Early Impairment of Paracrine and Phenotypic Features in Resident Cardiac Mesenchymal Stromal Cells after Thoracic Radiotherapy.

Radiotherapy-induced cardiac toxicity and consequent diseases still represent potential severe late complications for many cancer survivors who undergo therapeutic thoracic irradiation. We aimed to assess the phenotypic and paracrine features of resident cardiac mesenchymal stromal cells (CMSCs) at early follow-up after the end of thoracic irradiation of the heart as an early sign and/or mechanism of cardiac toxicity anticipating late organ dysfunction. Resident CMSCs were isolated from a rat model of fractionated thoracic irradiation with accurate and clinically relevant heart dosimetry that developed delayed dose-dependent cardiac dysfunction after 1 year. Cells were isolated 6 and 12 weeks after the end of radiotherapy and fully characterized at the transcriptional, paracrine, and functional levels. CMSCs displayed several altered features in a dose- and time-dependent trend, with the most impaired characteristics observed in those exposed in situ to the highest radiation dose with time. In particular, altered features included impaired cell migration and 3D growth and a and significant association of transcriptomic data with GO terms related to altered cytokine and growth factor signaling. Indeed, the altered paracrine profile of CMSCs derived from the group at the highest dose at the 12-week follow-up gave significantly reduced angiogenic support to endothelial cells and polarized macrophages toward a pro-inflammatory profile. Data collected in a clinically relevant rat model of heart irradiation simulating thoracic radiotherapy suggest that early paracrine and transcriptional alterations of the cardiac stroma may represent a dose- and time-dependent biological substrate for the delayed cardiac dysfunction phenotype observed in vivo.

Urethral Stricture Induction Followed by Buccal Mucosa Graft Urethroplasty in a Rat Model.

Urethral reconstruction is an important area of expertise for urologists. The buccal mucosa is considered the best option when urethral grafting is necessary, although in some cases, it is inappropriate or needs to be optimized to repair a given stricture. Therefore, developing innovative procedures and evaluating their putative success in experimental models is crucial to fit the clinical need. With this goal, this study describes a protocol in which urethral stricture was induced by electrocautery in Wistar rats. Urethral reconstruction was performed 1 week later with a buccal mucosa graft, harvested from the lower lip, and placed in a ventral onlay fashion. A retrograde urethrogram showed a significant improvement in urethral diameter after urethroplasty compared to the respective value after stricture induction. Additionally, the graft placement was assessed by blood perfusion analysis using laser Doppler. As expected, a dark blue area corresponded to the non-vascularized buccal mucosa graft. This procedure can successfully simulate the normal pathophysiological process of urethral injury and tissue modulation, as well as urethral reconstruction using a buccal mucosa graft in a reproducible manner, and serve as the basis for future research based on tissue engineering or urethral grafts.

Plant uptake potential and soil persistence of volatile methylsiloxanes in sewage sludge amended soils.

Volatile methylsiloxanes (VMSs) are organosilicon compounds, ubiquitous in modern life. Due to their high use in consumer products, large amounts of these compounds are released into sewer systems, reaching wastewater treatment plants (WWTPs). Its frequent detection in sewage sludge can be of concern when considering its land application, not only due to potential negative impacts on the environment, but also on human health. In this work, the effects of sewage sludge application on plant development and crop productivity were studied, as well as VMSs persistence in the soil and their plant uptake. This study focused on 7 VMSs (D3, D4, D5, D6, L3, L4 and L5) and consisted of a 12-week greenhouse pot experiment, where sewage sludge-amended soils were used to cultivate Pisum sativum (peas). Sewage sludge application to soils had no negative effects on plant development and was tied to crop productivity improvements. Most of the VMSs were still present in soils at the end of the experiment and plant uptake and translocation of the 4 cyclic VMSs (D3, D4, D5, D6) occurred. VMSs were detected in plant tissues up to 161 ± 27 ng g-1 dw (samples of stems, leaves and tendrils), but did not exceed 50 ± 19 ng g-1 dw in peas, which did not translate into a human exposure risk due to ingestion, according to an intake risk assessment. However, soil risk assessments showed that for L5 the hazardous ratios were higher than the threshold value of 1. This means a potential environmental risk despite the low levels of this compound in soils (up to 7.3 ± 0.7 ng g-1 dw). Considering these results, sewage sludge monitoring plans should be defined for VMSs, namely when its final destination is land application, thus allowing a safer management of this residue, taking advantage of its valorization potential.

