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In this study, the effect of the size of SiC particle on high temperature damping capacity and dynamic Young's modulus of hot-pressed AlSi-SiC composites has been investigated. SiC particles with sizes of 13 µm, 38.8 µm and 118 µm were added to AlSi matrix to prepare the hot-pressed AlSi-SiC composites. These composites were characterized using a dynamic mechanical analyser (DMA), over a temperature range of room temperature to 400 °C. Regarding damping capacity, all AlSi-SiCp composites exhibited higher damping capacity compared to unreinforced AlSi alloy (for all tested frequencies). AlSi-SiCp(118) composites exhibited the highest improvement in damping capacity. A damping peak was observed near 250 °C, as a result of a relaxation process. Regarding dynamic Young's modulus, it was observed that the addition of SiCp to the AlSi alloy improved the Young's modulus. It was also demonstrated that by increasing the SiCp size, a decrease in Young's modulus is attained, with the highest improvement in dynamic Young's modulus being obtained by AlSi-SiCp(13) composite. [ABSTRACT FROM AUTHOR]

Aim: Lumbar spondylolisthesis is a common cause of disabling leg and back pain. A detailed preoperative radiological evaluation is essential to define the best surgical approach, such as the need for instrumentation or simple neurological decompression. The objective of this study is to correlate the main findings in lumbar X-ray, MRI and to identify factors that determine instability., Material and Methods: Retrospective and observational study of patients with confirmed diagnosis of lumbar or lumbosacral low grade spondylolisthesis at a single level. Preoperative X-ray and MRI were evaluated. Statistical analysis was performed using Fisher\'s exact test and Kappa statistics., Results: 59 patients were included. 62% of the patients had Modic changes in the MRI. Degenerative and isthmic spondylolisthesis was found in 49.2% and 50.8, respectively. All patients had degenerative disc changes at the level of the listesis. 18 (30,5%) and 3 (5,1%) patients had moderately and severely asymmetrical facets, respectively. 64,4% had neutral facets. Dynamic X-ray detected mobility in 52.5% of the cases. There was a negative correlation between the presence of tropism, mobility (p = 0.03) and present facet tropism (p = 0.02). Substantial agreement (91.52%) between MRI and X-ray was found [Kappa 0,81 (0,66;0,97)]., Conclusion: MRI was sufficient for the diagnosis of lumbar spondylolisthesis and dynamic lumbar Rx was important to define segmental mobility. In addition, facet tropism had a protective effect for instability.

Brain glucose hypometabolism and insulin alterations are common features of many neurological diseases. Herein we sought to corroborate the brain glucose hypometabolism that develops with ageing in 12-months old Tau-VLW transgenic mice, a model of tauopathy, as well as to determine whether this model showed signs of altered peripheral glucose metabolism. Our results demonstrated that 12-old months Tau mice exhibited brain glucose hypometabolism as well as basal hyperglycemia, impaired glucose tolerance, hyperinsulinemia, and signs of insulin resistance. Then, we further studied the effect of chronic metformin treatment (9 months) in Tau-VLW mice from 9 to 18 months of age. Longitudinal PET neuroimaging studies revealed that chronic metformin altered the temporal profile in the progression of brain glucose hypometabolism associated with ageing. Besides, metformin altered the content and/or phosphorylation of key components of the insulin signal transduction pathway in the frontal cortex leading to significant changes in the content of the active forms. Thus, metformin increased the expression of pAKT-Y474 while reducing pmTOR-S2448 and pGSK3β. These changes might be related, at least partially, to a slow progression of ageing, neurological damage, and cognitive decline. Metformin also improved the peripheral glucose tolerance and the ability of the Tau-VLW mice to maintain their body weight through ageing. Altogether our study shows that the tau-VLW mice could be a useful model to study the potential interrelationship between tauopathy and central and peripheral glucose metabolism alterations. More importantly our results suggest that chronic metformin treatment may have direct beneficial central effects by post-transcriptional modulation of key components of the insulin signal transduction pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: to present a 12-month follow-up with photographic and tomographic analyses of the effect of polymethyl methacrylate-based bone cement graft (PMMA) in gingival exposure (GE) in patients with excessive gingival display (EGD)., Methods: Twelve patients with EGD were included. The PMMA was surgically placed. A frontal and lateral photograph protocol was performed at baseline (T 0 ), 3 (T 3 ), 6 (T 6 ), and 12 months (T 12 ) post-operatively. Soft tissue cone-beam computed tomography (ST-CBCT) was performed at T 0 and T 12 . Measures included GE, length of the lip vermilion (LLV), lip shape (LS), nose width (NW), filter width (FW), nasolabial angle (NAS) while smiling, and nasolabial angle at rest (NAR). The height, thickness, and volume of the cement graft were also measured in the ST-CBCT. The comparisons were performed by Kruskal-Wallis test at 5 % of significance (p < 0.05)., Results: The height, thickness, and volume of the PMMA were respectively 12.84 ± 1.59 mm, 3.83 ± 0.53, and 1532.02 ± 532.52 mm 3 . PMMA significantly decreased GE from 8.33 ± 1.25 mm (T 0 ) to 6.60 ± 0.93 mm (T 12 ) (p < 0.01). NAR was 98.34 ± 9.28° at T 0 and increased to 105.13 ± 7.33° at T 12 ; however, the angle value was not statistically different (p = 0.08). LLV, LS, NW, FW, and NAS did not exhibit statistical differences between the baseline and follow-up periods., Conclusions: PMMA significantly decreased GE in a 12-month follow-up without influencing adjacent soft tissue anatomical structures., Competing Interests: Authors declare no conflict of interest., (© 2024 The Authors.)

