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There has been significant increase in the use of molecular tools for the diagnosis of invasive aspergillosis (IA) and mucormycosis. However, their range of detection may be too limited as species diversity and coinfections are increasing. Here, we aimed to evaluate a molecular workflow based on a new multiplex PCR assay detecting the whole Aspergillus genus and the Mucorales order followed by a species-specific PCR or a DNA-sequencing approach for IA and/or mucormycosis diagnosis and species identification on serum. Performances of the MycoGENIE Aspergillus spp./Mucorales spp. duplex PCR kit were analyzed on a broad range of fungal strains and on sera from high-risk patients prospectively over a 12-month period. The kit allowed the detection of nine Aspergillus species and 10 Mucorales (eight genera) strains assessed. No cross-reactions between the two targets were observed. Sera from 744 patients were prospectively analyzed, including 35 IA, 16 mucormycosis, and four coinfections. Sensitivity varies from 85.7% (18/21) in probable/proven IA to 28.6% (4/14) in COVID-19-associated pulmonary aspergillosis. PCR-positive samples corresponded to 21 A. fumigatus, one A. flavus, and one A. nidulans infections. All the disseminated mucormycosis were positive in serum (14/14), including the four Aspergillus coinfections, but sensitivity fell to 33.3% (2/6) in localized forms. DNA sequencing allowed Mucorales identification in serum in 15 patients. Remarkably, the most frequent species identified was Rhizomucor pusillus (eight cases), whereas it is barely found in fungal culture. This molecular workflow is a promising approach to improve IA and mucormycosis diagnosis and epidemiology.

The Chicago Classification is the most used classification for primary esophageal motility disorders (PEMD). This classification was recently updated to the 4.0 version. This opinion piece focuses on the possible implications for the treatment of PMED determined by the new classification. Chicago Classification 4.0 included two new concepts for the diagnosis of achalasia: (1) type III achalasia diagnosis demands 100% absent peristalsis defined as either failed peristalsis or spasm; (2) “inconclusive diagnosis of achalasia” was added as a possibility. Both may decrease unnecessary treatment. Esophagogastric junction outflow obstruction, distal esophageal spasm, and hypercontractile esophagus were only considered clinically significant when correlated to supportive testing and relevant clinical symptoms and in the absence of gastroesophageal reflux disease. This may decrease the surge of treatment, especially peroral endoscopic myotomy, based solely on manometric diagnosis.

Resumen Objetivos Conocer la prevalencia de enfermedad renal cronica (ERC) y determinar los factores asociados al deterioro de la funcion renal en poblacion asistida en atencion primaria. Pacientes y metodo Estudio transversal y multicentrico realizado en los pacientes basales del estudio IBERICAN (identificacion de la poblacion espanola de riesgo cardiovascular y renal). Se considero ERC a un filtrado glomerular estimado (FGe) Resultados Se incluyeron 7.895 pacientes (edad media 57,9 ± 14,8 anos; 54,5% mujeres). El 14,4% (IC 95%: 13,6-15,1) presentaba ERC; en hombres un 16,1% (IC 95%: 14,9-17,3) y en mujeres un 12,9% (IC 95%: 11,9-14,0). Se observo un aumento continuo de la prevalencia con la edad (24,8% ≥ 65 anos) y con la agregacion de FRCV. Las variables que mas se asociaron a la probabilidad de padecer ERC fueron hipertrofia ventricular izquierda (OR: 1,95; p Conclusiones Catorce de cada 100 pacientes incluidos en el estudio IBERICAN presenta ERC. La prevalencia de ERC afecta a la cuarta parte de pacientes ≥ 65 anos y aumenta exponencialmente con la agregacion de FRCV.

