Search

The constant passage of trains on the railways tracks causes, in the course of time, deviations that must be corrected periodically by means of a track calibration process. It consists of designing a new layout, called recreated horizontal alignment (RHA), as close as possible to the deformed center track fulfilling also the technical constraints according to the operational requirements of the railway. In recent years, different models have been proposed to address this task. This paper proposes, first, a new geometrical model that works with continuous variables for the definition of horizontal alignments (HAs) to deal with nonsymmetric transition curves at both sides of a circular curve and second, an optimization algorithm to compute the recreated alignment suitable in sinuous railway sections. This new mathematical model frees the optimization process from the need to previously identify the geometric elements (tangents, circular curves, and transition curves) of the HA. The usefulness of this model is tested with two academic examples showing its good behavior and in a real case study, where this algorithm is compared with the solution adopted by the engineers in a section of the railway line Ourense–Monforte in the NW of Spain. [ABSTRACT FROM AUTHOR]

Miami‐Dade County (MDC) has over 112,000 septic systems, some of which are at risk of compromise due to water table rise associated with sea level rise. MDC is surrounded by protected water bodies, including Biscayne Bay, with environmentally sensitive ecosystems and is underlain by highly transmissive karstic limestone. The main objective of the study is to provide first estimates of the locations and magnitudes of septic return flows to discharge endpoints. This is accomplished by leveraging MDC's county‐scale surface‐groundwater model using pathline analysis to estimate the transport and discharge fate of septic system flows under the complex time history of groundwater flow response to pumping, canal management, storms, and other environmental factors. The model covers an area of 4772 km2 in Southeast Florida. Outputs from the model were used to create a 30‐year (2010 to 2040) simulation of the spatial–temporal pathlines from septic input locations to their termination points, allowing us to map flow paths and the spatial distribution of the septic flow discharge endpoints under the simulated conditions. Most septic return flows were discharged to surface water, primarily canals 52,830 m3/d and Biscayne Bay (5696 m3/d), and well fields (14,066 m3/d). Results allow us to identify “hotspots” to guide water quality sampling efforts and to provide recommendations for septic‐to‐sewer conversion areas that should provide most benefit by reducing nutrient loading to water bodies. [ABSTRACT FROM AUTHOR]

Ecological restoration requires a holistic view of the interconnectedness between degraded areas, remaining ecosystems, and the repercussions of land use and other socioeconomic costs. In this study, we analyze how biological priorities for restoration change when ecological, social, and economic feasibility are considered. A multi‐criteria approach was used to prioritize restoration areas, using the Mexican side of the transboundary Grijalva‐Usumacinta basin (78,831 km2) as a study model, one of Mexico's most important regions, thanks to its hydrology, biology, and social conditions. Fourteen indicators of biological value and feasibility for restoration were identified. The results showed that when considering only biological factors (B scenario), 9.35% of the basin area had high or very high priority for restoration within or near natural protected areas (NPAs). When including feasibility (B + F scenario), the area with high to very high priority values for restoration increased to 34.3%. This means that many feasible areas had medium or low biological priority for restoration, and consequently, in many cases, there is a tradeoff between the possible biological recovery versus viability derived mainly from socioeconomic factors. Without discerning where restoration can offer the most pronounced ecological and socioeconomic benefits, efforts risk being misdirected or squandered. This approach provides a suitability assessment useful for decision‐makers and stakeholders because it generates a more complete picture of opportunities and threats to make a final selection of priority areas for intervention. [ABSTRACT FROM AUTHOR]

Fatigue is common in breast‐cancer survivors. Our study assessed fatigue longitudinally in breast cancer patients receiving adjuvant radiotherapy (RT) and aimed to identify risk factors associated with long‐term fatigue and underlying fatigue trajectories. Fatigue was measured in a prospective multicenter cohort (REQUITE) using the Multidimensional Fatigue Inventory (MFI‐20) and analyzed using mixed models. Multivariable logistic models identified factors associated with fatigue dimensions at 2 years post‐RT and latent class growth analysis identified individual fatigue trajectories. A total of 1443, 1302, 1203 and 1098 patients completed the MFI‐20 at baseline, end of RT, after 1 and 2 years. Overall, levels of fatigue significantly increased from baseline to end of RT for all fatigue dimensions (P <.05) and returned to baseline levels after 2 years. A quarter of patients were assigned to latent trajectory high (23.7%) and moderate (24.8%) fatigue classes, while 46.3% and 5.2% to the low and decreasing fatigue classes, respectively. Factors associated with multiple fatigue dimensions at 2 years include age, BMI, global health status, insomnia, pain, dyspnea and depression. Fatigue present at baseline was consistently associated with all five MFI‐20 fatigue dimensions (ORGeneralFatigue = 3.81, P <.001). From latent trajectory analysis, patients with a combination of factors such as pain, insomnia, depression, younger age and endocrine therapy had a particularly high risk of developing early and persistent high fatigue years after treatment. Our results confirmed the multidimensional nature of fatigue and will help clinicians identify breast cancer patients at higher risk of having persistent/late fatigue so that tailored interventions can be delivered. [ABSTRACT FROM AUTHOR]

This document is a reply to comments on a previously published paper about the risk factors for fatigue in breast cancer patients who have undergone radiotherapy. The authors explain that they focused on late fatigue because there is a lack of understanding about this aspect of fatigue in breast cancer patients. They also address concerns about missing data and attrition rates in their study, stating that mortality did not substantially influence the attrition rate. The authors express gratitude for the opportunity to discuss their research and express interest in future collaborations to further understand fatigue in breast cancer patients. [Extracted from the article]