Several neurological diseases share pathological alterations, even though they differ in their etiology. Neuroinflammation, altered brain glucose metabolism, oxidative stress, mitochondrial dysfunction and amyloidosis are biological events found in those neurological disorders. Altered insulin-mediated signaling and brain glucose hypometabolism are characteristic signs observed in the brains of patients with certain neurological diseases, but also others such as type 2 diabetes mellitus and vascular diseases. Thus, significant reductions in insulin receptor autophosphorylation and Akt kinase activity, and increased GSK-3 activity and insulin resistance, have been reported in these neurological diseases as contributing to the decline in cognitive function. Supporting this relationship is the fact that nasal and hippocampal insulin administration has been found to improve cognitive function. Additionally, brain glucose hypometabolism precedes the unmistakable clinical manifestations of some of these diseases by years, which may become a useful early biomarker. Deficiencies in the major pathways of oxidative energy metabolism have been reported in patients with several of these neurological diseases, which supports the hypothesis of their metabolic background. This review remarks on the significance of insulin and brain glucose metabolism alterations as keystone common pathogenic substrates for certain neurological diseases, highlighting new potential targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Blázquez, Hurtado-Carneiro, LeBaut-Ayuso, Velázquez, García-García, Gómez-Oliver, Ruiz-Albusac, Ávila and Pozo.)

Background: There has been a significant increase in number of patients seeking neuropsychological rehabilitation months after the acute phase of COVID-19 infection., Objective: Identify the cognitive and psychiatric disorders in patients with long COVID or Post-Acute Sequelae of COVID (PASC) and explore the association between disease severity during the acute phase and persistent neuropsychological manifestations., Methods: 614 adults were assessed an average of eight months post-infection. Participants were, on average, 47.6 y.o., who sought rehabilitation for neuropsychological problems. Patients were evaluated using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), Phonemic Verbal Fluency and Clock Drawing tests (NEUPSILIN) for executive functions, and the Hospital Anxiety and Depression Scale (HADS)., Results: The BNIS score was significantly below reference values in all subscales, especially affect and memory. Verbal Fluency and Clock Drawing subtest results were also lower. Patients with PASC tested high for anxiety/depression, but there was no statistically significant relationship between HADS and BNIS scores. Neuropsychological evaluations showed no differences in cognitive or psychiatric profiles between hospitalized and non-hospitalized patients., Conclusions: Neuropsychological results suggest executive function problems and high incidence of anxiety/depression, irrespective of acute-phase severity, underscoring a need for neurorehabilitation programs while providing data for public policy initiatives.

The liver's high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant's effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.

Introduction Meningiomas are slow-growing intracranial neoplasms that originate from arachnoid meningothelial cells and represent 13-26% of intracranial tumors, thus being the most common. There are numerous technological advances available for a better understanding of the molecular pathways correlated with tumorigenesis and tumor progression of meningiomas. In this context, the role of microRNAs (miRNAs), which are non-coding RNAs (ncRNAs) consisting of 18 to 25 nucleotides whose function is the silencing of mRNA at the posttranscriptional level, has been highlighted. Recent studies suggest that miRNAs may act as possible biomarkers as well as therapeutic targets for various diseases, including brain tumors. Therefore, the objective of our study was to evaluate the tissue and plasma expression of the miRNAs miR-181d, miR-181c, and miR-130a. Methods The miRNAs miR-181d, miR-181c, and miR-130a were selected from our group's prior study by the large-scale microarray analysis technique. In this work, the expression of these miRNAs in the tumor tissue and plasma of patients with grade I (16 patients), II (16 patients), and III (eight patients) meningiomas was evaluated. Results MiR-181d was overexpressed in both tumor tissue and plasma in the studied groups. The level of expression was higher according to the progression of tumor grade. MiR-181c and miR-130a showed no significant difference in the studied groups in either tumor tissue or plasma. Conclusions MiR-181d has potential as a biomarker for meningiomas and is associated with the tumor progression of meningiomas., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Carneiro et al.)

Glucagon-like peptide 1 (GLP-1) and PAS kinase (PASK) control glucose and energy homeostasis according to nutritional status. Thus, both glucose availability and GLP-1 lead to hepatic glycogen synthesis or degradation. We used a murine model to discover whether PASK mediates the effect of exendin-4 (GLP-1 analogue) in the adaptation of hepatic glycogen metabolism to nutritional status. The results indicate that both exendin-4 and fasting block the Pask expression, and PASK deficiency disrupts the physiological levels of blood GLP1 and the expression of hepatic GLP1 receptors after fasting. Under a non-fasted state, exendin-4 treatment blocks AKT activation, whereby Glucokinase and Sterol Regulatory Element-Binding Protein-1c (Srebp1c) expressions were inhibited. Furthermore, the expression of certain lipogenic genes was impaired, while increasing Glucose Transporter 2 (GLUT2) and Glycogen Synthase (GYS). Moreover, exendin-4 treatment under fasted conditions avoided Glucose 6-Phosphatase (G6pase) expression, while maintaining high GYS and its activation state. These results lead to an abnormal glycogen accumulation in the liver under fasting, both in PASK-deficient mice and in exendin-4 treated wild-type mice. In short, exendin-4 and PASK both regulate glucose transport and glycogen storage, and some of the exendin-4 effects could therefore be due to the blocking of the Pask expression.

