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Roberto Gonzalez-Salinas,1,2 Adriano Guarnieri,3 María Concepción Guirao Navarro,3 Manuel Saenz-de-Viteri3 1Department of Biomedical Research, Universidad Autónoma de Querétaro, Querétaro, Mexico; 2Department of Research, Asociación para Evitar la Ceguera en México, Mexico City, Mexico; 3Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain Abstract: Cataract, a degradation of the optical quality of the crystalline lens, progressive and age-related, is the leading cause of treatable blindness worldwide. Cataract surgery is the most common surgical procedure performed by ophthalmologists and is the only effective treatment for cataracts. Advances in the surgical techniques and better postoperative visual outcomes have progressively changed the primary concern of cataract surgery to become a procedure refined to yield the best possible refractive results. Sufficient mydriasis during cataract removal is critical to a successful surgical outcome. Poor pupil dilation can lead to serious sight-threatening complications that significantly increase the cost of surgery and decrease patients comfort. Mydriasis is obtained using anticholinergic and sympathomimetic drugs. Phenylephrine, an α1-adrenergic receptor agonist, can efficiently dilate the pupil when administered by intracameral injection. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) like ketorolac, which inhibit the synthesis of prostaglandins, are used to decrease intraoperative miosis, control pain and inflammation associated with cataract surgery, and to prevent the development of cystoid macular edema following surgery. Recently, a new combination of phenylephrine and ketorolac (Omidria®) has been approved by United States Food and Drug Administration for use during cataract surgery to maintain intraoperative mydriasis, prevent miosis, and reduce postoperative pain and inflammation. Clinical trials have shown that this new combination is effective, combining the positive effects of both drugs with a good safety profile and patient tolerability. Moreover, recent reports suggest that this combination is also effective in patients with high risk of poor pupil dilation. In conclusion, cataract is a global problem that significantly affects patients’ quality of life. However, they can be managed with a safe and minimally invasive surgery. Advances in surgical techniques and newer pharmacological agents such as the combination of phenylephrine and ketorolac, together with better intraocular lenses, have greatly improved visual outcomes and thus patients’ expectations regarding visual recovery are also increasing. Keywords: cataract surgery, mydriasis, phenylephrine, ketorolac, Omidria®

In view of the lack of an effective pharmacological treatment against human anisakiosis, a disease produced by L(3) larvae of the genus Anisakis present in raw fish, we studied the in vivo larvicidal effect of certain monoterpenic derivatives against L(3) of A. simplex s.l. The aldehydic monoterpene citral and the alcoholic citronellol, when they are administered together to the larvae of the nematode at the concentration of 46.90 mg/0.5 ml in olive oil, achieve 85.90% and 67.53% dead L(3), respectively, and also stop rats suffering gastrointestinal hemorrhages produced by the larvae. [ABSTRACT FROM AUTHOR]

