concerning the local fuels, wind or topography, which are difficult to obtain with a minimum resolution and degree of accuracy. These factors are leading causes for the deviations between the predicted fire propagation and the real fire propagation. In this sense, this paper conducts a literature review on optimization methodologies for wildfire spread prediction based on the use of evolutionary algorithms for input parameter set calibration. In the present literature review, it was observed that the current literature on wildfire spread prediction calibration is mostly focused on methodologies based on genetic algorithms (GAs). Inline with this trend, this paper presents an application of genetic algorithms for the calibration of a set of the Rothermel model’s input parameters, namely: surface-area-to-volume ratio, fuel bed depth, fuel moisture, and midflame wind speed. The GA was validated on 37 real datasets obtained through experimental prescribed fires in controlled conditions.

Introduction: Aggressive fluid therapy is frequently suggested in the treatment of acute pancreatitis. However, there is some controversy about the effect of this therapy concerning the development of clinical complications and the need for surgery. Objectives: To explore the relationship between fluid administration in the first 48 hours and the development of local or systemic complications, to contribute to clarifying some open questions on this subject. Methods: This study is based on records of 109 patients admitted to the Surgical High Dependency Unit of Tondela Viseu Hospital Centre, between 2007 and 2012, with the diagnosis of acute pancreatitis. Data were explored, and statistical tests were used to identify variables that differentiate patients with complications. Receiver operating characteristic (ROC) curves allowed to relate the amount of fluids at 48 hours with the occurrence of each complication. Logistic regression models were used to identify independent risk factors for each complication. Results: There was no significant relationship between fluid therapy at 48 hours with death nor with the occurrence of systemic complications. As opposed, fluid therapy at 48 hours revealed to be associated with local and late complications, presence of infection and need for surgery. Conclusion: High levels of fluid therapy in the first 48 hours were associated with the development of complications.

Abstract Background Combined antiretroviral therapy (cART) in HIV-infected patients has been associated with lipodystrophy, metabolic abnormalities, and an increased risk of cardiovascular disease. Ultrasound measures of carotid artery intima-media thickness (cIMT) have been used as a valid measure of subclinical atherosclerosis and as a tool to predict the risk of cardiovascular events. Our aim was to evaluate the progression of cIMT in HIV-infected patients subjected to cART, with and without lipodystrophy, over a one-year period. Methods We performed a one-year prospective cohort study to compare changes in cIMT, metabolic and inflammation markers in HIV-infected patients undergoing cART. Body composition was assessed by dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Levels of blood pressure, lipids and inflammatory markers were evaluated, as well as ultrasound measures of cIMT. Lipodystrophy defined by Fat Mass Ratio (L-FMR) is measured as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared, using the chi-square or Fisher’s exact test. Wilcoxon ranks tests and the McNemar chi-square tests were used to compare results of selected variables, from the first to the second year of evaluation. Means of cIMT, adjusted for age, glucose, triglycerides levels, systolic blood pressure (SBP), and waist to hip ratio were calculated, using generalised linear models for repeated measures. Results L-FMR was present in 44.3% of patients, and the mean of cIMT increased significantly in this group [0.82 (0.26) vs 0.92 (0.33); p = 0.037], as well as in patients without lipodystrophy [0.73 (0.20) vs 0.84 (0.30); p = 0.012]. In the overall sample, the progression of cIMT was statistically significant after the adjustment for age, glucose, triglycerides, and SBP, but the significance of the progression ceased after the adjustment for waist/hip ratio [0.770 (0.737–0.803) vs 0.874 (0.815–0.933); p = 0.514]. Conclusions Carotid IMT progressed significantly in both groups of this HIV-infected cohort, however no association between the progression of cIMT and the presence of lipodystrophy defined by FMR was found. Visceral adipose tissue had an impact on the increment of cIMT, both in patients with, and without lipodystrophy defined by FMR.