The protein kinase with PAS domains (PASK) is a nutrient and energy sensor located in the cells of multiple organs. Many of the recent findings for understanding PASK functions in mammals have been reported in studies involving PASK-deficient mice. This minireview summarizes the PASK role in the control of fasting and feeding responses, focusing especially on the hypothalamus and liver. In 2013, PASK was identified in the hypothalamic areas involved in feeding behavior, and its expression was regulated under fasting/refeeding conditions. Furthermore, it plays a role in coordinating the activation/inactivation of the hypothalamic energy sensors AMPK and mTOR/S6K1 pathways in response to fasting. On the other hand, PASK deficiency prevents the development of obesity and non-alcoholic fatty liver in mice fed with a high-fat diet. This protection is explained by the re-establishment of several high-fat diet metabolic alterations produced in the expression of hepatic transcription factors and key enzymes that control the main metabolic pathways involved in maintaining metabolic homeostasis in fasting/feeding responses. This minireview covers the effects of PASK inactivation in the expression of certain transcription factors and target enzymes in several metabolic pathways under situations such as fasting and feeding with either a standard or a high-fat diet., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Hurtado-Carneiro, Pérez-García, Alvarez and Sanz.)

Introduction: Scientific evidence regarding children's understanding of the concept of death is scarce. This has recently been pointed out by the International Children's Palliative Care Network as a priority area of research. In particular, the avoidance of emotion in this area of research is an important shortcoming. This study aims to develop an in-depth view of the emotional dimension of the child's understanding of death, also seeking to relate it to the cognitive dimension., Material and Methods: We interviewed children (three to six years old) using a book illustrating a hypothetical scenario in which a child faced the death of a relative. We asked questions to assess the cognitive subconcepts of death and the emotional dimension (what the child would feel and what parents should say)., Results: Of the 54 participants, the majority said that the child would feel sad (n = 46, 85%) and that parents should inform her/him (n = 47, 87%); these responses did not vary significantly with age. The cognitive understanding of the concept of death in children who reported sadness was significantly higher., Discussion: Even the youngest children feel death, and it is not possible to disconnect cognitive and emotional understanding. Additionally, children should be informed in order to foster a proper and multidimensional elaboration of death., Conclusion: This study provides valuable information to health professionals and other interested adults about the way preschoolers position themselves in relation to death.

The relative simplicity of IoT networks extends service vulnerabilities and possibilities to different network failures exhibiting system weaknesses. Therefore, having a dataset with a sufficient number of samples, labeled and with a systematic analysis, is essential in order to understand how these networks behave and detect traffic anomalies. This work presents DAD: a complete and labeled IoT dataset containing a reproduction of certain real-world behaviors as seen from the network. To approximate the dataset to a real environment, the data were obtained from a physical data center, with temperature sensors based on NFC smart passive sensor technology. Having carried out different approaches, performing mathematical modeling using time series was finally chosen. The virtual infrastructure necessary for the creation of the dataset is formed by five virtual machines, a MQTT broker and four client nodes, each of them with four sensors of the refrigeration units connected to the internal IoT network. DAD presents a seven day network activity with three types of anomalies: duplication, interception and modification on the MQTT message, spread over 5 days. Finally, a feature description is performed, so it can be used for the application of the various techniques of prediction or automatic classification.

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors., Competing Interests: The authors have declared that no competing interests exist.

Several signaling pathways may be affected during aging. All are regulated by nutrient levels leading to a decline in mitochondrial function and autophagy and to an increase in oxidative stress. PAS Domain Kinase (PASK) is a nutrient and bioenergetic sensor. We have previously found that PASK plays a role in the control of hepatic metabolic balance and mitochondrial homeostasis. To investigate PASK's role in hepatic oxidative stress during aging, we analyzed the mitochondrial function, glucose tolerance, insulin resistance, and lipid-related parameters in aged PASK-deficient mice. Hepatic Pask mRNA decreased in step with aging, being undetectable in aged wild-type (WT) mice. Aged PASK-deficient mice recorded lower levels of ROS/RNS compared to aged WT. The regulators of mitochondrial biogenesis, PGC1a, SIRT1 and NRF2, decreased in aged WT, while aged PASK-deficient mice recorded a higher expression of NRF2, GCLm and HO1 proteins and CS activity under fasted conditions. Additionally, aged PASK-deficient mice recorded an overexpression of the longevity gene FoxO3a , and maintained elevated PCNA protein, suggesting that hepatic cell repair mechanisms might be functional. PASK-deficient mice have better insulin sensitivity and no glucose intolerance, as confirmed by a normal HOMA-IR index. PASK may be a good target for reducing damage during aging.

Collaborative Filtering algorithms provide users with recommendations based on their opinions, that is, on the ratings given by the user for some items. They are the most popular and widely implemented algorithms in Recommender Systems, especially in e-commerce, considering their good results. However, when the information is extremely sparse, independently of the domain nature, they do not present such good results. In particular, it is difficult to offer recommendations which are accurate enough to a user who has just arrived to a system or who has rated few items. This is the well-known new user problem, a type of cold-start. Profile Expansion techniques had been already presented as a method to alleviate this situation. These techniques increase the size of the user profile, by obtaining information about user tastes in distinct ways. Therefore, recommender algorithms have more information at their disposal, and results improve. In this paper, we present the High Order Profile Expansion techniques, which combine in different ways the Profile Expansion methods. The results show 110% improvement in precision over the algorithm without Profile Expansion, and 10% improvement over Profile Expansion techniques., Competing Interests: The authors have declared that no competing interests exist.