Importance: Depression is a leading cause of disability. The timing and persistence of depression may be differentially associated with long-term mental health and psychosocial outcomes., Objective: To examine if depression symptoms during early and middle childhood and adolescence and persistent depression symptoms are associated with impaired young adult outcomes independent of early risk factors., Design, Setting, and Participants: Data for this prospective, longitudinal cohort study were from the Québec Longitudinal Study of Child Development, a representative population-based Canadian birth cohort. The cohort consists of infants born from October 1, 1997, to July 31, 1998. This is an ongoing study; data are collected annually or every 2 years and include those ages 5 months to 21 years. The end date for the data in this study was June 30, 2019, and data analyses were performed from October 4, 2022, to January 3, 2024., Exposures: Depression symptoms were assessed using maternal reports in early childhood (ages 1.5 to 6 years) from 1999 to 2004, teacher reports in middle childhood (ages 7 to 12 years) from 2005 to 2010, and self-reports in adolescence (ages 13 to 17 years) from 2011 to 2015., Main Outcomes and Measures: The primary outcome was depression symptoms at age 20 years, and secondary outcomes were indicators of psychosocial functioning (binge drinking; perceived stress; not being in education, employment, or training; social support; and experiencing online harrasment) at age 21 years. All outcomes were self-reported. Adult outcomes were reported by participants at ages 20 and 21 years from 2017 to 2019. Risk factors assessed when children were aged 5 months old were considered as covariates to assess the independent associations of childhood and adolescent depression symptoms with adult outcomes., Results: The cohort consisted of 2120 infants. The analytic sample size varied from 1118 to 1254 participants across outcomes (56.85% to 57.96% female). Concerning the primary outcome, adjusting for early risk factors and multiple testing, depression symptoms during adolescence were associated with higher levels of depression symptoms (β, 1.08 [95% CI, 0.84-1.32]; P < .001 unadjusted and Bonferroni adjusted) in young adulthood. Concerning the secondary outcomes, depression symptoms in adolescence were only associated with perceived stress (β, 3.63 [95% CI, 2.66-4.60]; P < .001 unadjusted and Bonferroni adjusted), while both middle-childhood (β, -1.58 [95% CI, -2.65 to -0.51]; P = .003 unadjusted and P < .001 Bonferroni adjusted) and adolescent (β, -1.97 [95% CI, -2.53 to -1.41]; P < .001 unadjusted and Bonferroni adjusted) depression symptoms were associated with lower levels of social support. There were no associations for binge drinking; not being in education, employment, or training; or experiencing online harrasment., Conclusions and Relevance: In this cohort study of Canadian children and adolescents, childhood and adolescent depression symptoms were associated with impaired adult psychosocial functioning. Interventions should aim to screen and monitor children and adolescents for depression to inform policymaking regarding young adult mental health and psychosocial outcomes.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment., (© 2024. The Author(s).)

Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer-related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high-risk cases often confront therapeutic resistance and relapse. Here, we explore the aryl hydrocarbon receptor (AHR), a versatile transcription factor implicated in diverse physiological functions such as xenobiotic response, immune modulation, and cell growth. Despite its varying roles in malignancies, AHR's involvement in neuroblastoma remains elusive. Our study investigates the interplay between AHR and its ligand kynurenine (Kyn) in neuroblastoma cells. Kyn is generated from tryptophan (Trp) by the activity of the enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2). We found that neuroblastoma cells displayed sensitivity to the TDO2 inhibitor 680C91, exposing potential vulnerabilities. Furthermore, combining TDO2 inhibition with retinoic acid or irinotecan (two chemotherapeutic agents used to treat neuroblastoma patients) revealed synergistic effects in select cell lines. Importantly, clinical correlation analysis using patient data established a link between elevated expression of Kyn-AHR pathway genes and adverse prognosis, particularly in older children. These findings underscore the significance of the Kyn-AHR pathway in neuroblastoma progression, emphasizing its potential role as a therapeutic target., (© 2024 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Socioeconomic status (SES) influences the risk of both physical diseases, such as asthma, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). Using Causal Mediation Analysis on French birth-cohort data, we found a causal pathway from SES to ADHD symptoms, in part mediated by asthma. An increase in family income at age 3 by one unit resulted in lower ADHD symptoms at age 5, by -0.37 [95% CI: -0.50, -0.24] SDQ-score-points, with additional -0.04 [95% CI: -0.08, -0.01] points reduction indirectly via asthma at age 3, both with statistical significance. Importantly, family income at age 3 exerted both direct and indirect (via asthma) negative effects on later ADHD symptoms with much higher magnitudes for the direct effect. Our findings underscore the importance of apprehending ADHD symptoms in the broader context of socioeconomic disparities, along with their comorbidities with asthma, potentially influencing public health interventions and clinical practice in managing ADHD., (© 2024. The Author(s).)

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Balneotherapy has demonstrated clinical efficacy in the management of pathologies involving low-grade inflammation and stress. In rheumatic conditions such as osteoarthritis (OA), this therapy presents anti-inflammatory properties and potential to improve psychological well-being. Although the neurohormones serotonin and dopamine are known to be involved in these processes, surprisingly they have not been studied in this context. The objective was to evaluate the effect of a cycle of balneotherapy with peloids (pelotherapy) on circulating serotonin and dopamine concentrations in a group of aged individuals with OA, after comparing their basal state to that of an age-matched control group. In our pilot study, a pelotherapy program (10 days) was carried out in a group of 16 elderly patients with OA, evaluating its effects on circulating serotonin and dopamine concentrations (measured by ELISA). Individuals with OA showed higher levels of serotonin and lower dopamine levels, in line with the inflammatory roles of these mediators. After pelotherapy, serotonin concentrations significantly decreased, potentially contributing to the previously reported anti-inflammatory effects of balneotherapy., (© 2023. The Author(s).)