Wasting disease in small ruminants is frequently detected at slaughterhouses. The wasting disorder is manifested by the deterioration of the nutritional and physiological state of the animal indicated by thinness, emaciation, and cachexia. Evidence of emaciation and cachexia, alone, are pathological conditions leading to carcass condemnation during an inspection. Several diseases are associated with a wasting condition, including scrapie, pseudotuberculosis, tuberculosis, paratuberculosis, Maedi Visna, and tumor diseases. On the other hand, parasitic diseases, nutrition disorders, exposure or ingestion of toxins, metabolic conditions, inadequate nutrition due to poor teeth, or poor alimentary diet are conditions contributing to poor body condition. Classical and atypical scrapie is naturally occurring transmissible spongiform encephalopathies in small ruminants. The etiological agent for each one is prions. However, each of these scrapie types is epidemiologically, pathologically, and biochemically different. Though atypical scrapie occurs at low incidence, it is consistently prevalent in the small ruminant population. Hence, it is advisable to include differential diagnosis of this disease, from other possibilities, as a cause of wasting conditions detected during meat inspection at the abattoir. This manuscript is a review of the measures in force at the abattoir for scrapie control, focusing on the differential diagnosis of gross lesions related to wasting conditions detected in small ruminants during meat inspection.

Background. In emergency surgery, a very heterogeneous approach is required in the decision making process, especially when considering the patient’s postoperative quality of life as well as medical, ethical, and legal factors. In some cases, the presence of an Advance Directive (AD) form may potentially help resolve the surgeon’s dilemma. Objectives. The primary objective of this survey was to investigate the opinions of surgeons across a representative cross-section of European countries regarding the decision making process using a specific case scenario so as to identify similarities and differences in practice. A secondary objective was to identify the possibility of establishing a more uniform approach and best practice. Method. A survey was conducted of surgeons from a range of European countries. Questionnaires were designed to obtain an overview of decision making in relation to the Limitation of Therapeutic Effort (LTE) using a specific case study and the level of awareness and practical use of ADs. Surveys were distributed via email to the members of the ESTES (European Society for Trauma and Emergency Surgery) and AEC (Association of Spanish surgeons), with voluntary, anonymous participation. Conclusions. Clear and additional support in the form of legal and ethical guidance with clinical protocols for surgical practice in such case scenarios is necessary. Wider use of ADs, together with education about their role and support for patients and relatives, would benefit the type of patient described in our scenario. A multidisciplinary team should play a more active role in decision making in order to avoid surgical procedures that are potentially futile. The concepts of LTE and Quality of life need a broader understanding among surgeons as well as more consistent application.

Introduction: It is well known that musicians are a group prone to suffer from playing-related musculoskeletal disorders. Professional orchestra musicians play for several hours a week and have to fight against pain caused by their profession. The aim of this study was to explore and describe self-reported complaints among professional orchestra musicians and to compare its intensity and the prevalence between string and wind instruments. Material and Methods: Hundred and twelve professional orchestra musicians from the three main professional orchestras from the North of Portugal were individually interviewed about the prevalence and the intensity (measured by verbal numerical scale for pain) of their playing-related musculoskeletal disorders. Results: About two third (62.5%) of the interviewed musicians presented playing-related musculoskeletal disorders during the time of the interview. Despite there are no significant statistic values between groups, results suggested that playing-related musculoskeletal disorders are more common in string players and more intense in wind players. Discussion: Referring to the prevalence of playing-related musculoskeletal disorders, our data is in line with other studies from different countries. More than half of professional orchestra musicians in the North of Portugal are playing with a mild to moderate pain. Conclusion: Future studies focusing on working-related problems among professional orchestra musicians in Portugal would be useful to better describe the problem of occupational diseases among performing artist.

Abstract Nanocarriers for medical applications must work reliably within organisms, independent of the individual differences in the blood proteome. Variation in the blood proteome, such as immunoglobulin levels, is a result of environmental, nutrition, and constitution conditions. This variation, however, should not influence the behavior of nanocarriers in biological media. The composition of the protein corona is investigated to understand the influence varying immunoglobulin levels in the blood plasma have on the interactions with nanocarriers. Specifically, the composition of the nanocarriers' coronas is analyzed after incubation in plasma with normal or elevated immunoglobulin G (IgG) levels, and cellular uptake is monitored in cell lines containing different immunoglobulin receptors. Here, it is reported that upon doubling the IgG concentration in plasma, the IgG fraction in the protein corona increases by a factor of 40 independent of the nanocarrier material. This results in a significant increase in uptake in cells exhibiting IgG binding receptors. Furthermore, precoating nanocarriers with clusterin successfully prevents dominant IgG‐adsorption and additionally reduces cellular internalization, after incubation with IgG‐enriched plasma. Therefore, precoating nanocarriers may be utilized as a powerful method to reduce the influence of individual variations in blood composition on the protein corona.