Background: Currently, dementia training is only offered in a few large medical centers in a handful of Latin America ́s biggest cities. Reduced access and the heterogeneous quality of dementia education for clinicians hinder the diagnosis and treatment of neurodegeneration in Latin America. Aim: This project aims to fill the education gaps and increase specialist´s diagnostic and therapeutic skills in neurodegenerative diseases through an interactive online Spanish‐language pilot program tailored for Latin America. Methods: We put together a 108 hour curriculum formed by four modules: basic aspects of behavioral neurology, neurobehavioral and neuropsychiatric syndromes,treatment, and other aspects of neurodegenerative diseases. It was delivered by 35 brain health experts and reviewers that coolaborate with the Global Brain Health Institute in at the University of California, San Francisco to a pilot group formed by 35 geriatricians, neurologists and psychiatrists from six Latin American Countries (Peru, Mexico, Chile, Colombia, Ecuador, and Venezuela). An initial and final evaluations were performed with the Spanish‐dementia knowledge assessment scale (Carnes et al, 2021), the Frontotemporal Dementia Knowledge Scale (Magrath et al 2021) and clinical cases. In addition, short evaluations submitted by professor were answered before and after each class. Separately, we requested feedback from the students about the course. Results: Comparing the overall scores between the initial and final evaluation, there was a 7% increase in the Geriatrician´s score, 4% in Neurologists´ score and 9% in the Psychiatrist's score. The greatest increase was in Frontotemporal Dementia Knowledge. (Figures 1 and 2). The topics with the worse baseline scores were clinical evaluation attention, executive functions, and atypical Alzheimer´s Disease. We observed an increase in knowledge after every class. Most of the feedback brought to light that there were many topics that specialists had not had the opportunity to learn before such as sleep in neurodegeneration, traumatic encephalopathy, and atypical dementia syndromes. Conclusion: It is imperative to find ways of bringing education to regions where dementia prevalence is increasing, and specialist do not have enough knowledge. Online programs are feasible and effective strategies to close educational gaps. [ABSTRACT FROM AUTHOR]

Objective: Sleep apnea and snoring have been associated with type 2 diabetes, with BMI playing a role in the pathway, but the directions of causality are unclear. This study examined the causal associations of sleep apnea and snoring with type 2 diabetes while assessing the role of BMI using multiple genetic methods. Methods: Five genetic methods were used: two‐sample; bidirectional univariable Mendelian randomization (MR) inverse variance‐weighted (MR‐IVW); multivariable MR‐IVW; network MR; and latent causal variable method. Results: Compared with univariable MR‐IVW, the odds ratio (95% CI) of type 2 diabetes for genetically predicted sleep apnea and snoring using the largest genome‐wide association study decreased dramatically, from 1.61 (95% CI: 1.16‐2.23) to 1.08 (95% CI: 0.59‐1.97) and from 1.98 (95% CI: 1.25‐3.13) to 1.09 (95% CI: 0.64‐1.86) after adjustment for BMI. Network MR showed that BMI accounts for 67% and 62% of the total effect of sleep apnea and snoring on type 2 diabetes, respectively. The latent causal variable suggested that sleep apnea and snoring have no direct causal effect on type 2 diabetes. Conclusions: These results first suggest that the associations of sleep apnea and snoring with type 2 diabetes were mainly driven by BMI. The possible indirect effects of sleep apnea and snoring on type 2 diabetes through BMI cannot be ruled out. [ABSTRACT FROM AUTHOR]

Sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) influences on cardiac rhythm at the onset of exercise, a time of rapid autonomic adjustments, are clinically important areas of investigation. Continuous wavelet transform (CWT) involves time‐frequency‐based heart rate variability (HRV) analysis allowing investigation of autonomic influences on cardiac rhythm during short durations of exercise. Therefore, the purpose of this study was to characterize SNS and PNS influences on cardiac rhythm at the onset of isometric exercise in healthy young adults. CWT analysis was retrospectively applied to R‐R interval data (electrocardiogram) previously collected from 14 healthy young adults (26 ± 2 years) who performed 30‐s, one‐legged, isometric, calf exercise at 70% maximal voluntary contraction (MVC; 70% MVC trial) or rested (0% MVC trial). Absolute and normalized low‐frequency (aLF, nLF; 0.04–0.15 Hz) and high‐frequency (aHF, nHF; 0.15–0.4 Hz) bands and LF/HF were used to analyze one 30‐s baseline period and six 5‐s time windows during the 30‐s exercise (70% MVC) or rest (0% MVC). Statistical analysis involved two‐way analysis of variance with post‐hoc analysis. aHF, aLF, LF/HF, nHF, and nLF displayed a trial‐time interaction (all p ≤ 0.027). In the 70% compared to the 0% MVC trial, aHF and nHF were lower after 5–30 s (all p ≤ 0.040), aLF was lower after 20–30 s (all p ≤ 0.011) and LF/HF and nLF were higher after 5–20 s (all p ≤ 0.045). These results indicate the reduction of the PNS influence on cardiac rhythm begins sooner than the augmentation of the SNS influence at the onset of isometric exercise in healthy young adults. [ABSTRACT FROM AUTHOR]

The Southern Patagonian Andes at the latitude of the Chile Triple junction in Argentina and Chile (46°–47.5°S) are the object of an ongoing discussion regarding their orogenic evolution in terms of tectonic crustal thickening and exhumation. Recent works point to an Early Cretaceous onset of shortening according to observations in foreland sequences. The ensuing Cenozoic thermal history of the region was influenced by increased shortening, oceanic‐ridge collision and formation of asthenospheric windows in a dynamic subduction setting. Furthermore, the onset of Patagonian glaciations after 7 Ma added increased complexities to the analysis of the main drivers of crustal cooling in this region. We applied zircon (U‐Th)/He and apatite fission track thermochronometry, and inverse thermal modeling to unravel the thermal history throughout different structural domains of the Patagonian Andes. New thermochronological data and thermal models showed a previously unrecognized set of Cretaceous cooling ages (120‐80 Ma) toward the foreland, that we relate to the onset of contraction during initial tectonic inversion. Toward the hinterland, Cenozoic cooling ages predominate, and are related to Oligocene‐Miocene contraction in response to increased subduction velocities. Based on the regional distribution of thermochronological ages and on results from thermal modeling, a resetting of the zircon (U‐Th)/He and apatite fission track systems in response to crustal heating related to the formation of an asthenospheric window after 16 Ma appears unlikely. After 7 Ma cooling rates increased in response to enhanced glacial erosion. Plain Language Summary: In this work, we have used thermochronometers, basically clocks that start recording time once a rock‐sample has crossed a given temperature in the crust, to track the cooling of rock‐samples from the Patagonian Andes between 46.5°S and 48°S. In this area, several processes influenced the evolution of the landscape such as mountain building, glaciers erosion, and deep‐seated processes within the mantle. All of them may have left a trace in thermochronometers. Our goal is to determine the role of mountain building processes in rock cooling in this area. Our results suggest that rocks cooled in response to mountain building during the Cretaceous in what could be considered the first phase of construction of the Andes in the area. Mountain building processes continued influencing rock cooling during the Miocene, nearly 100 million‐years after the first phase. During the last 7 million‐years before the present, the onset of glacial erosion enhanced rock cooling. Finally, we found no records that the rocks heated in response to deep‐seated mantle processes. Key Points: We applied low‐temperature thermochronology and thermal modeling to study timing and drivers of cooling in the Patagonian Andes at the Chile triple junctionA Cretaceous cooling phase between 120 and 80 Ma was detected, directly linked to the first recorded Andean orogenic phase of the Patagonian AndesA 30‐10 Ma cooling phase is related to the main phase of crustal shortening during increased convergence prior to the collision of the Chile ridge; 7‐0 Ma cooling is likely linked to glaciations rather than to the development of slab window [ABSTRACT FROM AUTHOR]