Increased nucleolar size and activity correlate with aberrant ribosome biogenesis and enhanced translation in cancer cells. One of the first and rate-limiting steps in translation is the interaction of the 40S small ribosome subunit with mRNAs. Here, we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small ribosome subunit. ZNF692 forms a hub containing the exosome complex and ribosome biogenesis factors specialized in the final steps of 18S rRNA processing and 40S ribosome maturation in the granular component of the nucleolus. Highly proliferative cells are more reliant on ZNF692 than normal cells; thus, we conclude that effective production of small ribosome subunits is critical for translation efficiency in cancer cells., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The aim of our study was to describe the prevalence of burnout syndrome (BOS) in paediatricians working in paediatric emergency care settings and to analyse its association with potential risk factors., Material and Methods: Multicentre cross-sectional study through a survey of paediatricians working in paediatric emergency care settings in hospitals affiliated to the Research Network of the Spanish Society of Paediatric Emergency Medicine (SEUP) between September 2019 and January 2020. We analysed the association between social/family-related, demographic, occupational and satisfaction factors and the presence of BOS by means of multivariate and multilevel mixed-effects logistic regression models., Results: The estimated prevalence of BOS was 36.5% (95% confidence interval [CI], 31.7 %-41.2%). In the multivariate analysis, lacking a stable group of friends (OR, 2.57; 95% CI, 1.10-5.97), problems in and out of the work setting (OR, 3.06; 95% CI, 1.60-5.88) and a work experience of 9 years or less (OR, 2.31; 95% CI, 1.37-3.90) were identified as individual factors that increased the risk of SBO, while feeling acknowledged by coworkers (OR, 0.48; 95% CI, 0.30-0.79) and acknowledged by one's supervisor (OR, 0.62; 95% CI, 0.41-0.93) were protective factors. In relation to the hospital, the paediatric emergency unit being a subdepartment of the Department of Paediatrics (OR, 3.81; 95% CI, 1.85-7.85), the presence of an on-call emergency medicine specialist around the clock (OR, 3.53; 95% CI,1.62-7.73) and a volume of 28 or more paediatric emergency encounters a day to be managed per on-call physician (OR, 2.05; 95% CI, 1.01-4.16) were identified as independent risk factors for SBO. There was no variability in the prevalence of BOS attributable to differences between hospitals and autonomous communities, save for the described situations., Conclusions: The prevalence of SBO among these providers is high. There are modifiable factors that we can intervene on to address BOS, independently of the hospital or region., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Pain and the anxiety that it produces are the main sources of suffering in children managed in emergency departments, eliciting a growing interest in parents and health care providers in the adequate provision of sedation and analgesia. In consequence, the number of diagnostic and therapeutic procedures that require sedation and/or analgesia in paediatric emergency departments has increased in recent years, which has generated a need to train non-anaesthesiologists on how to provide this care without affecting patient safety. The objective of this document is to establish evidence-based recommendations, developed by consensus by the Working Group on Sedation and Analgesia of the Sociedad Española de Urgencias de Pediatría, regarding the competencies and training of staff who perform sedation or analgesia procedures to achieve the greatest possible quality in the management of paediatric patients before, during and after these procedures in the paediatric emergency care setting. The consensus document has been structured in two parts: the first addresses the competencies of non-anaesthesiologists who perform sedoanalgesia procedures, and the second how to obtain the necessary training. A list of research questions was prepared, keywords defined and a literature search carried out to break down and summarise the available evidence. The results are presented in the form of conclusions, which were subjected to anonymous voting by each of the members of the working group. For each of the conclusions, we provide the percent agreement obtained in the voting., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) regulates cellular detoxification, proliferation and immune evasion in a range of cell types and tissues, including cancer cells. In this study, we used RNA-sequencing to identify the signature of the AHR target genes regulated by the pollutant 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and the endogenous ligand kynurenine (Kyn), a tryptophan-derived metabolite. This approach identified a signature of six genes (CYP1A1, ALDH1A3, ABCG2, ADGRF1 and SCIN) as commonly activated by endogenous or exogenous ligands of AHR in multiple colon cancer cell lines. Among these, the actin-severing protein scinderin (SCIN) was necessary for cell proliferation; SCIN downregulation limited cell proliferation and its expression increased it. SCIN expression was elevated in a subset of colon cancer patient samples, which also contained elevated β-catenin levels. Remarkably, SCIN expression promoted nuclear translocation of β-catenin and activates the WNT pathway. Our study identifies a new mechanism for adhesion-mediated signaling in which SCIN, likely via its ability to alter the actin cytoskeleton, facilitates the nuclear translocation of β-catenin. This article has an associated First Person interview with the first authors of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Pain in children population is prevalent, but its proper diagnosis and management are frequently insufficient in pediatrics daily practice. Lack of knowledge of the professionals in charge is a recognized barrier to ensure an appropiate approach to pain in this population. Our present study reflects the current status of pain management and the challenges in diagnosis and treatment that pediatricians face in their daily work. This information is obtained from a survey made with a voluntary questionaire, desinged and distributed online by "Grupo Español para el Estudio del Dolor Pediátrico (GEEDP)" to pediatricians in Spain from october 2021 to march 2022. The final objective of the questionaire was to shed some light into the problem and find out which areas of pain management knowledge are in need of improvent., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