The main purpose of this paper is to integrate the literature on human resource management (HRM) and environmental management. Moreover, the paper shows the role that green human resource management (GHRM) plays in environmental management activities. This article examines the main relationships between human resource management and environmental strategy, emphasizing reciprocal influences. Moreover, the main human resource practices used in the literature are examined. In addition, methodological approaches that can be appropriate to advance the study of the link between human resource management and environmental strategy are proposed. Ideas for future research are also provided. As the role of human capital in implementing environmental management is a mature field of research, a new topic known as green human resource management has emerged. We examine studies that analyze both the relationship between general human resource management and environmental strategy and between green human resource management and environmental strategy.

Objective: To demonstrate that acupuncture has an instant effect in equilibrating the imbalanced electrical conductivity of Yuan-Source acupoints after intervention on the Luo-Connecting acupoint (one-side) of the same channel.

Research examining privacy in a higher education setting tends to focus on the student perspective whilst largely overlooking the academic perspective. Moreover, it fails to fully conceptualise the social, relational, and contextual complexities of privacy and the vital role it has on academics' ability to form their identity. To address these knowledge gaps, this paper draws on the "social theory of privacy" to examine how academics socially negotiate privacy boundaries and the influence these negotiations have on their identity. Data were gathered through a qualitative case study analysis of a higher education institution in the United Kingdom (UK). The findings reveal how academic preferences and context-dependent social meanings influence the construction of dialectical privacy boundaries that allow academics to create and maintain various personal boundaries. These negotiated boundaries are influenced by the nature of the relationship between individuals, the levels of trust between colleagues, and the social norms governing workplace relationships. The findings also reveal how these negotiated privacy boundaries provide an intimate territory within which academics co-construct their identity through a complex series of social interactions occurring over time.

Biological invasion by exotic organisms became a key issue, a concern associated to the deep impacts on several domains described as resultant from such processes. A better understanding of the processes, the identification of more susceptible areas, and the definition of preventive or mitigation measures are identified as critical for the purpose of reducing associated impacts. The use of species distribution modeling might help on the purpose of identifying areas that are more susceptible to invasion. This paper aims to present preliminary results on assessing the susceptibility to invasion by the exotic species Acacia dealbata Mill. in the Ceira river basin. The results are based on the maximum entropy modeling approach, considered one of the correlative modelling techniques with better predictive performance. Models which validation is based on independent data sets present better performance, an evaluation based on the AUC of ROC accuracy measure.

Cured pork loins are sausages with a production tradition in several regions worldwide. They are made from one of the noblest cuts of pork, and for this reason cured loins are one of the most expensive pork meat products. Establishing the correct shelf life allows products to be accepted by the consumer, and to avoid the costs associated with shorter shelf lives. The aim of this study is: (1) to establish proper shelf life by evaluating the willingness of participants to consume and the sensory modifications that occur during prolonged storage via Check All That Apply (CATA) questions; and (2) to study the behavior of Listeria monocytogenes through a microbial challenge test. Sliced cured pork loins can be stored at 6 ± 1 °C for 105 days while maintaining a consumer acceptance of more than 75%. The freshness loss was associated mainly with a decrease in aromatic notes (particularly the smoke and cured aroma), and with the appearance of spoiled characteristics, specifically a sour/vinegar aroma and acidic taste that were detected by a reduced proportion of participants. The freshness evaluation was positively influenced by the typical characteristics of cured products, such as color and a garlic and wine aroma. Sour/vinegar aroma and acidic taste were the attributes most associated with higher freshness penalization. During the period of the test, Listeria monocytogenes inoculated onto the cured loin slices did not grow.

Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases.

We have investigated the complex karyotype of a living zebra-donkey hybrid for the first time using chromosome-specific painting probes produced from flow-sorted chromosomes from a zebra (Equus burchelli) and horse (Equus caballus). As the chromosomes proved difficult to distinguish from one another, a successful new strategy was devised to resolve the difficulty and characterize each chromosome. This was based on selecting five panels of whole chromosome painting probes that could differentiate zebra and donkey chromosomes by labelling the probes with either FITC or Cy3 fluorochromes. Each panel was hybridized sequentially to the same G-Q-banded metaphases and the results combined so that every zebra and donkey chromosome in each suitable metaphase could be identified. A diploid number of 2n = 53, XY was found, containing haploid sets of 22 chromosomes from the zebra and 31 chromosomes from the donkey, without evidence of chromosome rearrangement. This new strategy, developed for the first time, may have several applications in the resolution of other complex hybrid karyotypes and chromosomal aberrations.