Primary retroperitoneal mucinous cystic neoplasms (PRMCN) with borderline malignancy are exceptionally rare tumours with lack of pathognomonic clinical and imaging-specific features. Here, we report a case of PRMCN with borderline malignancy in a 62-year-old woman who presented with abdominal pain. Imaging studies revealed a well-defined cystic mass on the right flank in close relation with the cecum and caecal appendix, without other findings suggestive of malignancy. A possible diagnosis of an ovarian epithelial tumour was ruled out intraoperatively. After surgical excision, microscopic examination allowed the final diagnosis. As there is no evidence of disease during follow-up, complete tumour resection without cystic rupture appears to be the best therapeutic option. Thus, although rare, this tumour should be considered when imaging findings suggest an ovarian mucinous neoplasm in women with normal ovaries. An international registry for rare tumours and longer follow-ups may contribute for more consistent approach for managing these patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Major depressive disorder (MDD) or depression is among the most prevalent psychiatric disorders, affecting more than 300 million people globally. Early detection is critical for rapid intervention, which can potentially reduce the escalation of the disorder., Objective: This study used data from social media networks to explore various methods of early detection of MDDs based on machine learning. We performed a thorough analysis of the dataset to characterize the subjects' behavior based on different aspects of their writings: textual spreading, time gap, and time span., Methods: We proposed 2 different approaches based on machine learning singleton and dual. The former uses 1 random forest (RF) classifier with 2 threshold functions, whereas the latter uses 2 independent RF classifiers, one to detect depressed subjects and another to identify nondepressed individuals. In both cases, features are defined from textual, semantic, and writing similarities., Results: The evaluation follows a time-aware approach that rewards early detections and penalizes late detections. The results show how a dual model performs significantly better than the singleton model and is able to improve current state-of-the-art detection models by more than 10%., Conclusions: Given the results, we consider that this study can help in the development of new solutions to deal with the early detection of depression on social networks., (©Fidel Cacheda, Diego Fernandez, Francisco J Novoa, Victor Carneiro. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 10.06.2019.)

Periodontitis is an infectious and inflammatory disease of high prevalence worldwide and constitutes a significant oral health problem. It can lead to tooth loss. In addition, the local inflammatory process can cause the release of inflammatory mediators in the bloodstream and, consequently, contribute to the emergence of systemic effects as cardiovascular and diabetic complications. The purpose of this mini review is to alert health professionals about the risk that periodontitis represents for the onset or exacerbation of complications in individuals with type 2 diabetes mellitus and to emphasize that the mechanical treatment of periodontal disease and reestablishment of oral health are essential for the metabolic control of these patients. The periodontal therapy may help to reduce the risk of systemic complications in diabetes patients. Proper dental management should be suggested by health professionals, mainly from physicians to their patients, in order to improve the health conditions in these individuals.

Surgical management in epithelial ovarian cancer (EOC) has a significant impact in overall survival and progression-free survival. The Brazilian Society of Surgical Oncology (BSSO) supported a taskforce of experts to reach a consensus: experienced and specialised trained surgeons, in cancer centres, provide the best EOC surgery. Laparoscopic and/or radiological staging prognosticates the possibility of complete cytoreduction (CC0) and helps to reduce unnecessary laparotomies. Surgical techniques were reviewed. Multidisciplinary input is essential for treatment planning. Quality assurance criteria are proposed and require national consensus. Genetic testing is mandatory. This consensus states the final recommendations from BSSO for management of EOC., Tweetable Abstract: Brazilian Society of Surgical Oncology consensus for surgery in epithelial ovarian cancer patients., (© 2018 Royal College of Obstetricians and Gynaecologists.)

The prevalence of overweight and obesity in the population, along with their associated complications, is a major factor contributing to increased morbidity and mortality in developed countries. The liver is a vital organ for maintaining metabolic homeostasis, especially in the adjustment periods in fasting and feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy metabolism in response to nutritional status. PASK-deficient mice with a high-fat diet (HFD) resist the development of obesity and hepatic steatosis, with improved insulin sensitivity. We have investigated the regulation of the PASK expression in an HFD, as well as its role in adapting to fasting and feeding conditions. PASK-deficient mice with an HFD record improved parameters for the following: body weight, glucose tolerance, insulin resistance and serum lipid parameters. An HFD alters the down-regulation of Pask expression produced by fasting, as normally happens in a standard-fat diet. PASK deficiency blocks or diminishes the expression of many genes overexpressed in HFD-fed mice, such as the following: transcription factors involved in the regulation of gluconeogenic enzymes, the transport of fatty acid into mitochondria, beta-oxidation and de novo lipogenesis. PASK also regulates gene expression posttranscriptionally through the short noncoding RNAs involved in lipid metabolism and glucose homeostasis. The expression of miR-33a and miR-143 changes in PASK-deficient mice with an HFD. Thus, PASK-deficient mice improved their adaptation to feeding/fasting through a highly regulated molecular mechanism that controls the expression and function of the transcription factors, enzymes and miRNAs involved in glucose and insulin signaling., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Classification using a scale of visual notes is a strategy used to select erect bean plants in order to improve bean plant architectures. Use of morphological traits associated with the phenotypic expression of bean architecture in classification procedures may enhance selection. The objective of this study was to evaluate the potential of artificial neural networks (ANNs) as auxiliary tools in the improvement of bean plant architecture. Data from 19 lines were evaluated for 22 traits, in 2007 and 2009 winter crops. Hypocotyl diameter and plant height were selected for analysis through ANNs. For classification purposes, these lines were separated into two groups, determined by the plant architecture notes. The predictive ability of ANNs was evaluated according to two scenarios to predict the plant architecture - training with 2007 data and validating in 2009 data (scenario 1), and vice versa (scenario 2). For this, ANNs were trained and validated using data from replicates of the evaluated lines for hypocotyl diameter individually, or together with the mean height of plants in the plot. In each scenario, the use of data from replicates or line means was evaluated for prediction through previously trained and validated ANNs. In both scenarios, ANNs based on hypocotyl diameter and mean height of plants were superior, since the error rates obtained were lower than those obtained using hypocotyl diameter only. Lower apparent error rates were verified in both scenarios for prediction when data on the means of the evaluated traits were submitted to better trained and validated ANNs.