An increased transdiaphragmatic pressure gradient (TGP) is a main element for distal gastroesophageal reflux disease (GERD). The role of TGP for proximal reflux is still unclear. This study aims to evaluate the presence, severity, and importance of proximal reflux in relationship to the TGP, comparing healthy volunteers, obese individuals, and patients with chronic obstructive pulmonary disease (COPD). We studied 114 individuals comprising 19 healthy lean volunteers, 47 obese individuals (mean body mass index 45 ± 7 kg/m2), and 48 patients with COPD. All patients underwent high-resolution manometry and dual-channel esophageal pH monitoring. Esophageal motility, thoracic pressure (TP), abdominal pressure (AP), TGP, DeMeester score, and % of proximal acid exposure time (pAET) were recorded. Pathologic distal GERD was found in 0, 44, and 57% of the volunteers, obese, and COPD groups, respectively. pAET was similar among groups, only higher for obese individuals GERD + as compared to obese individuals GERD − and COPD GERD −. pAET did not correlate with any parameter in healthy individuals, but it correlated with AP in the obese, TP in the COPD individuals, and TGP and DeMeester score in both groups. When all individuals were analyzed as a total, pAET correlated with AP, TGP, and DeMeester score. DeMeester score was the only independent variable that correlated with pAET. Our results show that (a) TGP is an important mechanism associated with distal esophageal acid exposure and this fact is linked with proximal acid exposure and (b) obesity and COPD both seem to be primary causes for GERD but not directly for proximal reflux.

The distribution and roles of the cannabinoid CB

Acute back pain (LA) is a considerable problem in any care setting. The Emergency Department (ED) intended to provide immediate, timely and effective care. Our objective was to estimate the prevalence and describe the usual care process.To estimate prevalence, a random sample was included of 5,333 consultations admitted in ED at hospital XX between January and December 2016. LA cases were defined according to the diagnosis at arrival. A retrospective cohort with all LA cases was used to describe complementary studies and therapeutic behaviors established in ED or within the subsequent 30 days outpatient follow-up.LA represented 4.37% (95% CI: 3.83-4.95%) of consultations. A total of 1,096 cases of LA were included: mean age of 53.26 ± 19.85 years, 55.93% (613) female sex and few comorbidities. The median attention time was 3.28 hours and 6.20% was admitted. 70% (778) received treatment in CEA, being the most used administration routes: intravenous (61.86%), and intramuscular (20.62%). The analgesics used were: 55.38% corticosteroids, 55.02% NSAIDs, 34.85% opioids. The complementary studies requested during ED or until 30 days after discharge, were: 52.19% laboratory, 47.17% radiography, 28.38% RM, 10.77% tomography, 9.12% interventionism.This study provides epidemiological data of LA in Argentina and demonstrates the need to promote the rational use of resources.La lumbalgia aguda (LA) es un problema en diferentes ámbitos de atención. La Central de Emergencias de Adultos (CEA) intenta brindar atención inmediata, especializada y eficaz. Nuestro objetivo fue estimar la prevalencia y describir el proceso de atención habitual.Para la estimación de prevalencia, se incluyó una muestra aleatoria de 5,333 consultas admitidas en CEA de un solo hospital entre Enero y Diciembre de 2016. Se definió como numerador a los casos de LA según diagnóstico de triaje al ingreso. Una cohorte retrospectiva con todos los casos de LA se utilizó para describir estudios complementarios y conductas terapéuticas instaurados en CEA, con seguimiento ambulatorio posterior.La lumbalgia aguda representó 4.37% (IC 95%: 3.83-4.95%) de las consultas. Se incluyeron 1,096 casos de LA: edad media de 53.26 ± 19.85 años, 55.93% (613) sexo femenino y escasas comorbilidades. La mediana de tiempo de atención fue de 3.28 horas y se internó 6.20%, 70% (778) recibió tratamiento en CEA, las vías de administración más utilizadas fueron: endovenosa (61.86%) e intramuscular (20.62%). Los analgésicos utilizados fueron: 55.38% corticoides, 55.02% AINE, 34.85% opiáceos. Los estudios complementarios solicitados en CEA o hasta los 30 días postegreso fueron: 52.19% laboratorio, 47.17% radiografía/s, 28.38% resonancia/s, 10.77% tomografía/s, 9.12% intervencionismo/s.Este estudio aporta datos epidemiológicos sobre LA y evidencia la necesidad de fomentar el uso racional de los recursos.