For a long time, sample preparation was unrecognized as a critical issue in the analytical methodology, thus limiting the performance that could be achieved. However, the improvement of microextraction techniques, particularly microextraction by packed sorbent (MEPS) and solid-phase microextraction (SPME), completely modified this scenario by introducing unprecedented control over this process. Urine is a biological fluid that is very interesting for metabolomics studies, allowing human health and disease characterization in a minimally invasive form. In this manuscript, we will critically review the most relevant and promising works in this field, highlighting how the metabolomic profiling of urine can be an extremely valuable tool for the early diagnosis of highly prevalent diseases, such as cardiovascular, oncologic and neurodegenerative ones.

Purpose: Quality certification helps companies to improve efficiency and performance. The aim of this study is to analyze the differences between certified and non-certified hotels regarding the implementation of quality management practices, the performance and the competitive advantage, and the changes in organizational structure. Design/methodology/approach: The paper classifies the hotels in two groups: quality certified and non-certified hotels. It then examines the differences between both groups. Findings: The findings show that certified hotels develop quality management practices in a higher extent, achieve better performance levels and a differentiation competitive advantage, and have higher levels of formalization and interdepartmental coordination. Originality/value: The contribution of the paper is to analyze if quality certification adds value for the hotel industry.

Composites of recycled high density polyethylene (HDPE-R) and coffee dregs (COFD) were elaborated. The blends were made at the proportions of 100-0, 90-10, 80-20, 70-30, 60-40, 50-50 and 40-60% polymer-filler ratio. The materials were evaluated through scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TGA), and compressive resistance test. The compounding was done using a two-stage co-kneader system extruder, and then cylindrical specimens were injection molded. All composites had a fine dispersion of the COFD into the polymeric matrix. The composites degraded in two steps. The first one was in a temperature lower than the neat HDPE, but higher than the average processing temperature of the polymer. The melting temperature and the degree of crystallinity of the composites resulted similar to the neat HDPE ones. The compressive moduli of the composites resulted similar to the neat polymer one. The results show that these composites have interesting properties as a building material.

Left ventricular noncompaction is an unusual but increasingly recognized cardiomyopathy, the etiology of which is still not definitely established. Clinical presentation includes a wide spectrum of scenarios, including heart failure, thromboembolism and malignant arrhythmias, with half of deaths occurring suddenly. Early detection of LVNC is therefore essential to prevent sudden cardiac death. To our knowledge, this is the first report of the presence of cardiac sympathetic nervous dysfunction, assessed by 123iodine-metaiodobenzylguanidine myocardial scintigraphy, in a patient with LVNC, preserved left ventricular systolic function and exercise-induced nonsustained ventricular tachycardia. This finding may be related to the increased arrhythmic risk observed in this cardiomyopathy, giving a new insight into the pathophysiology of LVNC. Resumo: O miocárdio não-compactado (MNC) é uma miocardiopatia que, embora rara, tem sido gradualmente mais descrita. O espectro de apresentação clínica é variável, incluindo insuficiência cardíaca, fenómenos tromboembólicos e arritmias, sendo que metade das mortes ocorre subitamente (MSC). Por conseguinte, o diagnóstico precoce e correto do MNC é fundamental para a prevenção da MSC. O presente artigo ilustra pela primeira vez a presença de disfunção neuronal simpática, avaliada por cintigrafia cardíaca com 123I-metaiodobenzilguinadina, num doente com MNC, função sistólica ventricular esquerda preservada e taquicardia não sustentada induzida pelo esforço. A presença de alterações na actividade adrenérgica cardíaca pode estar relacionada com o maior risco arrítmico característico desta miocardiopatia, podendo contribuir para o melhor esclarecimento da sua patofisiologia. Keywords: Cardiac 123I-MIBG scintigraphy, Left ventricular noncompaction, Arrhythmias, Palavras-chave: Cintigrafia cardíaca com 123I-MIBG, Miocárdio não-compactado, Arritmias

The Serra de São José is a mountain range within Cerrado (Brazilian savanna) biome, situated in the south of Minas Gerais state, Brazil. The predominant vegetation of the study area is campo rupestre (Brazilian rocky savanna). The latter formation, better known from the Espinhaço Chain, is the scene of many speciation events and comprises several rare species. Thirteen species of the family Lentibulariaceae belonging to the two genera occurring in Brazil are listed, briefly diagnosed, and ecologically commented herein.