Background: This study compared the use of static cold storage versus continuous hypothermic machine perfusion in a cohort of kidney transplant recipients at high risk for delayed graft function (DGF)., Methods: In this national, multicenter, and controlled trial, 80 pairs of kidneys recovered from brain-dead deceased donors were randomized to cold storage or machine perfusion, transplanted, and followed up for 12 months. The primary endpoint was the incidence of DGF. Secondary endpoints included the duration of DGF, hospital stay, primary nonfunction, estimated glomerular filtration rate, acute rejection, and allograft and patient survivals., Results: Mean cold ischemia time was high but not different between the 2 groups (25.6 ± 6.6 hours vs 25.05 ± 6.3 hours, 0.937). The incidence of DGF was lower in the machine perfusion compared with cold storage group (61% vs. 45%, P = 0.031). Machine perfusion was independently associated with a reduced risk of DGF (odds ratio, 0.49; 95% confidence interval, 0.26-0.95). Mean estimated glomerular filtration rate tended to be higher at day 28 (40.6 ± 19.9 mL/min per 1.73 m 2 vs 49.0 ± 26.9 mL/min per 1.73 m 2 ; P = 0.262) and 1 year (48.3 ± 19.8 mL/min per 1.73 m 2 vs 54.4 ± 28.6 mL/min per 1.73 m 2 ; P = 0.201) in the machine perfusion group. No differences in the incidence of acute rejection, primary nonfunction (0% vs 2.5%), graft loss (7.5% vs 10%), or death (8.8% vs 6.3%) were observed., Conclusions: In this cohort of recipients of deceased donor kidneys with high mean cold ischemia time and high incidence of DGF, the use of continuous machine perfusion was associated with a reduced risk of DGF compared with the traditional cold storage preservation method., Competing Interests: The authors declare no funding or conflicts of interest.

In a primary education classroom of any country, children of the same age have very different statures, reaching variations of 200 mm (Gonçalves, 2012). However, the school furniture provided is not suitable or adaptable to these differences. Designing school furniture able to respond to these variations is, therefore, a challenge for ergonomics and design in a global market. It is clearly not viable for industries to adapt productions for each country. When competitiveness and limitation of resources are essential for the viability of any product it becomes essential to find a universal system adapted to the requisites of any country. Taking as prescription measure the popliteal height obtained from the data of different countries, a universal measurement system for the school chair and desk set is proposed, combining the ellipse methodology used by Molenbroek et al. (2003) and the (mis)match equations mentioned by Castellucci et al. (2014b). From the results obtained, it can be concluded that only 5 sizes are needed to implement this new measurement system of evolutionary school furniture for the primary education classroom., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Artificial neural networks have shown great potential when applied to breeding programs. In this study, we propose the use of artificial neural networks as a viable alternative to conventional prediction methods. We conduct a thorough evaluation of the efficiency of these networks with respect to the prediction of breeding values. Therefore, we considered eight simulated scenarios, and for the purpose of genetic value prediction, seven statistical parameters in addition to the phenotypic mean in a network designed as a multilayer perceptron. After an evaluation of different network configurations, the results demonstrated the superiority of neural networks compared to estimation procedures based on linear models, and indicated high predictive accuracy and network efficiency.

Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta-lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n=134), their owners (n=134), and humans who claim to have no contact with dogs (n=44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed-field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains., (Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Objective: This paper aimed to analyze the in vitro industrialized fruit juices effect plus soy to establish the erosive potential of these solutions., Materials and Methods: Seventy bovine incisors were selected after being evaluated under stereomicroscope. Their crowns were prepared and randomly divided into 7 groups, using microhardness with allocation criteria. The crowns were submitted to the fruit juice plus soy during 15 days, twice a day. The pH values, acid titration, and Knoop microhardness were recorded and the specimens were evaluated using X-ray microfluorescence (µXRF)., Results: The pH average for all juices and after 3 days was significantly below the critical value for dental erosion. In average, the pH value decreases 14% comparing initial time and pH after 3 days. Comparing before and after, there was a 49% microhardness decrease measured in groups (p < 0.05). Groups G1, G2, G5, and G6 are above this average. The analysis by μXRF showed a decrease of approximately 7% Ca and 4% P on bovine crowns surface. Florida (FL) statistical analysis showed a statistically significant 1 difference between groups. Thus, a tooth chance to suffer demineralization due to industrialized fruit juices plus soy is real.