The nucleolus harbors the machinery necessary to produce new ribosomes which are critical for protein synthesis. Nucleolar size, shape, and density are highly dynamic and can be adjusted to accommodate ribosome biogenesis according to the needs for protein synthesis. In cancer, cells undergo continuous proliferation; therefore, nucleolar activity is elevated due to their high demand for protein synthesis. The transcription factor and universal oncogene MYC promotes nucleolar activity by enhancing the transcription of ribosomal DNA (rDNA) and ribosomal proteins. This review summarizes the importance of nucleolar activity in mammalian cells, MYC's role in nucleolar regulation in cancer, and discusses how a better understanding (and the potential inhibition) of aberrant nucleolar activity in cancer cells could lead to novel therapeutics.

Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept "bioregulation of inflammatory/innate responses" was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual's inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.

Introduction: A cross-sectional descriptive study was conducted to evaluate the factor structure of Spanish translation and adaptation of the Cognitive Flexibility Inventory (CFI) in a sample of Colombian adults., Method: The sample of the study was n = 968. Respondents were aged between 18 and 52 years old (Mage=22.81, SD=4.42). Descriptive analyses, confirmatory factor analysis, and Cronbach's Alpha calculation were carried out., Results: Internal consistency for the global scale was high (α=.89). Likewise, the coefficients of the Alternative factor and the Control factor were similar (α=.90, 95% CI=.89-.90 and α=.83, 95% CI=.81-.85, respectively). A two-factor structure performed best according to the results of model selection criteria. This model suggested the existence of two correlated factors, with correlated items within factors (Item19 Item20 and Item8 Item10)., Conclusions: Overall, the results suggest that the CFI scale exhibits construct validity and adequate reliability, both for the general scale and the subscales in the Colombian sample, enabling their use in contexts such as clinical or research., Competing Interests: Conflict of interests: The authors have declared that there is no conflict of interest.