Uptake and translocation of synthetic musk fragrances by pea plant grown in sewage sludge-amended soils.

Sewage sludges are rich in organic matter and several essential nutrients for plant growth, making them very appealing for application in agricultural soils. However, they may also contain a wide range of emerging pollutants, which has raised concerns about the potential risks of this practice to crops, the environment, and public health - accumulation in soils and/or plant uptake and translocation of contaminants. Therefore, there is a need to study plant-soil interactions and assess the uptake potential of these contaminants by food crops to better understand these risks. The main aim of this work was to assess the possible drawbacks of sludge application to cropland, by observing the impact on the growth and yield of a model crop (pea plant - Pisum sativum) grown over an 86-day greenhouse experiment and by assessing the uptake potential of synthetic musk fragrances. Different sewage sludge application rates (4-30-ton ha-1) and initial concentrations of contaminants were tested. The application of sludge yielded benefits to the cultivated plants, finding improved crop productivity with an application rate of 30-ton ha-1. At the end of the experiment, soil samples and plants separated into sections were analysed using a QuEChERS extraction methodology followed by gas chromatography-mass spectrometry (GC-MS) quantification. Galaxolide (HHCB) and tonalide (AHTN) underwent uptake by the plant roots, having been detected in concentrations up to 346 ng g-1 on a dry weight basis (dw), but only HHCB was detected in above ground tissues. At the end, a decrease in the levels of synthetic musks in the amended soils (>80% in several instances) was observed. Assuming the worst-case scenario, no risk to human health was observed from the ingestion of peas grown on sewage sludge-amended soils. However, a soil hazard quotient analysis yielded worryingly high quotient values for AHTN in nearly all tested conditions.

Molecular Changes In Cardiac Tissue As A New Marker To Predict Cardiac Dysfunction Induced By Radiotherapy.

The contribution of radiotherapy, per se, to late cardiotoxicity remains controversial. To clarify its impact on the development of early cardiac dysfunction, we developed an experimental model in which the hearts of rats were exposed, in a fractionated plan, to clinically relevant doses of ionizing radiation for oncological patients that undergo thoracic radiotherapy. Rat hearts were exposed to daily doses of 0.04, 0.3, and 1.2 Gy for 23 days, achieving cumulative doses of 0.92, 6.9, and 27.6 Gy, respectively. We demonstrate that myocardial deformation, assessed by global longitudinal strain, was impaired (a relative percentage reduction of >15% from baseline) in a dose-dependent manner at 18 months. Moreover, by scanning electron microscopy, the microvascular density in the cardiac apex was significantly decreased exclusively at 27.6 Gy dosage. Before GLS impairment detection, several tools (qRT-PCR, mass spectrometry, and western blot) were used to assess molecular changes in the cardiac tissue. The number/expression of several genes, proteins, and KEGG pathways, related to inflammation, fibrosis, and cardiac muscle contraction, were differently expressed in the cardiac tissue according to the cumulative dose. Subclinical cardiac dysfunction occurs in a dose-dependent manner as detected by molecular changes in cardiac tissue, a predictor of the severity of global longitudinal strain impairment. Moreover, there was no dose threshold below which no myocardial deformation impairment was detected. Our findings i) contribute to developing new markers and exploring non-invasive magnetic resonance imaging to assess cardiac tissue changes as an early predictor of cardiac dysfunction; ii) should raise red flags, since there is no dose threshold below which no myocardial deformation impairment was detected and should be considered in radiation-based imaging and -guided therapeutic cardiac procedures; and iii) highlights the need for personalized clinical approaches.

Presence of metals and metalloids in crumb rubber used as infill of worldwide synthetic turf pitches: Exposure and risk assessment.