Range expansion in plant populations, especially at the colonization front, can be either limited by disproportionately large effects of antagonistic interactions or facilitated by their release. How the strength of antagonistic interactions changes along successional gradients during range expansion is still poorly documented, especially when diverse assemblages of plant antagonists (rodents, invertebrates and birds) combine within interaction networks.We study the changes in individual‐based, predispersal seed–pulp predator networks along a colonization gradient in a rapidly expanding Juniperus phoenicea population in Doñana National Park (SW Spain). Additionally, we analysed the role of individual plant traits and neighbourhood attributes in network configuration by using Exponential Random Graph Models.Seven seed–pulp consumer animal species varied significantly in their frequency of interaction and prevalence. While invertebrate species were well‐established in old and intermediately mature stands, greenfinch Chloris chloris was dominant at the colonization front. Variable species roles and spread of interactions among individual plants generated changes in the configuration of interactions during plant expansion.Individual plant traits strongly determined the topology of these networks, although with differences between stands. Increasing individual crop size and seeds per cone increased the interaction odds of individual plants, while seed viability showed the opposite effect. The network topology at the colonization front appeared less driven by individual traits, possibly because of the short interaction history of this recently established area. The disproportionately large effect of C. chloris in these recently established stands, potentially resulted in large seed losses during range expansion.Synthesis. Turnover of antagonistic interactions, characterized the colonization front, resulting in more heterogeneous interaction strengths among individual plants. We found no evidence for a complete or sizeable antagonistic release of J. phoenicea at the colonization front promoting this rapid expansion. It becomes necessary to explore interactions with seed dispersers to understand how antagonistic and mutualistic plant–animal interactions balance during range expansion. Our study highlights the importance of an individual‐based approach in understanding how interactions are structured and driven in natural changing landscapes. [ABSTRACT FROM AUTHOR]

This work deals with the design of horizontal alignments (HAs) for its application in intelligent civil systems. Two consecutive tasks are performed: the random generation of admissible horizontal alignments (AHAs; alignments verifying some geometric constraints set in advance) and the optimal design of layouts joining two given points. A rigorous mathematical analysis of the first task leads to a novel algorithm for random generation of alignments, which is used to develop the global optimization method proposed for the second task. The usefulness of this approach is shown on some practical applications. First, two problems with applications in robotics, pipe layout design, and forest road design are solved in realistic situations. Next, the random generation of AHAs in mountainous terrain is addressed. Finally, the model is extended to 3D alignments and a real case study is presented, designing a bypass on the N‐640 Spanish national road, surrounding the urban area of Monterroso. [ABSTRACT FROM AUTHOR]

Introduction: M Scan-Fit, an automated method for motor unit number estimation (MUNE), was assessed in muscles innervated by the facial nerve.Methods: Healthy volunteers were recruited. M Scans were recorded twice from nasalis and depressor anguli oris (DAO) muscles, and then fitted to a probabilistic model.Results: Twenty-one subjects were evaluated; 38% were females and 62% were males, with a mean age of 34.71 years. The average number of MUs was 38.57 on both testing occasions (t ≤ 0.0001; P = 1.0) for the nasalis. For the DAO, results were 20.62 MUs for the first and 23.48 for the second (t = -2.12; P = .04). Pearson's interrater correlation coefficients were 0.96 (P < .0001) for nasalis and 0.87 (P ≤ .01) for DAO. Intraclass correlation coefficients were 0.88 (P ≤ .01) for nasalis and 0.39 (P = .37) for DAO.Discussion: M Scan-Fit MUNE is an automated, accurate, reliable method of estimating MU number and size from facial muscles. [ABSTRACT FROM AUTHOR]

Summary: The issue of standardization in synthetic biology is a recurring one. As a discipline that incorporates engineering principles into biological designs, synthetic biology needs effective ways to communicate results and allow different researchers (both academic and industrial) to build upon previous results and improve on existing designs. An aspect that is left out of the discussions, especially when they happen at the level of academic and industrial consortia or policymaking, is whether or not standards are applicable or even useful in everyday research practice. In this caucus article, we examine this particular issue with the hope of including it in the standardization discussions agenda and provide insights into a topic that synthetic biology researchers experience daily. [ABSTRACT FROM AUTHOR]

Summary: Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) are a leading cause of drug‐induced liver injury (DILI) across the world. Ibuprofen is one of the most commonly used and safest NSAIDs, nevertheless reports on ibuprofen‐induced hepatotoxicity are available. Aim: To analyse previously published information on ibuprofen‐induced liver injury for a better characterisation of its phenotypic expression. Method: A systematic search was performed and information on ibuprofen‐induced liver injury included in case series and case reports, in terms of demographic, clinical, biochemical and outcome data, was analysed. Results: Twenty‐two idiosyncratic ibuprofen hepatotoxicity cases were identified in the literature, suggesting a very low prevalence of this type of DILI. These patients had a mean age of 31 years and 55% were females. Mean cumulative dose of ibuprofen and time to onset were 30 g and 12 days, respectively. Hepatocellular injury was the most frequently involved liver injury pattern. Six cases developed vanishing bile duct syndrome. Full recovery occurred in 11 patients after a mean time of 14 weeks, whereas five cases evolved to acute liver failure leading to death/liver transplantation. Conclusions: When assessing potential hepatotoxicity cases, physicians should keep in mind that ibuprofen has been associated with hepatotoxicity in the literature. Ibuprofen‐associated DILI presents commonly as hepatocellular damage after a short latency period. Published reports on ibuprofen hepatotoxicity leading to liver failure resulting in liver transplantation or death are available. However, due to the apparent low absolute risk of ibuprofen‐induced liver complications, ibuprofen can be regarded as an efficacious and safe NSAID. [ABSTRACT FROM AUTHOR]