Background: The complex pathophysiology of Alzheimer’s disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. Methods: In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse model. Results: We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3–CA1 synapse, both basal synaptic transmission and long-term potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron–glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH animals. Conclusion: In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer’s disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the disease., Ministerio de Ciencia e Innovacion (SAF 2016-75959-R and PID2019-108992RB-I00) and NIH grant DA033760. I.B-C. is a recipient of a postdoctoral fellowship from Comunidad Autonoma de Madrid (PEJD-2017-POST/BMD-4478).

The determination of an asset&rsquo, s economic value has always been an important step in improving its management. The Madrid Region legislated the application of the first version of the Norma Granada as a method of appraising ornamental trees. However, the trees in the city of Madrid are only assessed in terms of ecosystem services (i-Tree Eco). A photograph of the asset to be appraised is often used in studies on the valuation of publicly-owned socio-environmental assets such as trees or landscapes. As a tree&rsquo, s value is very closely linked to its size and to a number of features that can be seen through direct observation of the specimen, it is important to verify the validity of photographs as a method for obtaining the public&rsquo, s opinion. This work presents a comparison between the valuations chosen by members of the public when observing the tree in situ and in a photograph. The aim is to verify the validity of photographs for their application to a larger sample and to understand qualitatively how citizens assess the trees in a city. The following appraisal methods were used: the American method, Council of Tree Landscape Appraisers (CTLA), Norma Granada and the Burnley method. The survey consisted of ten specimens from ten different species, and ten surveys were taken for each stem, making a total of 100 for each tree species and 1000 surveys in all. The surveys were done randomly and individually. Each interviewed chose one of the three values they were shown when observing the specimen in the photograph and in situ, 84% of the 1000 surveys gave as a result the same value choice when looking at the specimen on site and seeing it in a photograph.

Resumen Objetivo Describir la evolucion de 2 indicadores (de proceso y de calidad) relacionados con la toma de hemocultivos (HC) en la Central de Emergencias de Adultos del Hospital Italiano de Buenos Aires y describir la variacion de los mismos tras la implementacion de una intervencion educativa en mayo de 2016 para el personal de la salud acerca de la indicacion apropiada de HC y la tecnica adecuada para su extraccion. Materiales y metodos Se diseno una cohorte retrospectiva que incluyo la totalidad de consultas a la Central de Emergencias de Adultos durante 2015-2016. Se considero indicador de proceso la tasa de solicitud de HC, e indicadores de calidad, el porcentaje de HC contaminados y la tasa de verdaderos positivos. Ambos se midieron de manera mensual y prospectiva durante el periodo del estudio. Resultados La tasa ajustada anual de solicitud de HC fue del 4,9% (IC 95% 4,8-5) en 2015 y del 2,9% (IC 95% 2,8-2,9) en 2016. La tasa de HC contaminados fue del 4,5% en 2015 y del 4,3% postintervencion, mientras que los verdaderos positivos fueron un 8,3% en 2015 y un 12% postintervencion. Conclusiones Estos hallazgos demuestran la efectividad de la intervencion y la importancia de realizarlas periodicamente.

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract in the Western world. GERD pathophysiology is multifactorial. Different mechanisms may contribute to GERD including an increase in the transdiaphragmatic pressure gradient (TPG). The pathophysiology of GERD linked to TPG is not entirely understood. This review shows that TPG is an important contributor to GERD even when an intact esophagogastric barrier is present in the setting of obesity and pulmonary diseases. RESUMO A doença do refluxo gastroesofágico (DRGE) é a enfermidade mais comum do trato digestivo alto no mundo ocidental. A fisiopatologia da DRGE é multifatorial. Diferentes mecanismos podem contribuir para um aumento do gradiente pressórico transdiafragmático (GPT). A fisiopatologia da DRGE associada ao GPT não é totalmente compreendida. Esta revisão enfoca que o GPT é um importante contribuinte para DRGE mesmo na presença de uma barreira gastroesofágica intacta como na obesidade e doenças pulmonares crônicas.