This study aimed to investigate the effects of nonsurgical periodontal therapy on white blood cell (WBC) count and levels of transforming growth factor beta (TGF&mdash;&#946;) in serum from subjects with severe periodontitis. Serum from 28 subjects with periodontitis (mean age: 34.36±6.24; 32% men) and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to therapy. Blood samples were obtained from 23 subjects who completed therapy (9&mdash;12 months). A well&mdash;controlled periodontal treatment protocol was established in three stages: mechanical periodontal therapy (scaling and root planning), reinstrumentation of dental sites, and supportive periodontal therapy. Periodontal and systemic parameters such as the total number of WBCs and TGF&mdash;&#946; levels, accessed by enzyme&mdash;linked immunosorbent assay (ELISA), were included. After therapy, all clinical periodontal parameters decreased (p&lt;0.0001). There were no statistical differences in WBC count between experimental and control groups before or after therapy. However, after therapy, the mean value of lymphocytes in patients with localized aggressive periodontitis (LAgP) was statistically higher than that of patients with generalized chronic periodontitis (GCP) (p&lt;0.0357). Additionally, TGF&mdash;&#946; levels in LAgP and GCP patients were higher compared to controls before therapy (p&lt;0.05 and p&lt;0.01, respectively). In LAgP patients, periodontal therapy was associated with increased number of lymphocytes.

Although the brain has been considered an insulin-insensitive organ, recent reports on the location of insulin and its receptors in the brain have introduced new ways of considering this hormone responsible for several functions. The origin of insulin in the brain has been explained from peripheral or central sources, or both. Regardless of whether insulin is of peripheral origin or produced in the brain, this hormone may act through its own receptors present in the brain. The molecular events through which insulin functions in the brain are the same as those operating in the periphery. However, certain insulin actions are different in the central nervous system, such as hormone-induced glucose uptake due to a low insulin-sensitive GLUT-4 activity, and because of the predominant presence of GLUT-1 and GLUT-3. In addition, insulin in the brain contributes to the control of nutrient homeostasis, reproduction, cognition, and memory, as well as to neurotrophic, neuromodulatory, and neuroprotective effects. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes mellitus (T2DM), and Alzheimer's disease (AD). A close association between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients, and some authors have proposed the name "type 3 diabetes" for this association. There are links between AD and T2DM through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein O-GlcNAcylation, formation of amyloid plaques, altered Aβ metabolism, and tau hyperphosphorylation. Advances in the knowledge of preclinical AD and T2DM may be a major stimulus for the development of treatment for preventing the pathogenic events of these disorders, mainly those focused on reducing brain insulin resistance, which is seems to be a common ground for both pathological entities.

The complications caused by overweight, obesity and type 2 diabetes are one of the main problems that increase morbidity and mortality in developed countries. Hypothalamic metabolic sensors play an important role in the control of feeding and energy homeostasis. PAS kinase (PASK) is a nutrient sensor proposed as a regulator of glucose metabolism and cellular energy. The role of PASK might be similar to other known metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). PASK-deficient mice resist diet-induced obesity. We have recently reported that AMPK and mTOR/S6K1 pathways are regulated in the ventromedial and lateral hypothalamus in response to nutritional states, being modulated by anorexigenic glucagon-like peptide-1 (GLP-1)/exendin-4 in lean and obese rats. We identified PASK in hypothalamic areas, and its expression was regulated under fasting/re-feeding conditions and modulated by exendin-4. Furthermore, PASK-deficient mice have an impaired activation response of AMPK and mTOR/S6K1 pathways. Thus, hypothalamic AMPK and S6K1 were highly activated under fasted/re-fed conditions. Additionally, in this study, we have observed that the exendin-4 regulatory effect in the activity of metabolic sensors was lost in PASK-deficient mice, and the anorexigenic properties of exendin-4 were significantly reduced, suggesting that PASK could be a mediator in the GLP-1 signalling pathway. Our data indicated that the PASK function could be critical for preserving the nutrient effect on AMPK and mTOR/S6K1 pathways and maintain the regulatory role of exendin-4 in food intake. Some of the antidiabetogenic effects of exendin-4 might be modulated through these processes.

Gorlin-Goltz syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), is a rare autosomal dominant disorder caused by mutations in the PTCH1 gene and shows a high level of penetrance and variable expressivity. The syndrome is characterized by developmental abnormalities or neoplasms and is diagnosed with 2 major criteria, or with 1 major and 2 minor criteria. Here, we report a new clinical manifestation associated with this syndrome in a boy affected by NBCCS who had congenital orbital teratoma at birth. Later, at the age of 15 years, he presented with 4 major and 4 minor criteria of NBCCS, including multiple basal cell carcinoma and 2 odontogenic keratocysts of the jaw, both confirmed by histology, more than 5 palmar pits, calcification of the cerebral falx, extensive meningeal calcifications, macrocephaly, hypertelorism, frontal bosses, and kyphoscoliosis. PTCH1 mutation analysis revealed the heterozygous germline mutation c.290dupA. This mutation generated a frameshift within exon 2 and an early premature stop codon (p.Asn97LysfsX43), predicting a truncated protein with complete loss of function. Identification of this mutation is useful for genetic counseling. Although the clinical symptoms are well-known, our case contributes to the understanding of phenotypic variability in NBCCS, highlighting that PTCH1 mutations cannot be used for predicting disease burden and reinforces the need of a multidisciplinary team in the diagnosis, treatment, and follow-up of NBCCS patients.

