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Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n = 12). Expression values for individual miRs were normalized to miR-16-5p, which was the least variant among the control skin and BCC samples. We found that (i) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared with control skin, (ii) miR-181c-5p is downregulated in superficial compared with invasive (nodular/infiltrative) BCC, and (iii) miR-22-5p and miR-708-5p are upregulated in infiltrative compared with superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared with nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under the curve, 0.94–0.98), whereas the capacity to discriminate between superficial and invasive subtypes was less robust (area under the curve, 0.7–0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.

Introduction: The major vascular cause of dementia is cerebral small vessel disease (SVD). The diagnosis of SVD relies on MRI findings, including white matter hyperintensities (WMH) amongst others. Chronic hypertension and neuroinflammation are recognized as important risk factors for SVD and for the conversion of normal-appearing white matter (NAWM) into WMH. Unfortunately, most studies investigating the role of neuroinflammation in WMH relied on peripheral blood markers as a proxy for inflammation in the brain itself. Whether such markers accurately capture inflammatory changes within the cerebral white matter remains unknown. Therefore, we aimed to comprehensively investigate the impact of hypertension on perivascular- and neuroinflammation in both WMH and NAWM. Methods: We conducted high-field (7 Tesla) MRI on human post-mortem brains (n=22) of elderly people with chronic hypertension (n = 17) and age-matched controls (n=5) to assess SVD burden, focusing on the analysis of WMH by Fazekas score severity and volumetry. After careful evaluation, brain axial biopsies were taken, from which paraffin sections were cut and (immuno-histochemistry (IHC)) performed to examine neuroinflammation mediated by both microglia and astroglia, and perivascular inflammation. To accurately co-register our MRI findings to IHC data, we developed a custom written MATLAB script to compare changes in WMH on MRI to microscopical changes in IHC. Results: WMH were characterized by more activated microglia and astrogliosis compared to surrounding NAWM. Notably, hypertension was associated with a larger (perivascular) inflammatory response in both WMH and NAWM, suggesting that neuroinflammation plays a crucial role in the pathogenesis of WMH in individuals with hypertension. Discussion: Our results indicate that neuro(vascular)inflammation at the level of the brain itself is involved in the etiology of WMH. Future therapeutic strategies focusing on multitarget interventions including antihypertensive treatment as well as treatment against neuroinflammation may ameliorate WMH progression.

Objective: The objective of this quality improvement project was to evaluate the effectiveness of a succinct health literacy training for providers at a demanding federally qualified health center. Methods: One group, pretest-posttest design was used to measure for a change in knowledge regarding the effects of limited health literacy, a change in self-reported measure of routine screening for limited health literacy and a change in self-reported utilization of patient-centered communication techniques. Results: The average percentage of correct responses on the Health Literacy Knowledge Check showed significant improvement from 23.6% (SD = 18.1%) to 63.9% (SD = 25.3%), p < .001. There were no significant changes in median responses at pre- and post-intervention for self-reported use of screening and communication techniques (all p > .05). Conclusion: This brief training was effective at improving participants' knowledge of health literacy but did not improve use of recommended communication techniques or screening for health literacy. The results suggest that emphasizing a universal precautions approach to health literacy may be more effective with participants who work in high-volume clinics. Practice implications: For high-volume clinics, a brief training may improve participants' knowledge but does not increase use of actual communication techniques based on self-report.

Background: The accurate segmentation, labeling and quantification of cerebral blood vessels on MR imaging is important for basic and clinical research, yet results are not generalizable, and often require user intervention. New methods are needed to automate this process. Purpose: To automatically segment, label and quantify Circle of Willis (CW) arteries on Magnetic Resonance Angiography images using deep convolutional neural networks. Materials and methods: MRA images were pooled from three public and private databases. A total of 116 subjects (mean age 56 years ± 21 [standard deviation]; 72 women) were used to make up the training set (N=101) and the testing set (N=15). In each image, fourteen arterial segments making up or surrounding the CW were manually annotated and validated by a clinical expert. Convolutional neural network (CNN) models were trained on a training set to be finally combined in an ensemble to develop eICAB. Model performances were evaluated using (1) quantitative analysis (dice score on test set) and (2) qualitative analysis (external datasets, N=121). The reliability was assessed using multiple MRAs of healthy participants (ICC of vessel diameters and volumes on test-retest). Results: Qualitative analysis showed that eICAB correctly predicted the large, medium and small arteries in 99±0.4%, 97±1% and 88±7% of all images, respectively. For quantitative assessment, the average dice score coefficients for the large (ICAs, BA), medium (ACAs, MCAs, PCAs-P2), and small (AComm, PComm, PCAs-P1) vessels were 0.76±0.07, 0.76±0.08 and 0.41±0.27, respectively. These results were similar and, in some cases, statistically better (p