The nature and the strength of plant–frugivore interactions often vary along an antagonism–mutualism continuum and are highly influenced by the local ecological context (e.g. level of environmental disturbances). However, little is known concerning how the local ecological setting where plant–frugivore interactions take place affects the seed dispersal effectiveness (SDE) and, eventually, plant recruitment. This knowledge gap relates to the scarcity of empirical investigations on individual‐based plant–frugivore networks. We assessed whether the assembly of interaction modes (antagonist and mutualist) of the dwarf palm Chamaerops humilis (Arecaeae) affect the individual and the population level SDE in two Mediterranean sites differing in perturbation levels. We analysed the frequency distribution of interaction typologies and test its relationship with variation among individual palms in SDE. Additionally, we document how variation in interaction motif frequency (e.g. overrepresented interaction typologies) relates to changes in the SDE landscape of both disturbed study sites. We found that the interaction typologies of individual palms and its frugivores did not occur randomly. In a more complex landscape, interactions were more diverse and less dominated by simpler typologies, which may increase the stability of the plant–disperser interaction over the long term. We demonstrate that plants that interact with a more complex assemblage of frugivores, including both mutualistic and antagonistic partners, had the highest probability of recruitment. We found that the highly variable SDE among individual palms resulted from a few interaction modes occurring at higher than expected frequencies. We suggest this may be a reasonably frequent situation in diversified frugivore assemblages with a high heterogeneity of functional effects among mutualistic and antagonistic partners. [ABSTRACT FROM AUTHOR]

Background and objective: Although corn is the most consumed and studied cereal in Mexico as food, its potential in fermented beverage production is less considered. The objective was to study the morphological and physiochemical changes during malting for Palomero and Puma corns, and to compare them with malted barley to determine the potentials of this cereal in the beer industry. Findings: The SEM images of the malted starches showed a selective enzymatic attack and germination rate and reducing sugars behaved as S‐shape (logistic curve). The X‐ray diffraction patterns showed that the process did not modify the crystalline structure of these starches. The pasting profile showed changes in the peak viscosity and final viscosity, associated with amylose degradation, debranching of amylopectin, and the increase in reducing sugars. The IR analysis showed that during the malting time, the lipids had a drastic change. Conclusions: Significant changes were found in the nutrimental composition after malting such as loss in fat and carbohydrates, while no significant differences were found in protein and ashes. The SEM images of the malting showed a selective enzymatic attack, and X‐ray diffraction patterns showed that process does not modify the crystalline structure of this starch. Changes in the pasting profile indicate that the malting decreases the peak and final viscosity. Significance and novelty: The X‐ray results clearly showed that the enzymatic attack takes place on the amorphous component of the starch, while in the case of corn the crystalline A‐type orthorhombic structure does not suffer any change. These results indicate that corn malt can be suitable for brewing purposes. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) has a complex genetic aetiology, where the precise mechanisms underlying the selective vulnerability of brain regions remain unknown. Method: We leveraged summary‐based data from genome‐wide association studies (GWASs) and performed LD‐score regression to estimate pairwise genetic correlations between FTD risk and cortical brain imaging. Then, we isolate specific genomic loci with a shared aetiology between FTD and brain structure. We also performed functional annotation, summary‐based‐data Mendelian randomisation for eQTL using human peripheral blood and brain tissue data and evaluated the gene expression in mice targeted brain regions to better understand the dynamics of the FTD candidate genes. Result: Pairwise genetic correlation estimates between FTD and brain morphology measures were high but not statistically significant. We identified five brain regions with a strong genetic correlation (rg > 0.45) with FTD risk. Functional annotation identified eight protein‐coding genes. Building upon these findings, we show in a mouse model of FTD that cortical NSF expression decreases with age. Conclusion: Our results highlight the molecular and genetic overlap between brain morphology and higher risk for FTD, specifically for the right inferior parietal surface area and right medial orbitofrontal cortical thickness. In addition, our findings implicate NSF gene expression in the aetiology of FTD. [ABSTRACT FROM AUTHOR]