The Mediterranean fruit fly, Ceratitis capitata (Wied.), is an endemic pest in fruit-growing areas of the Spanish Mediterranean coast. In the Valencian Community, it represents a serious problem in the cultivation of citrus and numerous species of fruit, such as peach, cherry, apricot, persimmon, etc. For over 50 years, the Department of Agriculture of Valencia has led, promoted, and carried out a C. capitata control programme to protect crops, especially citrus fruits, because this community is the largest national producer and the leading region for fresh citrus exports in the world. Traditionally, pest control has been based on the use of insecticides. However, a reduction of more than 90% of a target wild population was achieved in the frame of a pilot integrated pest management (IPM) project based on the sterile insect technique (SIT), which was implemented from 2003 to 2006. Based on this successful result, in 2007 the Department of Agriculture of Valencia initiated an area-wide integrated pest management (AW-IPM) programme for the suppression of C. capitata , using the SIT as the primary control method. Complementary activities are implemented periodically in hotspots and during different time periods depending on the pest population dynamics. As a result, there has been a reduction of more than 90% in the use of insecticides by aerial means to control C. capitata , as well as a growth trend in exports of citrus and fresh fruits from the Valencian Community in recent years. This paper provides a historical review of the Valencian programme and briefly describes how technological innovations and decision-making tools have contributed to programme efficiency.

Importance: Although longitudinal studies have reported associations between early life factors (ie, in-utero/perinatal/infancy) and long-term suicidal behavior, they have concentrated on 1 or few selected factors, and established associations, but did not investigate if early-life factors predict suicidal behavior., Objective: To identify and evaluate the ability of early-life factors to predict suicide attempt in adolescents and young adults from the general population., Design, Setting, and Participants: This prognostic study used data from the Québec Longitudinal Study of Child Development, a population-based longitudinal study from Québec province, Canada. Participants were followed-up from birth to age 20 years. Random forest classification algorithms were developed to predict suicide attempt. To avoid overfitting, prediction performance indices were assessed across 50 randomly split subsamples, and then the mean was calculated. Data were analyzed from November 2019 to June 2020., Exposures: Factors considered in the analysis included 150 variables, spanning virtually all early life domains, including pregnancy and birth information; child, parents, and neighborhood characteristics; parenting and family functioning; parents' mental health; and child temperament, as assessed by mothers, fathers, and hospital birth records., Main Outcomes and Measures: The main outcome was self-reported suicide attempt by age 20 years., Results: Among 1623 included youths aged 20 years, 845 (52.1%) were female and 778 (47.9%) were male. Models show moderate prediction performance. The areas under the curve for the prediction of suicide attempt were 0.72 (95% CI, 0.71-0.73) for females and 0.62 (95% CI, 0.60-0.62) for males. The models showed low sensitivity (females, 0.50; males, 0.32), moderate positive predictive values (females, 0.60; males, 0.62), and good specificity (females, 0.76; males, 0.82) and negative predicted values (females, 0.75; males, 0.71). The most important factors contributing to the prediction included socioeconomic and demographic characteristics of the family (eg, mother and father education and age, socioeconomic status, neighborhood characteristics), parents' psychological state (specifically parents' antisocial behaviors) and parenting practices. Birth-related variables also contributed to the prediction of suicidal behavior (eg, prematurity). Sex differences were also identified, with family-related socioeconomic and demographic characteristics being the top factors for females and parents' antisocial behavior being the top factor for males., Conclusions and Relevance: These findings suggest that early life factors contributed modestly to the prediction of suicidal behavior in adolescence and young adulthood. Although these factors may inform the understanding of the etiological processes of suicide, their utility in the long-term prediction of suicide attempt was limited.

In recent decades, hyperthermia has been used to raise oxygenation levels in tumours undergoing other therapeutic modalities, of which radiotherapy is the most prominent one. It has been hypothesized that oxygenation increases would come from improved blood flow associated with vasodilation. However, no test has determined whether this is a relevant assumption or other mechanisms might be acting. Additionally, since hyperthermia and radiotherapy are not usually co-administered, the crucial question arises as to how temperature and perfusion in tumours will change during and after hyperthermia. Overall, it would seem necessary to find a research framework that clarifies the current knowledge, delimits the scope of the different effects and guides future research. Here, we propose a simple mathematical model to account for temperature and perfusion dynamics in brain tumours subjected to regional hyperthermia. Our results indicate that tumours in well-perfused organs like the brain might only reach therapeutic temperatures if their vasculature is highly disrupted. Furthermore, the characteristic times of return to normal temperature levels are markedly shorter than those required to deliver adjuvant radiotherapy. According to this, a mechanistic coupling of perfusion and temperature would not explain any major oxygenation boost in brain tumours immediately after hyperthermia., Competing Interests: We declare we have no competing interests., (© 2021 The Authors.)

MNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix-loop-helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional regulator beyond the binding to MAX remain unexplored. Here we demonstrate a novel MAX-independent protein interaction between MNT and REL, the oncogenic member of the NF-κB family. REL participates in important biological processes and it is altered in a variety of tumors. REL is a transcription factor that remains inactive in the cytoplasm in an inhibitory complex with IκB and translocates to the nucleus when the NF-κB pathway is activated. In the present manuscript, we show that MNT knockdown triggers REL translocation into the nucleus and thus the activation of the NF-κB pathway. Meanwhile, MNT overexpression results in the repression of IκBα, a bona fide REL target. Both MNT and REL bind to the IκBα gene on the first exon, suggesting its regulation as an MNT-REL complex. Altogether our data indicate that MNT acts as a repressor of the NF-κB pathway by two mechanisms: (1) retention of REL in the cytoplasm by MNT interaction, and (2) MNT-driven repression of REL-target genes through an MNT-REL complex. These results widen our knowledge about MNT biological roles and reveal a novel connection between the MYC/MXD and NF-κB pathways, two of the most prominent pathways in cancer.

Glioblastoma is the most common and aggressive type of cancer in the brain; its poor prognosis is often marked by reoccurrence due to resistance to the chemotherapeutic agent temozolomide, which is triggered by an increase in the expression of DNA repair enzymes such as MGMT. The poor prognosis and limited therapeutic options led to studies targeted at understanding specific vulnerabilities of glioblastoma cells. Metabolic adaptations leading to increased synthesis of nucleotides by de novo biosynthesis pathways are emerging as key alterations driving glioblastoma growth. In this study, we show that enzymes necessary for the de novo biosynthesis of pyrimidines, DHODH and UMPS, are elevated in high grade gliomas and in glioblastoma cell lines. We demonstrate that DHODH's activity is necessary to maintain ribosomal DNA transcription (rDNA). Pharmacological inhibition of DHODH with the specific inhibitors brequinar or ML390 effectively depleted the pool of pyrimidines in glioblastoma cells grown in vitro and in vivo and impaired rDNA transcription, leading to nucleolar stress. Nucleolar stress was visualized by the aberrant redistribution of the transcription factor UBF and the nucleolar organizer nucleophosmin 1 (NPM1), as well as the stabilization of the transcription factor p53. Moreover, DHODH inhibition decreased the proliferation of glioblastoma cells, including temozolomide-resistant cells. Importantly, the addition of exogenous uridine, which reconstitutes the cellular pool of pyrimidine by the salvage pathway, to the culture media recovered the impaired rDNA transcription, nucleolar morphology, p53 levels, and proliferation of glioblastoma cells caused by the DHODH inhibitors. Our in vivo data indicate that while inhibition of DHODH caused a dramatic reduction in pyrimidines in tumor cells, it did not affect the overall pyrimidine levels in normal brain and liver tissues, suggesting that pyrimidine production by the salvage pathway may play an important role in maintaining these nucleotides in normal cells. Our study demonstrates that glioblastoma cells heavily rely on the de novo pyrimidine biosynthesis pathway to generate ribosomal RNA (rRNA) and thus, we identified an approach to inhibit ribosome production and consequently the proliferation of glioblastoma cells through the specific inhibition of the de novo pyrimidine biosynthesis pathway., Competing Interests: The authors have declared that no competing interests exist.