Crumb rubber derived from end-of-life tires (ELTs) is frequently used as infill of synthetic turf pitches, promoting circular economy. Although important to reduce the accumulation of waste, the use of recycled ELTs can be a problem to human health and the environment, both by direct contact during pitch use and by the release of these elements to the surroundings, mostly via volatilization and leaching. The present study aimed to evaluate the distribution of metals in ELT-derived crumb rubber collected in artificial turf worldwide and assess possible trends by country, pitch age and type (indoor vs. outdoor). The concentration ranges observed are very wide, especially in outdoor fields and for the most abundant metals, namely Zn (2989-5246 mg/kg), Fe (196-5194 mg/kg), Mg (188-1795 mg/kg) and Al (159-1882 mg/kg). For Zn, the levels were mostly above the safe limits set in European directives for relatable matrices (soils and toy materials), and the same happened for Pb, a much more toxic metal at lower concentrations. A multi-pathway human exposure study was also performed, and the risk assessment shows non-carcinogenic and carcinogenic risks from accidental crumb rubber ingestion (with Cr and Pb as major contributors) above the acceptable values for all the receptors except adult bystanders, with a higher significance to younger individuals. These results bring a different perspective regarding most of the studies reporting low risks related with exposure to metals in crumb rubber.

A first look at the N- and O-glycosylation landscape in anuran skin secretions.

Amphibians secrete a complex array of molecules that shape their interactions with coinhabiting microorganisms and macroscopic predators. Glycans are a rapidly evolving and complex class of biomolecules implicated in intrinsic and extrinsic recognition events. Despite the numerous studies aiming at the biochemical characterization of anuran skin secretions, little is known about protein-linked oligosaccharides, their synthesis pathways, and their homing secreted glycoproteins. In the present report, LC-MS/MS was used to investigate the diversity of N- and O-linked oligosaccharides in the skin secretion of two South American frogs, Pithecopus azureus and Boana raniceps. Additionally, the enzymes responsible for glycan synthesis pathways were evaluated based on their skin tissue transcriptome. Our analyses allowed the annotation of various N- and O-glycan structures commonly found in vertebrate proteins. Paucimannosidic glycans were abundant in the skin secretion of both amphibians; however, hybrid and complex N-glycan structures were detected only in B. raniceps. A good correlation between the structures discovered in glycomic analyses and transcripts encoding enzymes necessary for their synthesis was obtained. Some transcripts such as those of MAN1A2, FUT8, and ST6GALNAC were found solely in B. raniceps. Finally, secreted N- and O- linked glycoproteins were predicted from the transcriptomic data, indicating that proteases and protease inhibitors are putative sources of the glycans described herein. Overall, our results show the presence of oligosaccharides in amphibians skin secretions and suggest that their diversity is species-specific, paving the way for novel perspectives involving amphibian evolution and ecology.

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity.

Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.Trial registration: NCT04370808.

Automatic System for Visual Detection of Dirt Buildup on Conveyor Belts Using Convolutional Neural Networks.

Conveyor belts are the most widespread means of transportation for large quantities of materials in the mining sector. Therefore, autonomous methods that can help human beings to perform the inspection of the belt conveyor system is a major concern for companies. In this context, we present in this work a novel and automatic visual detector that recognizes dirt buildup on the structures of conveyor belts, which is one of the tasks of the maintenance inspectors. This visual detector can be embedded as sensors in autonomous robots for the inspection activity. The proposed system involves training a convolutional neural network from RGB images. The use of the transfer learning technique, i.e., retraining consolidated networks for image classification with our collected images has shown very effective. Two different approaches for transfer learning have been analyzed. The best one presented an average accuracy of 0.8975 with an F-1 Score of 0.8773 for the dirt recognition. A field validation experiment served to evaluate the performance of the proposed system in a real time classification task.

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats.

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional imaging to study the cardiac anatomy of the left ventricle and M-mode echo to assess its dimensions. However, this could limit a comprehensive study. Herein, we describe a protocol that allows an assessment of the heart chamber size, left ventricular function (systolic and diastolic) and valvular function. A conventional medical ultrasound machine was used in this protocol and different echo views were obtained through left parasternal, apical and suprasternal windows. In the left parasternal window, the long and short axis were acquired to analyze left chamber dimensions, right ventricle and pulmonary artery dimensions, and mitral, pulmonary and aortic valve function. The apical window allows the measurement of heart chamber dimensions and evaluation of systolic and diastolic parameters. It also allows Doppler assessment with detection and quantification of heart valve disturbances (regurgitation or stenosis). Different segments and walls of the left ventricle are visualized throughout all views. Finally, the ascending aorta, aortic arch, and descending aorta can be imaged through the suprasternal window. A combination of ultrasound imaging, Doppler flow and tissue Doppler assessment have been obtained to study cardiac morphology and function. This represents an important contribution to improve the assessment of cardiac function in adult rats with impact for research using these animal models.