Background: Self‐administered online cognitive testing offers a cost‐effective and flexible alternative to in‐person neuropsychological assessments. We used the Creyos platform (previously named Cambridge Brain Sciences) to assess cognitive function in a large sample (N = 1673) of middle aged and older adults participating in the PISA (Prospective Imaging Study of Aging) study. PISA aims to characterise the early symptoms and progression of Alzheimer's disease at its prodromal phase. Method: We have utilised our Australia‐wide population based sample recruitment pool of research participants with genome wide genotyping. Participants completed a comprehensive online survey and online cognitive assessments, including Creyos, consisting of 12 self‐administered tasks covering memory, executive function, language, and visuo‐spatial domains. Using genetic profile scores in a sample size of 1,673 (70% female, aged 42‐75 years, mean 60.8). We tested the association between cognitive test results and genetic risk for Alzheimer's disease and related phenotypes including structural neuroimaging measures. Results: Our findings indicate a significant association of Alzheimer's polygenic risk scores (PRS) with cognitive test results in healthy individuals within memory and executive function domains. The results of analyses with additional genetic profile scores including psychiatric traits and structural neuroimaging measures will also be presented. Conclusion: Those who are at high genetic risk for Alzheimer's disease have reduced cognitive function prior to dementia diagnosis from middle age. Our results highlight the utility of online cognitive testing as a cost‐effective alternative to in person testing for large scale studies and the potential for it's used as a pre‐screening approach to identify those at high risk of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Ibuprofen is a worldwide used non‐steroidal anti‐inflammatory drug which may cause acute liver injury (ALI) requiring liver transplantation. We aimed to unveil the molecular pathways involved in triggering ibuprofen‐induced ALI, which, at present, remain elusive. First, we investigated activation of essential pathways in human liver sections of ibuprofen‐induced ALI. Next, we assessed the cytotoxicity of ibuprofen in vitro and developed a novel murine model of ibuprofen intoxication. To assess the role of JNK, we used animals carrying constitutive deletion of c‐Jun N‐terminal kinase 1 (Jnk1−/−) or Jnk2 (Jnk2−/−) expression and included investigations using animals with hepatocyte‐specific Jnk deletion either genetically (Jnk1Δhepa) or by siRNA (siJnk2Δhepa). We found in human and murine samples of ibuprofen‐induced acute liver failure that JNK phosphorylation was increased in the cytoplasm of hepatocytes and other non‐liver parenchymal cells (non‐LPCs) compared with healthy tissue. In mice, ibuprofen intoxication resulted in a significantly stronger degree of liver injury compared with vehicle‐treated controls as evidenced by serum transaminases, and hepatic histopathology. Next, we investigated molecular pathways. PKCα, AKT, JNK and RIPK1 were significantly increased 8 h after ibuprofen intoxication. Constitutive Jnk1−/− and Jnk2−/− deficient mice exhibited increased liver dysfunction compared to wild‐type (WT) animals. Furthermore, siJnk2Δhepa animals showed a dramatic increase in biochemical markers of liver function, which correlated with significantly higher serum liver enzymes and worsened liver histology, and MAPK activation compared to Jnk1Δhepa or WT animals. In our study, cytoplasmic JNK activation in hepatocytes and other non‐LPCs is a hallmark of human and murine ibuprofen‐induced ALI. Functional in vivo analysis demonstrated a protective role of hepatocyte‐specific Jnk2 during ibuprofen ALI. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Modulation of physical exercise (PE) represents an intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie beneficial effects of PE involves the apparent stimulation of adult hippocampal neurogenesis (AHNG). BCI‐838 is a pro‐drug whose metabolite BCI‐632 is one of the most active proneurogenic agents known and is an antagonist at group II metabotropic receptors (mGluR2/3). The drug stimulates AHNG while enhancing learning behavior and exerting anxiolytic and antidepressant properties. We previously demonstrated that the administration of BCI‐838 to a mouse model of cerebral and cerebrovascular accumulation of oligomeric AbE22Q (APPE693Q = "Dutch") reduced learning behavior impairment and anxiety, both of which are associated with the phenotype of Thy1.1‐Dutch APP mice (Kim et al., Mol Psych 2014). Herein, we sought to determine whether BCI‐838 might substitute for PE, and/or whether treatment with a BCI‐838+PE combination might demonstrate synergistic effects in a mouse model of amyloidosis (APPKM670/671NL/PSEN1Δexon9 = APP/PS1). Method: 3‐month‐old APP/PS1 mice were treated with either BCI‐838, PE (running wheels), or a combination of BCI‐838+PE for 1 month. We performed learning behavior tests (novel object recognition and Barnes maze), biochemical, and transcriptomic analyses on the hippocampal dentate gyrus (DG) of APP/PS1 mice. We performed gene set enrichment analysis, drug repurposing, and chemogenomic enrichment analyses to reveal molecular pathways of interest and investigated compounds with transcriptomically similar profiles as well as drug targets and side effects. Result: We report that: (i) BCI‐838, PE, or BCI‐838+PE combination enhanced AHNG, (ii) BCI‐838 alone or associated with PE led to improvement in both spatial and recognition learning behaviors, (iii) BCI‐838 treatment increased mRNA levels of BDNF, metabotropic glutamate receptors, and PIK3C2A of the PI3K‐MTOR pathway, and decreased EIF5A of ketamine‐modulating mTOR activity in the hippocampal DG. qPCR results validated the statistical significance of the association between BCI‐838 treatment and increased levels of BDNF. Conclusion: Our study points to BCI‐838 as a safe and orally active compound capable of mimicking the beneficial effect of exercise on AHNG, learning behavior, and anxiety in the APP/PS1 mouse model. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the spatiotemporal dynamics of human‐wildlife interfaces is important for the sustainable management of protected areas and wildlife conservation. We investigated the drivers of domestic and wild herbivore habitat selection at the edge of an unfenced protected area adjacent to Hwange National Park, Zimbabwe. We used GPS data to quantify the movement patterns of elephant bulls, buffalo and cattle at multiple scales and according to seasonal changes of surface water availability. Cattle, elephant and buffalo prefer open grassland habitats found close to water but elephant and buffalo avoid cattle differently. During the rainy season, cattle enter the protected area daily; buffalo avoid cattle completely at the home range scale, whereas elephant bulls avoid cattle at finer scales by favoring temporal niche shift. Elephant bulls avoid direct encounters with cattle (or people) during the day but come closer to the boundary and to water at night when cattle are kept in enclosures close to the homesteads. During the dry season, when cattle range further into the protected area in search of forage, buffalo and cattle spatial overlap increases as water dependence takes precedence over avoidance. Elephant bulls range closer to the boundary at night and increase the number of excursions into the Communal Area. Cattle herding creates a buffer zone between wildlife areas and human settlements because wild herbivores strongly avoid livestock and people. However, avoidance only lasts as long as resources are abundant. Our study suggests that long‐term planning of both artificial water provisioning and traditional cattle herding practices could help maintaining spatial segregation and thus mitigate conservation conflicts such as pathogen transmission, crop raiding or livestock depredation. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi‐substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes. Design: Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors). Setting: Two large population‐based twin samples from the United States and Australia. Participants: A total of 622 young Australian adults [66% female; μage = 25.9, standard deviation SD) = 3.6] and 474 middle‐aged US males (μage = 56.1SD = 2.6) of predominately Anglo‐Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded. Measurements: Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life‐time multi‐substance use, maximum cannabis use in the young adults and regular cannabis use in the middle‐aged males. Findings: After correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle‐aged males. Conclusions: In exploratory analyses based on young adult and middle‐aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume. [ABSTRACT FROM AUTHOR]