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P

Introduction: Carbapenemase-producing Enterobacteriaceae (CPE) are of global concern due to the growing number of patients who acquire them and their association with high mortality rates. Although there are some reports of endemicity in developing countries, little is known about this microorganism, and Ecuador is not an exception. Subsequently, our objective was to clinically and molecularly characterize carbapenemase producing-Enterobacteriaceae in intensive care units (ICUs) in Guayaquil, Ecuador. Methods: To determine CPE colonization, we obtained perineal and inguinal swabs from patients admitted to seven intensive-care adult units in Guayaquil-Ecuador between February and April 2016. The Centers for Disease Control and Prevention (CDC) laboratory protocol and chromogenic agar were used to process the cultures. Polymerase chain reaction was used to confirm carbapenemase production. Genotypic analysis was performed by Multilocus Sequence Typing (MLST) and pulsed-field electrophoresis (PFEG). Demographic and clinical data were obtained from the electronic charts and patient’s relatives. Results: Six hundred seventy-seven patients were included in the study, of whom 255 were colonized/infected by CPE. The CPE prevalence was 37.67%. Previous use of antimicrobials, use of invasive procedures and being burned at admission were associated with CPE. The most frequent infection was found after a surgical procedure. Klebsiella pneumoniae (n = 249) was the predominant microorganism harbouring blaKPC, followed by Enterobactercloacae (n = 8), Klebsiella aerogenes (n = 4), Escherichia coli (n = 4) and Klebsiella oxytoca (n = 1). NDM was present in Proteus mirabilis. The strains were distributed in 19 sequence types (ST), and 10 were not reported previously in Ecuador. ST 258 was the sequence type isolated most frequently. Conclusion: This study shows a high prevalence of CPE in ICUs, particularly K. pneumoniae blaKPC ST 258. The identification of KPC alleles may help to understand the routes of dissemination and control spread within ICUs in Guayaquil, Ecuador. Keywords: Carbapenemase, Intensive care units, Prevalence

Background: The amyloid cascade hypothesis characterizes the stereotyped progression of pathological changes in Alzheimer's disease (AD) beginning with beta amyloid deposition, but does not address the reasons for amyloid deposition. Brain areas with relatively higher neuronal activity, metabolic demand, and production of reactive oxygen species in earlier life may have higher beta amyloid deposition in later life. The aim of this study was to investigate early life patterns of perfusion and late life patterns of amyloid deposition to determine the extent to which normative cerebral perfusion predisposes specific regions to future beta amyloid deposition. Materials and Methods: One hundred twenty-eight healthy, older human subjects (age: 56–87 years old; 44% women) underwent positron emission tomography (PET) imaging with [11C]PiB for measures of amyloid burden. Cerebral perfusion maps derived from 47 healthy younger adults (age: 22–49; 47%) who had undergone single photon emission computed tomography (SPECT) imaging, were averaged to create a normative template, representative of young, healthy adults. Perfusion and amyloid measures were investigated in 31 cortical regions from the Hammers atlas. We examined the spatial relationship between normative perfusion patterns and amyloid pathophysiology. Results: The pattern of increasing perfusion (temporal lobe