Base excision repair (BER) is a major defense pathway against spontaneous DNA damage. This multistep process is initiated by DNA glycosylases that recognise and excise the damaged base, and proceeds by the concerted action of additional proteins that perform incision of the abasic site, gap filling and ligation. BER has been extensively studied in bacteria, yeasts and animals. Although knowledge of this pathway in land plants is increasing, there are no reports detecting BER in algae. We describe here an experimental in vitro system allowing the specific analysis of BER in the model alga Chlamydomonas reinhardtii. We show that C. reinhardtii cell-free extracts contain the enzymatic machinery required to perform BER of ubiquitous DNA lesions, such as uracil and abasic sites. Our results also reveal that repair can occur by both single-nucleotide insertion and long-patch DNA synthesis. The experimental system described here should prove useful in the biochemical and genetic dissection of BER in algae, and may contribute to provide a broader picture of the evolution and biological relevance of DNA repair pathways in photosynthetic eukaryotes.

Gastroesophageal reflux disease (GERD) is associated with different pulmonary diseases, including chronic obstructive pulmonary disease (COPD). Whether GERD is contributory to COPD severity remains unclear. This study aims to evaluate the contribution of GERD to the clinical manifestation of COPD based on ventilatory parameters and yearly clinical exacerbations. We studied 48 patients (56% females, age 66 years) with COPD. All patients underwent high-resolution manometry and esophageal pH monitoring. The patients were separated into two groups according to the presence of GERD. GERD was present in 21 (44%) patients. GERD + and GERD – groups did not differ in regard to gender, age, and body mass index. Pulmonary parameters were not different in the absence or presence of GERD. The number of yearly exacerbations was higher in patients GERD1. The severity of GERD (as measured by DeMeester score) correlated with the number of exacerbations. Our results show the following: 1) GERD does not influence pulmonary parameters and 2) GERD is associated with a higher number of annual clinical exacerbations. We believe GERD must be objectively tested in patients with COPD because the prevalence of GERD in these patients is underestimated when only symptoms are considered. GERD treatment might decrease the frequency of episodes of exacerbation.

Wear (pin-on-disk) tests of low-alloy powder steels (with 0.5 and 0.65% C) are performed after vacuum sintering combined with hardening. The studied alloying systems are 0.65% C + 1.5% Cr + 0.2% Mo, 0.65% C + 0.9% Ni + 0.9% Mo + 0.2% Mn and 0.5% C + 4% Ni + 1.5% Cu + 0.5% Mo. The wear resistance of the steels after the hardening sintering is an order of magnitude higher than after the conventional sintering. The wear resistance of the steels increases in the following order: pearlitic, pearlitic-bainitic, and martensitic structures. Accordingly, the hardness grows from 98 to 105 HRB.

Pathophysiology of gastroesophageal reflux disease (GERD) is multifactorial. An increased transdiaphragmatic pressure gradient (TPG) may be a main element for GERD in the obese patient. This study aims to evaluate the role of TPG in the physiopathology of GERD in obese individuals. We studied 47 unselected consecutive candidates for bariatric operations (body mass index (BMI) > 35). All patients underwent high-resolution manometry and esophageal pH monitoring. Individuals were grouped as GERD + or GERD − based on DeMeester score. Abdominal pressure (AP) and thoracic pressure (TP), transdiaphragmatic pressure gradient (AP-TP), and lower esophageal sphincter (LES) retention pressure (LES basal pressure-TPG) were determined. Manometric variables were compared with a group of 20 lean healthy individuals (BMI

The probability of an arc flash accident in electrical equipment or installations, such as power transformers, is present in all cases where electricity is present. In high voltage systems, the high level of supply required could lead to the release of energy levels high enough to cause serious injury to people around this equipment. For this reason, performing an arc flash analysis improves the safety conditions of workers, since, although in some cases injuries cannot be completely avoided, the severity of the injuries can be greatly reduced, and may even prevent deaths in the workplace. To this end, there are standards and computer tools to help calculate the energy released in the event of such accidents and to adopt appropriate corrective and preventive actions, in order to reduce the extent of possible injuries in the event of an accident. This work reviews the equations and analytical methodology for arc flash analysis, according to the most updated standards, and shows an applied study case of a power transformer located in an electric substation, indicating the most appropriate corrective and preventive actions to reduce the damage of this type of accidents in the transformer control cabinet.