The transcription factor AHR (aryl hydrocarbon receptor) drives the expression of genes involved in detoxification pathways in cells exposed to pollutants and other small molecules. Moreover, AHR supports transcriptional programs that promote ribosome biogenesis and protein synthesis in cells stimulated to proliferate by the oncoprotein MYC. Thus, AHR is necessary for the proliferation of MYC-overexpressing cells. To define metabolic pathways in which AHR cooperates with MYC in supporting cell growth, here we used LC-MS-based metabolomics to examine the metabolome of MYC-expressing cells upon AHR knockdown. We found that AHR knockdown reduced lactate, S-lactoylglutathione, N -acetyl-l-alanine, 2-hydroxyglutarate, and UMP levels. Using our previously obtained RNA sequencing data, we found that AHR mediates the expression of the UMP-generating enzymes dihydroorotate dehydrogenase ( quinone ) ( DHODH ) and uridine monophosphate synthetase ( UMPS ), as well as lactate dehydrogenase A ( LDHA ), establishing a mechanism by which AHR regulates lactate and UMP production in MYC-overexpressing cells. AHR knockdown in glioblastoma cells also reduced the expression of LDHA (and lactate), DHODH , and UMPS but did not affect UMP levels, likely because of compensatory mechanisms in these cells. Our results indicate that AHR contributes to the regulation of metabolic pathways necessary for the proliferation of transformed cells., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Lafita-Navarro et al.)

Semantic memory (SM) is a type of long-term memory associated with the storage of general information about the world. Here we assessed the characteristics of the SM battery, developed by Catricalà et al. (2013), in a sample of Colombian children. This battery was originally conceived to evaluate adults, and features six subtests that assess SM in different modalities, using a common set of 48 stimuli in both living and nonliving categories. The design of the current study is of a cross-sectional and exploratory type. The sample was composed of 111 children, 57 boys (51%) and 54 girls (49%), who were 6 ( n = 68) and 7 ( n = 43) years old and had no intellectual disability. Robust linear regression models and correlation networks were used. We found an effect of age on general intelligence after correcting for gender, and no differences on the six subtest scores after corrections for gender and age were performed. Furthermore, age was found to be positively associated with the naming of colored photographs ( β = . 75, p = . 039), naming in response to an oral description ( β = 1 . 81, p = . 039), picture sorting at four levels ( β = 7 . 22, p = . 029), and sentence verification ( β = 26 . 66, p = . 01). In addition, there were differences between the results obtained in adults in the original study and in the children of our study. This exploratory study supports the feasibility of the Spanish translation of the Catricalà et al. (2013) battery to assess SM in children with a nonclinical condition. Future studies are needed to evaluate the psychometric properties of this SM battery, and to corroborate and expand our findings in a larger sample of control children, and in children with some degree of intellectual disability or suffering of some neurodegenerative or psychiatric conditions.

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor. Upon E-box binding, the MYC-MAX dimer activates gene expression. MNT also binds to the MAX dimerization protein MLX (MLX), and MNT-MLX and MNT-MAX dimers co-exist. However, all MNT functions have been attributed to MNT-MAX dimers, and no functions of the MNT-MLX dimer have been described. MNT's biological role has been linked to its function as a MYC oncogene modulator, but little is known about its regulation. We show here that MNT localizes to the nucleus of MAX-expressing cells and that MNT-MAX dimers bind and repress the MNT promoter, an effect that depends on one of the two E-boxes on this promoter. In MAX-deficient cells, MNT was overexpressed and redistributed to the cytoplasm. Interestingly, MNT was required for cell proliferation even in the absence of MAX. We show that in MAX-deficient cells, MNT binds to MLX, but also forms homodimers. RNA-sequencing experiments revealed that MNT regulates the expression of several genes even in the absence of MAX, with many of these genes being involved in cell cycle regulation and DNA repair. Of note, MNT-MNT homodimers regulated the transcription of some genes involved in cell proliferation. The tight regulation of MNT and its functionality even without MAX suggest a major role for MNT in cell proliferation., (© 2020 Lafita-Navarro et al.)