Abstract: In this article, the optimal design of a road joining two terminals is investigated. A geometric model is proposed including horizontal transition curves and vertical curves, obtaining parameterizations for the central axis of the road as well as for its entire surface. These parameterizations allow to express and compute, with great simplicity, the major infrastructure costs, including land acquisition, clearance, pavement, maintenance, and earthwork, where multiple layers of materials with different costs can be handled. The road design problem is formulated as a smooth constrained optimization problem and a two‐stage algorithm is suggested for its numerical resolution. Finally, numerical results are presented in an academic test and in a case study that propose designing a bypass in a Spanish national road (N‐640) to avoid crossing Monterroso's town center. [ABSTRACT FROM AUTHOR]

ABSTRACT: A statistical analysis of 100‐year historic Southern Annular Mode (SAM) time series is carried out, for a set of indices calculated by different methods, in view to understanding their value as simple indicators of climate variability and of the physical processes involved, particularly for the early part of the 20th century. Historic SAM time series available in the literature are analysed together with ones calculated using the 20th‐century reanalysis. A preliminary analysis and comparison is carried out using standard time and space correlations. Distinct differences are observed in the linear relations between the SAM index time series before and after 1950s. A detailed study is carried out using wavelet transform (WT) analysis, in order to better determine the spectral nature and non‐stationarity of the timeseries. The WT spectra reveal an aperiodic, non‐stationary evolution in all cases, with differences in the spectral signature of the various SAM indices during the 20th century. Preferred oscillation periods mainly appear between 2 and 20 years. Important differences between the SAM indices arise from different behaviour on the interannual time scale even in more recent years, as well as non‐stationarity and phase differences on longer time scales. A wavelet coherency (WTC) analysis between the 20th‐century‐reanalysis‐derived SAM time series shows that differences may also arise for indices calculated from the same data source, particularly during the earlier part of the sample. WTC differences appear at times of perturbed El Niño‐Southern Oscillation (ENSO) events. Results using linear as well as a mutual information analysis suggest links between SAM, ENSO, and Pacific‐South American patterns of variability, which may depend on the SAM time series definition. Such behaviour could be due to a combination of factors including the geographic coverage of the SAM calculation methods and data quality, as well as ENSO‐SAM relationships. [ABSTRACT FROM AUTHOR]

Functional electrical stimulation cycling has been proposed as an assistive technology with numerous health and fitness benefits for people with spinal cord injury, such as improvement in cardiovascular function, increase in muscular mass, and reduction of bone mass loss. However, some limitations, for example, lack of optimal control strategies that would delay fatigue, may still prevent this technology from achieving its full potential. In this work, we performed experiments on a person with complete spinal cord injury using a stationary tadpole trike when both cadence tracking and disturbance rejection were evaluated. In addition, two sets of experiments were conducted 6 months apart and considering activation of different muscles. The results showed that reference tracking is achieved above the cadence of 25 rpm with mean absolute errors between 1.9 and 10% when only quadriceps are activated. The disturbance test revealed that interferences may drop the cadence but do not interrupt a continuous movement if the cadence does not drop below 25 rpm, again when only quadriceps are activated. When other muscle groups were added, strong spasticity caused larger errors on reference tracking, but not when a disturbance was applied. In addition, spasticity caused the last experiments to result in less smooth cycling. [ABSTRACT FROM AUTHOR]

Abstract: The conversion of ptaquiloside (PtQ), a bracken fern (Pteridium aquilinum) carcinogen, to pterosin B (PtB), which is involved in the underlying mechanisms of PtQ genotoxicity and carcinogenicity, has been theoretically studied in aqueous neutral (AN) and acid (AA) media, using DFT methods at the PCM(water)‐B3LYP/6‐31G(d)//B3LYP/6‐31G(d) computational level. The β‐elimination of glucose in AN and four reactive channels (A‐D) defined by as many protonation sites in PtQ were calculated. Activation enthalpy decreases (from 42.0 to 12.6 kcal mol−1) in AA relative to AN suggesting protic catalysis. The most favoured channel A started with protonation of the tertiary O15 hydroxyl of PtQ and SN1 water release with strong stabilisation by the spirocyclopropane ring. Natural population analysis and electron localisation function analysis showed significant electron depopulation of vicinal C−C bonds and the remarkable leaving character of the quaternary carbon, which enhanced the nucleophilic attack of water on the distal methylenes while the glucose fragment was retained. This intermediate was unstable, degrading rapidly to a stable PtB‐glucose‐water‐H+ molecular complex whose calculated electronic spectrum (λmax=271.5 nm) matched the value of an intermediate reported earlier with a different structure. PtQ‐dienone, long assumed as the carcinogenic form of PtQ, is not formed in AA but only and unfavourably so in protonated form assisted by one molecule of water. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs), particles having one or more dimensions below 100 nm, are currently being synthesized through chemical and physical methods on an industrial scale. However, these methods for the synthesis of NPs do not fit with sustainable development goals. NP synthesis, through chemical and physical methods, requires high temperatures and/or pressures resulting in high energy consumption and the generation of large amounts of waste. In recent years, research into the synthesis of NPs has shifted to more green and biological methods, often using microorganisms. A biological approach has many advantages over chemical and physical methods. Reactions are catalysed in aqueous solutions at standard temperature and pressure (cost effective and low energy syntheses). This method does not require solvents or harmful chemicals, making NP biosynthesis a greener and more eco-friendly method. Furthermore, NP synthesis by microbes does not require the use of pure starting materials; thus it can simultaneously be used for the bioremediation of contaminated water, land and waste, and the biosynthesis of NPs. Therefore the biosynthesis of NPs contributes to the sustainable development goals, while the alternative physical and chemical methods exclusively utilize scarce and expensive resources for NP synthesis. [ABSTRACT FROM AUTHOR]