The clinical, microbiological, and histopathological findings of six patients with mucosal leishmaniasis are reported. Five of these patients were Spanish with no history of travel abroad, while the other was from Bolivia but had lived in Spain for more than 5 years. Two patients had no underlying disease, while the other four had several other medical conditions. Lesions were located in the nose in three patients and in the larynx in the other three. Symptoms included difficulty in swallowing, nasal obstruction, dysphonia, and polypoid lesions mimicking cancer. The diagnosis was based on the identification of parasites, or on PCR assay or culture. Five patients were treated with liposomal amphotericin B and the other with antimonial compounds.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. Study design: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120). Results: In 69 patients (42 males, 27 females, mean age 44.6 ± 13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤ 60 ml/min/1.73 m2 (log Rank 12.423, p = 0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p = 0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. Resumen: El objetivo de este estudio es realizar un mapa del tratamiento actual de la enfermedad de Fabry en España, analizando el efecto de diferentes factores en el desarrollo de eventos clínicos a largo plazo. Diseño del estudio: Análisis observacional retrospectivo multicéntrico. Criterios de inclusión: pacientes diagnosticados y tratados de enfermedad de Fabry. Se recogieron datos generales en relación con el diagnóstico, síntomas y tipo mutación, tipo de tratamiento recibido, evolución renal y cardiológica. Durante un tiempo de seguimiento de 60 meses (24-120), se recogió el primer evento clínico tras el inicio de tratamiento sustitutivo enzimático definido como mortalidad, evento renal, cardiológico o neurológico. Resultados: Se incluyeron 69 pacientes (42 H, 27 M) con una edad media de 44,6 ± 13,7 años. A los cinco años de tratamiento, el FGe y la hipertrofia ventricular izquierda se mantuvieron estables, y la albuminuria tiende a disminuir, siendo este descenso más significativo en el grupo de pacientes tratados con beta-galactosidasa (de 242 a 128 mg/g (p = 0,05). Veintiún pacientes sufrieron un evento clínico (30%): seis renales, dos neurológicos y 13 cardiológicos (incluidas tres muertes). Los pacientes con ERC (FGe