Marine vegetation analysis for the determination of volatile methylsiloxanes in coastal areas.

Volatile methylsiloxanes (VMSs) are massively produced chemicals that comprise a wide range of industrial and household applications. The presence of cyclic and linear VMSs in several environmental matrices and ecosystems indicates persistence associated with a potential of (bio)accumulation and food web transfer with possible toxicological effects. Due to the high anthropogenic pressure in its vicinities particularly in summer, coastal areas in Southern European countries are potential hotspots for the presence of VMSs. The massive afflux of tourists and consequent increase of the use of personal care products (PCPs) with VMSs in their formulations highlight the importance of VMSs assessment in such areas. In this study, different species of marine vegetation (algae and seaweed) were collected in three different geographical areas, covering the Atlantic Ocean (North coast of Portugal), as well as the Mediterranean Sea (coasts of the Region of Murcia, Spain and of the city of Marseille, France). Samples were analysed for the determination of 4 cyclic (D3, D4, D5, D6) and 3 linear (L3, L4, L5) VMSs employing a QuEChERS extraction methodology, followed by gas chromatography/mass spectrometry (GC/MS) quantification. VMSs were detected in 92% of the 74 samples analysed, with the sum of the concentrations per sample ranging from below the limit of detection (LOD) to 458 ±â€¯26 ng·g-1dw (dry weight). A strong predominance of cyclic VMSs over linear ones was verified in almost all samples studied, with D5 and D6 found at higher concentrations. Seasonal variation was also assessed and despite higher levels of VMSs being identified mostly in summer months, clear seasonal trends were not perceived. It was also noted that generally the higher incidence of VMSs occurred in samples from urban and industrialized areas or in the vicinities of WWTPs, suggesting a direct input from these sources in the levels of siloxanes observed.

Discontinuity Detection in the Shield Metal Arc Welding Process.

This work proposes a new methodology for the detection of discontinuities in the weld bead applied in Shielded Metal Arc Welding (SMAW) processes. The detection system is based on two sensors-a microphone and piezoelectric-that acquire acoustic emissions generated during the welding. The feature vectors extracted from the sensor dataset are used to construct classifier models. The approaches based on Artificial Neural Network (ANN) and Support Vector Machine (SVM) classifiers are able to identify with a high accuracy the three proposed weld bead classes: desirable weld bead, shrinkage cavity and burn through discontinuities. Experimental results illustrate the system's high accuracy, greater than 90% for each class. A novel Hierarchical Support Vector Machine (HSVM) structure is proposed to make feasible the use of this system in industrial environments. This approach presented 96.6% overall accuracy. Given the simplicity of the equipment involved, this system can be applied in the metal transformation industries.

Anger and stroke: a potential association that deserves serious consideration.

OBJECTIVE: To assess the relationship between states of anger and stroke. METHODS: Systematic review of the literature. RESULTS: In total, 21 papers were selected for the systematic review of data published on the subject of anger and stroke. A state of anger may be a risk factor for stroke, as well as a consequence of brain lesions affecting specific areas that are caused by a stroke. Scales to assess anger varied among authors. There was no consensus regarding the area of brain lesions that might lead to a state of anger. Although some authors agreed that lesions on the right side led to angrier behaviour, others found that lesions on the left side were more relevant to anger. Likewise, there was no consensus regarding the prevalence of anger pre or post-stroke. Some authors did not even find that these two conditions were related. CONCLUSION: Although most authors have accepted that there is a relationship between anger and stroke, studies with uniform methodology need to be conducted if this association is to be properly evaluated and understood.

Carnival or football, is there a real risk for acquiring dengue fever in Brazil during holidays seasons?