The domestic and wild carnivore interface is complex, yet understudied. Interactions between carnivore species have important implications for direct interference competition, cross-species transmission of shared pathogens and conservation threats to wild carnivores. However, carnivore intraguild interactions are hard to quantify. In this study, we asked 512 villagers residing around a conservation area in the Serengeti Ecosystem, Tanzania, to report on the presence of wild carnivores in their village, the number of domestic dogs Canis familiaris and cats Felis catus in their household and interactions between domestic and wild carnivores. Wild carnivores are abundant near households surrounding the Serengeti National Park, villagers have many free-ranging domestic dogs (and would like to have more) and direct and indirect contacts between wild and domestic carnivores are common. Large carnivores, such as spotted hyenas and leopards, often killed or wounded domestic dogs. Small carnivores, such as mongoose, bat-eared fox, serval and wildcat, are locally abundant and frequently interact with domestic dogs. We demonstrate that interspecific carnivore behavior, human culture and local and regional geography play a complex role in domestic and wild carnivore interaction risk around conservation areas. Through the use of household surveys, we were able to efficiently obtain data on a wide scope of carnivore interactions over a large area, which may provide a direction for future targeted and in-depth research to reduce interspecific conflict. Improving the health and husbandry of domestic animals and reducing the unintentional feeding of wild carnivores could reduce dog-wildlife interactions and the potential for pathogen transmission at the domestic-wild animal interface. [ABSTRACT FROM AUTHOR]

Background: A lower virulence of HIV-1 subtype C (HIV-1C) is suggested to be related to the global dominance of HIV-1C. In this observational study, combining in vivo (clinical monitoring) and in vitro (genotypic, biochemical, and phenotypic assays), we explored whether HIV-1C from East Africa (HIV-1CEA) is more pathogenic due to the evolution of a PYxE-insertion (CPYxEi) in the gag-p6 that also could affect the therapy response. Methods: HIV-1B (n = 112) and HIV-1CEA (n = 128)-infected individuals residing in Sweden were analyzed with regard to Gag-p6 genotype and clinically monitored. Based on the Gag-p6 characteristics, three HIV-1CEA and one HIV-1 B patient-derived p2-INT-recombinant virus (gag-p2/NCp7/p1/p6/pol-PR/RT/IN) were constructed to analyze viral growth kinetics (VGKs) and drug sensitivity assays. Reverse transcriptase (RT) from the same samples was cloned into the heterodimer expression plasmid (pRT6H-PROT) to analyze catalytic efficiency of RT. Results: A higher viral failure rate and lower pre-therapy CD4+ T-cell counts were observed in HIV-1CEA-infected patients compared to HIV-1B-infected patients. In Gag-p6, PTAP-duplication was more common in HIV-1C. HIV-1CEA-infected patients with signature CPYxEi, evidenced very low pre-therapy CD4+ T-cell counts and suboptimal gain in CD4+ T-cells following therapy, as compared to the non-CPYxEi-strains indicating higher virulence. VGKs showed a statistically significant higher replication capacity (RC) for the CPYxEi viruses than the other two non-CPYxEi strains. No statistically significant difference was observed in the catalytic efficiency among HIV-1C RTs. Conclusions: This is the first evidence of polymerase independent increased virulence and RC in HIV-1CEA following PYxE-insertion that is associated with suboptimal CD4+ T-cell gain following therapy initiation. J. Med. Virol. 89:106-111, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Age-related declines in survival and function (senescence) were thought not to exist in wild populations, as organisms, and particularly in invertebrates, do not live long enough. While recent evidence has demonstrated that senescence is both common and measurable even in wild populations under field conditions, there are still organisms that are thought to exhibit 'negligible senescence'. We explore variation in rates and patterns of senescence in the biogerontological model organism, the freshwater pearl mussel Margaritifera margaritifera, across five populations, which differ in their age profile. In particular, we tested the theory of negligible senescence using time-at-death records for 1091 specimens of M. margaritifera. There is clear evidence of senescence in all populations, as indicated by an increase in mortality with age, but the nature of the relationship varies subtly between populations. We find strong evidence of a mortality plateau at later ages in some populations, but this is unequivocally absent from others. We then demonstrate that the temporal scaling of the rates of senescence between five populations of M. margaritifera can be explained by the variation in the thermal environment of the population. Hence, climate change may pose a threat to the demography of this long-lived, endangered species, and a greater understanding of the relationship between river temperature and population structure will be essential to secure the species against global temperature increases. Our findings demonstrate that useful insights can be drawn from a non-invasive monitoring method to derive demographic data, and we suggest a wide-scale application of this method to monitor populations across the whole latitudinal (and, hence, thermal) range of the species. [ABSTRACT FROM AUTHOR]

Throughout Europe, increased levels of land abandonment lead to (re)colonization of old lands by forests and shrublands. Very little is known about the spatial pattern of plants recolonizing such old fields. We mapped in two 21-22-ha plots, located in the Doñana National Park (Spain), all adult individuals of the endozoochorous dwarf palm Chamaerops humilis L. and determined their sex and sizes. We used techniques of spatial point pattern analysis (SPPA) to precisely quantify the spatial structure of these C. humilis populations. The objective was to identify potential processes generating the patterns and their likely consequences on palm reproductive success. We used (1) Thomas point process models to describe the clustering of the populations, (2) random labeling to test the sexual spatial segregation, and (3) mark correlation functions to assess spatial structure in plant sizes. Plants in both plots showed two critical scales of clustering, with small clusters of a radius of 2.8-4 m nested within large clusters with 38-44 m radius. Additional to the clustered individuals, 11% and 27% of all C. humilis individuals belonged to a random pattern that was independently superimposed to the clustered pattern. The complex spatial pattern of C. humilis could be explained by the effect of different seed-dispersers and predators' behavior and their relative abundances. Plant sexes had no spatial segregation. Plant sizes showed a spatial aggregation inside the clusters, with a decreasing correlation with distance. Clustering of C. humilis is strongly reliant on its seed dispersers and stressful environmental conditions. However, it seems that the spatial patterns and dispersal strategies of the dwarf palm make it a successful plant for new habitat colonization. Our results provide new information on the colonization ability of C. humilis and can help to develop management strategies to recover plant populations. [ABSTRACT FROM AUTHOR]