PAS kinase (PASK) is a nutrient sensor that is highly conserved throughout evolution. PASK-deficient mice reveal a metabolic phenotype similar to that described in S6 kinase-1 S6K1-deficient mice that are protected against obesity. Hypothalamic metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR), play an important role in feeding behavior, the homeostasis of body weight, and energy balance. These sensors respond to changes in nutrient levels in the hypothalamic areas involved in feeding behavior and in neuroblastoma N2A cells, and we have recently reported that those effects are modulated by the anorexigenic peptide glucagon-like peptide-1 (GLP-1). Here, we identified PASK in both N2A cells and rat VMH and LH areas and found that its expression is regulated by glucose and GLP-1. High levels of glucose decreased Pask gene expression. Furthermore, PASK-silenced N2A cells record an impaired response by the AMPK and mTOR/S6K1 pathways to changes in glucose levels. Likewise, GLP-1 effect on the activity of AMPK, S6K1, and other intermediaries of both pathways and the regulatory role at the level of gene expression were also blocked in PASK-silenced cells. The absence of response to low glucose concentrations in PASK-silenced cells correlates with increased ATP content, low expression of mRNA coding for AMPK upstream kinase LKB1, and enhanced activation of S6K1. Our findings indicate that, at least in N2A cells, PASK is a key kinase in GLP-1 actions and exerts a coordinated response with the other metabolic sensors, suggesting that PASK might play an important role in feeding behavior.

The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in different types of cancer. The aim of the present study was to evaluate the clinicopathological significance of ERCC1 expression in breast cancer patients. We analyzed the immunohistochemical expression of ERCC1 in a tissue microarray from 135 primary breast carcinomas and correlated the immunohistochemical findings with clinicopathological factors and outcome data. ERCC1 expression analysis was available for 109 cases. In this group, 58 (53.2%) were positive for ERCC1. ERCC1-positive expression was correlated with smaller tumor size (P=0.007) and with positivity for estrogen receptor (P=0.040), but no correlation was found with other clinicopathological features. Although not statistically significant, triple negative breast cancers were more frequently negative for ERCC1 (61.5% of the cases) compared to the non-triple negative breast cancer cases (41.5%). In conclusion, ERCC1 expression correlated significantly with favorable prognostic factors, such as smaller tumor size and ER-positivity, suggesting a possible role for ERCC1 as a predictive and/or prognostic marker in breast cancer., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Insulin receptor substrate (IRS) proteins play important roles in hepatic nutrient homeostasis. Since glucokinase (GK) and glucokinase regulatory protein (GKRP) function as key glucose sensors, we have investigated the expression of GK and GKRP in liver of Irs-2 deficient mice and Irs2(-/-) mice where Irs2 was reintroduced specifically into pancreatic β-cells [RIP-Irs-2/IRS-2(-/-)]. We observed that liver GK activity was significantly lower (p<0.0001) in IRS-2(-/-) mice. However, in RIP-Irs-2/IRS-2(-/-) mice, GK activity was similar to the values observed in wild-type animals. GK activity in hypothalamus was not altered in IRS-2(-/-) mice. GK and GKRP mRNA levels in liver of IRS-2(-/-) were significantly lower, whereas in RIP-Irs-2/IRS-2(-/-) mice, both GK and GKRP mRNAs levels were comparable to wild-type animals. At the protein level, the liver content of GK was reduced in IRS-2(-/-) mice as compared with controls, although GKRP levels were similar between these experimental models. Both GK and GKRP levels were lower in RIP-Irs-2/IRS-2(-/-) mice. These results suggest that IRS-2 signalling is important for maintaining the activity of liver GK. Moreover, the differences between liver and brain GK may be explained by the fact that expression of hepatic, but not brain, GK is controlled by insulin. GK activity was restored by the β-cell compensation in the RIP-Irs-2/IRS-2 mice. Interestingly, GK and GKRP protein expression remained low in RIP-Irs-2/IRS-2(-/-) mice, perhaps reflecting different mRNA half-lives or alterations in the process of translation and post-translational regulation.

The anorexigenic peptide, glucagon-like peptide-1 (GLP-1), reduces glucose metabolism in the human hypothalamus and brain stem. The brain activity of metabolic sensors such as AMP-activated protein kinase (AMPK) responds to changes in glucose levels. The mammalian target of rapamycin (mTOR) and its downstream target, p70S6 kinase (p70S6K), integrate nutrient and hormonal signals. The hypothalamic mTOR/p70S6K pathway has been implicated in the control of feeding and the regulation of energy balances. Therefore, we investigated the coordinated effects of glucose and GLP-1 on the expression and activity of AMPK and p70S6K in the areas involved in the control of feeding. The effect of GLP-1 on the expression and activities of AMPK and p70S6K was studied in hypothalamic slice explants exposed to low- and high-glucose concentrations by quantitative real-time RT-PCR and by the quantification of active-phosphorylated protein levels by immunoblot. In vivo, the effects of exendin-4 on hypothalamic AMPK and p70S6K activation were analysed in male obese Zucker and lean controls 1 h after exendin-4 injection to rats fasted for 48 h or after re-feeding for 2-4 h. High-glucose levels decreased the expression of Ampk in the lateral hypothalamus and treatment with GLP-1 reversed this effect. GLP-1 treatment inhibited the activities of AMPK and p70S6K when the activation of these protein kinases was maximum in both the ventromedial and lateral hypothalamic areas. Furthermore, in vivo s.c. administration of exendin-4 modulated AMPK and p70S6K activities in those areas, in both fasted and re-fed obese Zucker and lean control rats.