More than 600,000 football fans, coming from all over the world, were expected to visit Brazil during the FIFA World Cup 2014. International travel can become a public health problem when the visitors start to become sick, needing medical intervention and eventually hospitalization. The occurrence of dengue fever infections in Brazil is persistent and has been increasing since the 1980s, and the health authorities were expected to take preventive measures and to warn the visitors about the risks during the tournament period. Before the World Cup started, studies have been published stating that dengue could be a significant problem in some of the Brazilian cities hosting the games. These conclusions were taken after a brief observation of the available data, analyzing its mean and standard deviation only, or based on seasonal climate forecasts, causing alarm for the world cup in Brazil. Here, with a more careful data analysis, we show that the seasonality of the disease plays a major role in dengue transmission. The density of dengue cases in Brazil is residual during winter in the Southern hemisphere (mid June to mid September) and the fans of football were not likely to get dengue during the tournament period.

Understanding the effect of vector dynamics in epidemic models using center manifold analysis.

In vector borne diseases the human hosts' epidemiology often acts on a much slower time scales than the one of the mosquitos which transmit the disease as a vector from human to human, due to their vastly different life cycles. We investigate in a model with susceptible (S), infected (I) and recovered (R) humans and susceptible (U) and infected (V) mosquitoes in how far the fast time scale of the mosquito epidemiology can be slaved by the slower human epidemiology, so that for the understanding of human disease data mainly the dynamics of the human time scale is essential and only slightly perturbed by the mosquito dynamics. This analysis of the SIRUV model is qualitatively in agreement with a previously investigated simpler SISUV model, hence a feature of vector-borne diseases in general.

Desempenho e desenvolvimento corporal de bovinos leiteiros mestiços submetidos a níveis de suplementação em pastagem de Brachiaria brizantha / Performance and body development crossbred dairy cattle submitted to levels of supplementation in Brachiaria brizantha

Estudou-se o efeito dos níveis de suplementação energética, em pastagem de Brachiaria brizantha, sobre o desempenho e o desenvolvimento de medidas corporais de bovinos mestiços de origem leiteira na fase de desenvolvimento inicial. O experimento foi conduzido em 126 dias, divididos em seis períodos de 21 dias, correspondendo a segunda metade do período de chuvas e início do período seco. Foram utilizados 24 bovinos mestiços não castrados Holandês/Zebu, com 6 meses de idade e 118±16kg de peso vivo no início do experimento. Os tratamentos foram determinados pelo fornecimento de suplemento energético em quantidade equivalente a 0,5 ou 1,0 por cento do peso vivo. Constatou-se interação significativa entre os tratamentos e períodos experimentais sobre o ganho em peso médio diário. Animais do grupo de alto nível de suplementação (NA) mantiveram o GMD mais elevado e mais constante com a evolução dos períodos (0,95; 1,09; 1,07; 1,00; 0,93 e 0,23kg dia-1), resultando em maior peso final (231,26 vs 197,55kg), enquanto que os animais do tratamento de médio nível de suplementação (NM) apresentaram maiores oscilações de GMD entre os períodos (0,83; 0,59; 0,75; 0,78; 0,44 e 0,35kg dia-1). O grupo NA apresentou maiores patamares para as medidas finais (cm) de perímetro torácico (146,02 vs 136,44); comprimento (108,35 vs 103,22); altura da garupa (120,38 vs 112,46); altura da cernelha (113,91 vs 110,62) e não diferiu quanto ao perímetro escrotal e de canela.

It was studied the effect of energy supplementation levels in Brachiaria brizantha on performance and development of body measurements in crossbred dairy cattle at early growth stages. The experiment was conducted in 126 days, divided into six periods of 21 days, corresponding to the second half of the rainy season and early dry season. It was used 24 crossbred non-castrated Holstein / Zebu, with 6 months of age and 118±16kg live weight at the start of the experiment. Treatments were determined by the supply of energy supplement in an amount equivalent to 0.5 or 1.0 percent of body weight. It was found a significant interaction between treatments and experimental periods on the average daily weight gain. Animals with high level of supplementation (NA) had the highest and more constants ADG with the elapsing periods (0.95, 1.09, 1.07, 1.00, 0.93 and 0.23kg days-1), resulting in higher final weight (231.26 vs. 197.55kg), while animals fed with the medium level of supplementation ( NM) had higher ADG oscillations between periods (0.83, 0.59, 0.75, 0.78, 0.44 and 0.35kg day-1). The NA group showed higher final measures (cm) of girth (146.02 vs 136.44), length (108.35 vs 103.22), croup height (120.38 vs. 112.46), withers height (113.91 vs 110.62) and did not differ for scrotal circumference and cinnamon.