Colleters are secretory structure present on many families including Rubiaceae. Particular characteristics have been described about colleters secretory cells, however senescence process are still under debate. Tocoyena bullata (Vell.) Mart. (Rubiaceae) shoot apex were collected at Jardim Botânico do Rio de Janeiro, RJ/Brazil. Stipules were separated and fragments were fixed in 2.5% glutaraldehyde and 4.0% formaldehyde in 0.05 m sodium cacodylate buffer, pH 7.2, post fixed in 1.0% osmium tetroxide in the same buffer, dehydrated in acetone, critical-point-drying, sputtered coated and observed. For light microscopy fragments were fixed and dehydrated, infiltrated with historesin and stained with 1% toluidine blue. For transmission electron microscopy, the samples were infiltrated with Epoxi resin. Colleters are present on stipule adaxial surface. On the beginning of development, these structures are recognized as small projections. Later on, colleters differentiated and secrete by cuticle rupture. The colleters senescence occurs in a concomitant and indissoluble way of programmed cell death. Ultrastructural analyses during the process strongly suggest the senescence is based on a non-autolitic programmed cell death. T. bullata colleters, present at stipule abaxial surface are cylindrical secretory structures. Colleters secretory cells originated as stipule projections; differentiate; secrete and senesce by programmed cell death. The secretion and the cell dead occurs in a concomitantly and indissoluble way. [ABSTRACT FROM AUTHOR]

Two distantly located promoter regions regulate the dynamic expression of RUNX genes during development: distal P1 and proximal P2 promoters. We have recently described that β-catenin increases total Runx1 mRNA levels in human CD34+ hematopoietic progenitors and enhances spatial proximity with its translocation partner ETO. Here, we report that induction of Wnt/β-catenin signaling in HL60 and Jurkat leukemia-derived cell lines and CD34+ progenitors selectively activate the production of the longer distal P1-Runx1 mRNA isoform. Gain- and loss-of-function experiments revealed that the differential increase in P1-Runx1 expression is accomplished through a minimal β-catenin responsive region that includes a highly conserved TCF/LEF-binding element, located −20/−16 bp upstream of the canonical distal P1-Runx1 transcription start site. We conclude that the distal P1-Runx1 promoter is a direct transcriptional target of Wnt/β-catenin signaling that may be important in normal hematopoiesis or its transition into malignant stem cells during the onset or progression of leukemia. J. Cell. Physiol. 231: 1460-1467, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT There is growing evidence of significant changes in components of the Antarctic climate system, an important issue given the influence Antarctica has on global climate. It is important to infer to what extent these regional changes could be attributed to human-induced processes and to what extent to natural variability. Standard methods such as linear trend estimates or piecewise linear trends can be inadequate because they may result in erratic, non-systematic results, particularly if different scales of variability are present in each record and various records are to be compared. The Orcadas Antarctic Station (Argentina), with daily surface meteorological observations since April 1903, provides Antarctica's longest observational record. This study analyses the Orcadas seasonal surface temperature variability. Multidecadal variability and short-term trends are studied to provide an improved assessment of climate evolution and necessary information for the determination of mechanisms driving regional/local change. A combined method using wavelet transform ( WT), non-linear statistical model approaches and derivative of fits is developed. This methodology is also applied for validation and comparison to the Gomez ice core oxygen isotope record for the 1857-2006 and 1903-2006 time intervals. Significant quasi 50-year and quasi 20-year variability bands were obtained, both for the quarterly and seasonal Orcadas temperature records, with warming (cooling) periods detected between 1903-1912, 1927-1961 and 1972-2004 (1912-1927 and 1962-1972). If seasons are considered, the only one with a fairly sustained warming is summer, where actual cooling is observed only at the beginning, prior to the early 1930s. Quasi 50-year variability was also detected in the Gomez record. Long periods are obtained in the model fits, longer than the time series, which varied with window length. Although not representing variability cycles, they could represent the best fit of the non-linear, non oscillating asymptotic stationary component of the series, i.e. a non-linear trend. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. Method A total of 625 aged 6- to 13-year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist ( CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain-derived neurotrophic factor, cytokines ( IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-α), chemokines (eotaxin/ CCL11, IP-10, MCP-1), cytokine receptors ( sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. Results We found significant associations between sTNFR2, eotaxin/ CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. Conclusion Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders. [ABSTRACT FROM AUTHOR]

The variation of different physicochemical parameters related to yerba maté quality (caffeine, water extract, total polyphenol content, color parameters and antioxidant activity) was studied in yerba maté samples obtained by three different aging methods: (1) natural aging ( NA); (2) temperature-controlled aging ( TCA); and (3) humidity- and temperature-controlled aging ( HTCA). Adsorption isotherms at low temperatures (20, 30, 40 and 50C) were also determined. Water extract and color parameters ( L and a) increased significantly during aging in the three methods studied ( P < 0.05). The results also showed that during NA the polyphenol content of yerba maté diminished ( P < 0.05), while caffeine remained constant ( P > 0.05). The antioxidant activities of yerba maté obtained by NA and HTCA were significantly higher ( P < 0.05) than the antioxidant activity of yerba maté without aging and the yerba maté obtained by TCA. These variations were explained by 0, 1 and 2 kinetic order equations. Kinetic rate constants were higher in the HTCA than in the TCA, and these values were higher than in the NA according to temperature decrease. Experimental data of equilibrium moisture content at different temperatures showed good fitting ( P < 0.05) with the three models tested ( GAB, Halsey and Henderson). No significant differences were found either with temperature or with the materials obtained using different aging methods. Although the results obtained demonstrate that different aging methods originate similar products, HTCA method is better because it provides a yerba maté with higher total polyphenol content. Practical Applications Aging is one stage in yerba maté ( I lex paraguariensis) processing. There are three methods commonly used to age yerba maté in industry, in which different air conditions (temperature and humidity) are employed. Sensorial analysis, usually carried out by expert tasters, is commonly used to control the aging method and the degree of aging of yerba maté. These tests are subjective and suffer from inconsistency and inaccuracy, so it is necessary to develop objective methods to identify the yerba maté quality, chemically or physically. This work evaluates the variation of different physicochemical parameters during the aging stage of yerba maté in order to differentiate the products obtained using the three aging methods. Data were fitted to different kinetic equations in order to predict the degree of aging and the time necessary to reach the end point. [ABSTRACT FROM AUTHOR]