Cardiovascular disease (CVD) is the major cause of premature death and disability experienced by Indigenous Australians and a key contributor to the life expectancy “gap” between Indigenous and non-Indigenous Australians. Because CVD strikes Indigenous Australians between 10 and 20 years earlier than other Australians, the emotional, societal and economic consequences for this population are far greater. Indigenous Australians are also at a particularly high risk of developing psychological illness, given their experience of colonisation, socioeconomic disadvantage, discrimination and racism. It is well-established that depression is an independent risk factor for developing CVD and for poorer outcomes after a CVD event. There is also increasing evidence of causal relationships between psychological distress, depression and CVD in Indigenous communities. These relationships may best be understood within the broader more holistic framework of social and emotional well-being, rather than a biomedical-centred framework that focuses on negative concepts of poor mental health. This chapter explores the complex bidirectional relationship between CVD and depression which is likely to be cyclical in nature and exacerbate the life expectancy gap. Positive approaches to ending this vicious cycle may involve appropriate holistic approaches to measuring and monitoring social and emotional well-being, and acknowledgement of the contribution of intergenerational trauma and discrimination as important determinants of well-being.

Background Microbiota has been linked to the development of multiple cancers through various mechanisms. In bladder cancer (BC), preliminary studies have found alterations in the urinary microbiota of patients with urothelial carcinoma in comparison with healthy individuals. However, the bladder microbiota (BMi) has not been explored. The aims of this study were to characterize the BMi in a cohort of BC patients, to explore differences in the BMi composition between tumor (T) and normal (N) mucosa, and to identify its correlation with clinicopathologic features. Methods A total of 58 samples obtained by cystectomy from 32 BC patients (frozen tumor tissues and normal appearing mucosa for 26 patients and 6 tumor tissues) from Hospital General de Elche Biobank (Spain) were included. DNAs isolated from bladder samples were used to perform 16S rRNA gene sequencing (V3 and V4 region). A paired-end 2 × 300 bp cycle run on Illumina MiSeq. Ribosomal Database Project Classifier was used for taxonomical assignment. Statistical analysis was performed using Rstudio platform. Groups of data were compared using Wilcoxon test and Mann Whitney test for 26T vs 26N (paired group) and 32T vs 26N (unpaired group), respectively. Results There were no statistically significant differences of diversity between T and N, but there were differences of richness between T and N at the genus level (Chao1 index, p = 0.049). Globally, the most abundant phylum was Firmicutes, followed by Bacteroidetes, Proteobacteria and Actinobacteria. We found that the microbial composition differed significantly between T and N in both groups. At the phylum level, while Cyanobacteria.Chloroplast (0.74% vs 2.44%; p = 0.025) was enriched in T, Actinobacteria were reduced in T. Principal component analysis based on the relative abundance of phylum (36.9% PC1 and 28.7% PC2 of explained variance) revealed a significant separation in bacterial community composition between tumor tissues associated with histological tumor grade (permanova grade =0.036). Conclusions Significant differences in the BMi composition associated with tumor grade were observed. Additional studies are needed to determine the role of BMi in the evolution of BC and its therapeutic implications. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

The contribution deals with dry sliding wear behaviour of different Fe–Cr–Mo–[Mn]–[Cu] sintered powder metallurgy systems using a pin on disc test. The effect of chemical composition and two different processing conditions, industrial atmosphere at 1453 K (1180°C) and vacuum atmosphere at 1513 K (1240°C) related to a new proposed type of sinterhardening process, was investigated. The wear phenomena and the wear track characteristics were analysed in relation to processing and microstructures of the tested alloys through light and scanning electron microscopy. A delamination and ploughing wear features were observed for all the sintered steels, and sintering in industrial atmosphere led to an oxidation wear features, too. The results showed positive effect of sinterhardening process via suitable modification of microstructure, and this affected the prior particle boundaries on improving the wear resistance of the tested systems.