Thallium (Tl) and its compounds are toxic to biota even at low concentrations but little is known about Tl concentration and speciation in soils. An understanding of the source, mobility, and dispersion of Tl is necessary to evaluate the environmental impact of Tl pollution cases. In this paper, we examine the Tl source and dispersion in two areas affected by abandoned mine facilities whose residues remain dumped on-site affecting to soils and sediments of natural water courses near Madrid city (Spain). Total Tl contents and partitioning in soil solid phases as determined by means of a sequential extraction procedure were also examined in soils along the riverbeds of an ephemeral and a permanent streams collecting water runoff and drainage from the mines wastes. Lastly, electronic microscopy and cathodoluminescence probe are used as a suitable technique for Tl elemental detection on thallium-bearing phases. Tl was found mainly bound to quartz and alumino-phyllosilicates in both rocks and examined soils. Besides, Tl was also frequently found associated to organic particles and diatom frustules in all samples from both mine scenarios. These biogenic silicates may regulate the transfer of Tl into the soil-water system., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The Circular Mausoleum tomb in the Roman Necropolis of Carmona was carved on a calcarenite sequence in an ancient quarry located in the town of Carmona, Southern Spain. This rock-cut tomb, representative of Roman burial practices, currently suffers from serious deterioration. A detailed survey over several years permitted the identification of the main tomb's pathologies and damaging processes, which include loss of material (scaling, flaking, granular disintegration), surface modifications (efflorescences, crusts and deposits) and extensive biological colonization. The results obtained in this study indicated that anthropogenic changes were largely responsible and enhanced the main alteration mechanisms observed in the Circular Mausoleum. Based on the deterioration diagnosis, effective corrective actions were proposed. This study shows that any conservative intervention in the interior of the tomb should be preceded by accurate in situ measurements and laboratory analyses to ascribe the source of the deterioration damages and thus designing effective treatments., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The formation of scorodite is an important mechanism for the natural attenuation of arsenic in a wide range of environments. It is dumped on site by metallurgical industries to minimize arsenic release. However, the long-term stability of these deposits is unclear. Sequential As extractions and synchrotron-based X-ray absorption near-edge structure (XANES) spectroscopy were used to determine both As and Fe speciation in a small catchment area affected by a scorodite-rich waste pile at an abandoned smelting factory. Our results indicate that this deposit behaves as an acute point source of As and metal pollution and confirms the strong association of As(V) with Fe(III) oxide phases, highlighting the important role of ferrihydrite as an As scavenger in natural systems. In this seasonally variable system, other trapping forms such as jarosite-like minerals also play a role in the attenuation of As. Overall, our results demonstrate that scorodite should not be considered an environmental stable repository for As attenuation when dumped outside because natural rainfall and the resulting runoff drive As dispersion in the environment and indicate the need to monitor and reclamate As-rich mine deposits., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The luminescence (cathodoluminescence and thermoluminescence) properties of natural bones (Siberian mammoth and adult elephant), commercial hydroxyapatite and collagen were analyzed. Chemical analyses of the natural bones were determined using by Electron Probe Micro-Analysis (EMPA). Structural, molecular and thermal characteristics were determined by X-ray Diffraction (XRD), Raman spectroscopy and Differential Thermal and Thermogravimetric analysis (DTA-TG). Cathodoluminescence (CL) spectra of natural bones and collagen showed similar intense broad bands at 440 and 490 nm related to luminescence of the tetrahedral anion [Formula: see text] or structural defects. A weaker luminescence exhibited at 310 nm could be attributed to small amount of rare earth elements (REEs). Four luminescent bands at 378, 424, 468 and 576 nm were observed in the commercial hydroxyapatite (HAP). Both natural bones and collagen samples exhibited natural thermoluminescence (NTL) with well-defined glow curves whereas that the induced thermoluminescence (ITL) only appears in the samples of commercial hydroxyapatite and collagen. Additional explanations for the TL anomalous fading of apatite, as a crucial difficulty performing dosimetry and dating, are also considered., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In the last decades, damages on building materials and mural paintings were observed in Roman catacombs. The damages were due to extensive formation of biofilms induced by artificial illumination and humidity. Microenvironmental data (temperature, CO(2) concentration, humidity, and atmospheric pressure) clearly showed the negative influence of visitors. Increasing heat, light and water vapour condensation into corridors and cubicles favoured biofilm development. The composition of biofilms was different and depended mainly on distance to illumination sources and humidity, thus denoting the influence of light on the growth of phototrophic microorganisms in the catacombs. In addition, biofilm distribution was governed by the type of material to be colonised. This study shows that countermeasures are needed to prevent deterioration of hypogean environments.

This study presents a methodology to estimate traffic emissions inventories for the case of city centres. It deals with the problem in a structured manner, identifying the sources and the formats of the input data as well as labelling the steps needed to perform the calculation. It describes a method to calculate the total mileage driven around the city using the concept of mileage per zone. Although the methodology employs a classical approach through the use of emission factors developed for mean speeds, it also discusses the possibility of applying these factors to instantaneous speeds. Finally, the study focuses on the influence of two critical factors: time resolution and the estimate of the total mileage. In both cases, the results indicate that the assumptions made are adequate and yield accurate results. The methodology has been applied to the city of Madrid as an example.

A pathogenesis model based on the interaction between Caenorhabditis elegans and bacterial opportunistic pathogens has recently been developed. In the case of Pseudomonas aeruginosa, the model is based on three different modes of nematode killing (fast killing, slow killing and lethal paralysis) by virulent bacteria that has been incubated in different nutrient media. Using parametric statistics and Probit analysis, we test the reliability of the three different killing systems with respect to bacterial virulence. To accomplish this, we use three P. aeruginosa strains, each with a different level of virulence and one strain of non-virulent Escherichia coli. Probit function proved to be effective in quantifying the virulence of P. aeruginosa. The results of the killing curve analysis using the Probit function demonstrates that the slow-killing test is the most reliable method for quantifying virulence using the C. elegans model of bacterial pathogenesis. Although the greatest virulence differences are observed after long periods of incubation, the Probit analysis clearly shows that the death kinetics of C. elegans depend on the first hours of nematode/bacteria interaction. In contrast, fast killing seems to be non-specific, at least under our experimental conditions, since the killing rates of virulent P. aeruginosa and non-virulent E. coli strains were indistinguishable.