Context: Most tumors in Carney complex (CNC) are benign, including primary pigmented nodular adrenocortical disease (PPNAD), the main endocrine tumor in CNC. Adrenocortical cancer (AC) has never been observed in the syndrome. Herein, we describe a large Azorean family with CNC caused by a point mutation in the PRKAR1A gene coding for type 1-α (RIα) regulatory subunit of the cAMP-dependent protein kinase A, in which the index patient presented with AC., Objective: We studied the genotype-phenotype correlation in CNC., Design and Setting: We reported on case series and in vitro testing of the PRKAR1A mutation in a tertiary care referral center., Patients: Twenty-two members of a family were investigated for Cushing syndrome and other CNC components; their DNA was sequenced for PRKAR1A mutations., Results: Cushing syndrome due to PPNAD occurred in four patients, including the proposita who presented with AC and three who had Cushing syndrome and/or PPNAD. Lentigines were found in six additional patients who did not have PPNAD. A base substitution (c.439A>G/p.S147G) in PRKAR1A was identified in the proposita, in the three others with PPNAD, in the proposita's twin daughters who had lentigines but no evidence of hypercortisolism, and in five other family members, including one without lentigines or evidence of hypercortisolism. Unlike in other RIα defects, loss of heterozygosity was not observed in AC. The S147G mutation was compared to other expressed PRKAR1A mutations; it led to decreased cAMP and catalytic subunit binding by RIα and increased protein kinase A activity in vitro., Conclusions: In a large family with CNC, one amino acid substitution caused a spectrum of adrenal disease that ranged from lack of manifestations to cancer. PPNAD and AC were the only manifestations of CNC in these patients, in addition to lentigines. These data have implications for counseling patients with CNC and are significant in documenting the first case of AC in the context of PPNAD.

Apomixis, an asexual mode of reproduction through seeds, holds much promise for agricultural advances. However, the molecular mechanisms underlying this trait are still poorly understood. We previously isolated several transcripts representing novel sequences differentially expressed in reproductive tissues of sexual and apomictic plants. Here, we report the characterization of two of these unknown RNA transcripts (experimental codes N17 and N22). Since original fragments showed no significant homologies to sequences at databases, preliminary genomic PCR experiments were carried out to discard possible contaminations. RACE extension on flanking regions provided longer sequences for the candidates and additional related transcripts, which revealed similarity to LTR retrotransposons carrying short transduplicated segments of protein-coding genes. Interestingly, some transduplicated segments corresponded to genes previously associated with apomictic development. Gene copy number estimations revealed a moderate representation of the elements in the genome, with significantly increased numbers in a sexual genotype with respect to an apomictic one. Genetic mapping of N17 showed that a copy of this particular element was located onto Paspalum notatum linkage group F3c, at a central non-recombinant region resembling a centromere. Expression analysis showed an increased activity of N17 and N22 sense strands in ovules of the sexual genotypes. A retrotransposon-specific differential display analysis aimed at detecting related sequences allowed the identification of a complex family, with the majority of its members represented in the sexual genotype. Our results suggest that these elements could be participating in regulatory pathways related to apomixis and sexuality.

Background: A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication., Methods: The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer., Results: We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are equally important to stratify different survival outcomes in non-TNBC as in TNBC. We also showed that the NPI retains the ability to stratify and predict survival of TNBC patients., Conclusion: The importance of this study relies on the need of prognostication improvements on TNBC, showing, at a clinical standpoint, that Nottingham Prognostic Index is as a truthful prognostic tool in TNBC.

Surface colonization is an essential step in biofilm development. The ability of oral pathogens to adhere to tooth surfaces is directly linked with the presence of specific molecules at the bacterial surface that can interact with enamel acquired pellicle ligands. In light of this, the aim of this study was to verify inhibitory and antibiofilm action of lectins from the Diocleinaesubtribe against Streptococcus mutans and Streptococcus oralis. The inhibitory action against planctonic cells was assessed using lectins from Canavaliaensi formis (ConA), Canavalia brasiliensis (ConBr), Canavalia maritima (ConM), Canavalia gladiata (CGL) and Canavalia boliviana (ConBol). ConBol, ConBr and ConM showed inhibitory activity on S. mutans growth. All lectins, except ConA, stimulated significantly the growth of S. oralis. To evaluate the effect on biofilm formation, clarified saliva was added to 96-well, flat-bottomed polystyrene plates, followed by the addition of solutions containing 100 or 200 µg/mL of the selected lectins. ConBol, ConM and ConA inhibited the S. mutans biofilms. No effects were found on S. oralis biofilms. Structure/function analysis were carried out using bioinformatics tools. The aperture and deepness of the CRD (Carbohydrate Recognition Domain) permit us to distinguish the two groups of Canavalia lectins in accordance to their actions against S. mutans and S. oralis. The results found provide a basis for encouraging the use of plant lectins as biotechnological tools in ecological control and prevention of caries disease.