Background: Traditional Chinese medicine (TCM) may be understood as a system of sensations and findings designed to establish the functional vegetative state of the body. This state may be treated by several therapeutic methods such as acupuncture, Chinese pharmacotherapy, dietetics, Tuina, and Qigong. Nowadays, as a result of several evidence-based reported beneficial effects over specific pathological conditions, there is an increasing tendency to integrate some of these practices in Western medicine. The main goal of this study was to perform a bibliometric analysis of TCM scientific production between 1982 and 2016 indexed in PubMed, by analyzing several parameters including time and location distribution, publication quality, experimental design, and treatment methods. Methods: The methodology was based on the quantitative inventory of published scientific research indexed in PubMed medical subject headings (MeSH), sorted within the broad term “Traditional Chinese Medicine” and integrating the following criteria as limit filters: “Species: Humans”, “Article Type: Clinical Trial”. In addition, the articles’ triage was ruled by temporal limitations set between 1945 and 2016. Results: The overall analysis of data allowed observation of an average annual growth of approximately 33%, with a productive peak of 122 articles in 2007. The scientific production was distributed in 27 countries, led by China (76.1%), followed by the United States of America (3.0%) and South Korea (2.1%). A significant amount of references were published in Chinese journals: more than 50%; however, these journals had a low impact factor. The most cited treatments in the keywords section of the articles were phytotherapy (55%) and acupuncture (40%). Conclusion: The increasing demand for TCM seems to be due to factors such as lower side effects and greater efficacy in some patients not responding well to conventional therapy. As a result, a considerable amount of TCM science-based literature has been produced, supporting the rational integration of these practices in Western healthcare systems and research. Our results show that the quality of TCM research and inherent publications have been increasing over the last decades, with a higher incidence of studies published in well-ranked journals.

Background: Osteoarthritis is a widespread chronic disease seen as a continuum of clinical occurrences within several phases, which go from synovial inflammation and microscopic changes of bone and cartilage to painful destructive changes of all the joint structures. Being the most common joint disease, it is the leading cause of disability in working individuals above 50 years of age. In some cases, conventional treatments produce just a mild and brief pain reduction and have considerable side-effects. Contemporary Traditional Chinese Medicine (TCM) is a model of systems biology based on a logically accessible theoretical background. It integrates several therapeutic approaches, among them acupuncture, which has shown effective results in the treatment of knee and hip osteoarthritis, minimizing pain, improving functionality and consequently leading to a better quality of life. Methods: The present case study included two patients with clinical signs of osteoarthritis and diagnosis of medial pain, as defined by the Heidelberg Model of TCM. Over 6 weeks, those patients were treated with acupuncture, with a frequency of one session a week. The sessions lasted for thirty minutes and were based on the needling of 4 local acupoints. Before and after each session, pain and mobility assessments were performed. Results: The results were positive, with significant reduction of pain and increased knee joint flexion amplitude and mobility. Conclusion: Acupuncture was effective as an alternative or complementary treatment of knee osteoarthritis, with high levels of improvement within a modest intervention period.

Los hoteles necesitan cada vez más información para su correcta gestión y para maximizar su desempeño o éxito empresarial. De esta forma, en este estudio se analizan una serie de variables estratégicas clave que influyen directamente sobre el desempeño hotelero. Estas variables son el tamaño, el tipo de gestión y la categoría de los hoteles. En este trabajo, empleando la teoría de los grupos estratégicos, se han agrupado los hoteles españoles de entre 3 a 5 estrellas en función de cada una de estas variables estratégicas con el objetivo de determinar si influyen significativamente sobre el desempeño hotelero y en qué sentido. Entre los resultados que se han obtenido destacan el hecho de que a mayor tamaño y categoría, mayor es el desempeño que alcanzan los hoteles. Así mismo, los hoteles que pertenecen a cadenas alcanzan niveles de desempeño mayores que los independientes. Por lo tanto, de esta investigación se deducen importantes implicaciones para la dirección hotelera.

We report the isolation of Fonsecaea pedrosoi from thorns of the plant Mimosa pudica L. at the place of infection identified by one of our patients. Clinical diagnosis of chromoblastomycosis was established by direct microscopic examination and cultures from the patient's lesion. The same species was isolated from the patient and from the plant. Scanning electron microscopy of the surface of the thorns showed the characteristic conidial arrangement of F. pedrosoi. These data indicate that M. pudica could be a natural source of infection for the fungus F. pedrosoi.

Holt-Oram syndrome is clinically characterized by morphological abnormalities of the upper limbs and congenital cardiac defects. Although the disease is congenital, the diagnosis may only be made later in life. It is a rare autosomal dominant disorder, caused by a mutation in the TBX5 gene located on chromosome 12, but sporadic cases have also been reported. We describe the case of a 75-year-old man with known morphological alterations of the upper limbs since birth and congenital cardiac defect (atrial septal defect), who later in life also manifested with advanced atrioventricular block. Resumo: A síndrome de Holt-Oram é caracterizada pela associação de defeitos morfológicos dos membros superiores com defeitos cardíacos congénitos. Apesar de ser uma doença congénita, o seu diagnóstico pode só ser feito numa idade mais avançada. É uma doença autossómica dominante rara, devido à mutação do gene T-BX5, localizado no cromossoma 12, mas casos esporádicos também já foram reportados. Descrevemos o caso de um doente de 75 anos, com alterações morfológicas dos membros superiores, presentes desde o nascimento e defeito cardíaco (comunicação inter-auricular) diagnosticado na adolescência, que numa idade mais avançada apresentou bloqueio aurículo-ventricular completo. Keywords: Holt-Oram syndrome, Hand-heart syndrome, T-box, Atrial septal defect, Palavras-chave: Síndrome Holt-Oram, Síndrome mão-coração, T-BOX, Defeito septo interauricular

The objective of this work was to determine the methemoglobinemia and correlate with dapsone levels in multibacillary leprosy patients under leprosy multi-drug therapy. Thirty patients with laboratory and clinical diagnosis of multibacillary leprosy were enrolled. Dapsone was analyzed by high performance liquid chromatography and methemoglobinemia by spectrophotometry. The mean dapsone concentrations in male was 1.42 g/mL and in female was 2.42 g/mL. The mean methemoglobin levels in male was 3.09 μg/mL; 191%, and in female was 2.84 ± 1.67%. No correlations were seen between dapsone levels and methemoglobin in male and female patients. Our results demonstrated that the dosage of dapsone in leprosy treatment does not promote a significant methemoglobinemia. Keywords: methahemoglobinemia, dapsone, leprosy

Se analizan retrospectivamente los resultados de 48 puentes distales al cuello del pie realizados en 43 pacientes, 32 hombres y 11 mujeres, con una edad media de 70 años, en un período de 20 meses. Se destaca la presencia de hipertensión (95%), coronariopatía (95%) y diabetes (93%).

The formation of reactive oxygen species (ROS) within cells causes damage to biomolecules, including membrane lipids, DNA, proteins and sugars. An important type of oxidative damage is DNA base hydroxylation which leads to the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 5-hydroxymethyluracil (5-HMUra). Measurement of these biomarkers in urine is challenging, due to the low levels of the analytes and the matrix complexity. In order to simultaneously quantify 8-oxodG and 5-HMUra in human urine, a new, reliable and powerful strategy was optimised and validated. It is based on a semi-automatic microextraction by packed sorbent (MEPS) technique, using a new digitally controlled syringe (eVol(®)), to enhance the extraction efficiency of the target metabolites, followed by a fast and sensitive ultrahigh pressure liquid chromatography (UHPLC). The optimal methodological conditions involve loading of 250 µL urine sample (1:10 dilution) through a C8 sorbent in a MEPS syringe placed in the semi-automatic eVol(®) syringe followed by elution using 90 µL of 20% methanol in 0.01% formic acid solution. The obtained extract is directly analysed in the UHPLC system using a binary mobile phase composed of aqueous 0.1% formic acid and methanol in the isocratic elution mode (3.5 min total analysis time). The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), extraction yield, accuracy, precision and matrix effect. Satisfactory results were obtained in terms of linearity (r(2) > 0.991) within the established concentration range. The LOD varied from 0.00005 to 0.04 µg mL(-1) and the LOQ from 0.00023 to 0.13 µg mL(-1). The extraction yields were between 80.1 and 82.2 %, while inter-day precision (n = 3 days) varied between 4.9 and 7.7 % and intra-day precision between 1.0 and 8.3 %. This approach presents as main advantages the ability to easily collect and store urine samples for further processing and the high sensitivity, reproducibility, and robustness of eVol(®)MEPS combined with UHPLC analysis, thus retrieving a fast and reliable assessment of oxidatively damaged DNA.