Background: While regulated WNT activity is required for normal development and stem cell maintenance, mutations that lead to constitutive activation of the WNT pathway cause cellular transformation and drive colorectal cancer. Activation of the WNT pathway ultimately leads to the nuclear translocation of β-catenin which, in complex with TCF/LEF factors, promotes the transcription of genes necessary for growth. The proto-oncogene MYC is one of the most critical genes activated downstream the WNT pathway in colon cancer. Here, we investigate the converse regulation of the WNT pathway by MYC., Methods: We performed RNA-seq analyses to identify genes regulated in cells expressing MYC. We validated the regulation of genes in the WNT pathway including LEF1 by MYC using RT-qPCR, Western blotting, and ChIP-seq. We investigated the importance of LEF1 for the viability of MYC-expressing cells in in fibroblasts, epithelial cells, and colon cells. Bioinformatic analyses were utilized to define the expression of MYC-regulated genes in human colon cancer and metabolomics analyses were used to identify pathways regulated by LEF1 in MYC expressing cells., Results: MYC regulates the levels of numerous WNT-related genes, including the β-catenin co-transcription factor LEF1. MYC activates the transcription of LEF1 and is required for LEF1 expression in colon cancer cells and in primary colonic cells transformed by APC loss of function, a common mutation in colon cancer patients. LEF1 caused the retention of β-catenin in the nucleus, leading to the activation of the WNT pathway in MYC-expressing cells. Consequently, MYC-expressing cells were sensitive to LEF1 inhibition. Moreover, we describe two examples of genes induced in MYC-expressing cells that require LEF1 activity: the peroxisome proliferator activated receptor delta (PPARδ) and the Acyl CoA dehydrogenase 9 (ACAD9)., Conclusions: We demonstrated that MYC is a transcriptional regulator of LEF1 in colonic cells. Our work proposes a novel pathway by which MYC regulates proliferation through activating LEF1 expression which in turn activates the WNT pathway.

Tumors display increased uptake and processing of nutrients to fulfill the demands of rapidly proliferating cancer cells. Seminal studies have shown that the proto-oncogene MYC promotes metabolic reprogramming by altering glutamine uptake and metabolism in cancer cells. How MYC regulates the metabolism of other amino acids in cancer is not fully understood. Using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (LC-MS/MS), we found that MYC increased intracellular levels of tryptophan and tryptophan metabolites in the kynurenine pathway. MYC induced the expression of the tryptophan transporters SLC7A5 and SLC1A5 and the enzyme arylformamidase (AFMID), involved in the conversion of tryptophan into kynurenine. SLC7A5, SLC1A5, and AFMID were elevated in colon cancer cells and tissues, and kynurenine was significantly greater in tumor samples than in the respective adjacent normal tissue from patients with colon cancer. Compared with normal human colonic epithelial cells, colon cancer cells were more sensitive to the depletion of tryptophan. Blocking enzymes in the kynurenine pathway caused preferential death of established colon cancer cells and transformed colonic organoids. We found that only kynurenine and no other tryptophan metabolite promotes the nuclear translocation of the transcription factor aryl hydrocarbon receptor (AHR). Blocking the interaction between AHR and kynurenine with CH223191 reduced the proliferation of colon cancer cells. Therefore, we propose that limiting cellular kynurenine or its downstream targets could present a new strategy to reduce the proliferation of MYC-dependent cancer cells., (© 2019 Venkateswaran et al.; Published by Cold Spring Harbor Laboratory Press.)

Lipases (EC 3.1.1.3) are very used industrial enzymes but presents drawbacks such as lack of stability, and poor recyclability. Most of these obstacles can be solved by lipase immobilization. The objective of this work was evaluated to magnetic magnesium spinel nanoparticles as support for lipase immobilization by covalent bound. The techniques used for nanoparticles synthesis presented advantages in the size selection of the nanoparticles obtained (60-100 nm). The immobilization of Candida rugosa lipase (CRL) was optimized. The optimal conditions were determined to be pH 3.7, enzyme concentration of 1.1 mg/mL at 4 °C and an ionic strength of 100 mM. The CRL@MgFe 2 O 4 activity obtained was 3.2 times over the starting conditions (4.03 U/mL). The immobilization of the lipase on Fe 3 O 4 was evaluated and compared. The activity of the CRL@MgFe 2 O 4 was 61% higher than CRL@Fe 3 O 4 and 22% higher than free enzyme. CRL@MgFe 2 O 4 improved the lipase stability at alkaline pH, hydrophilic solvent and high temperatures. The thermogravimetric analysis showed that this new biocatalyst was more stable compared to the free enzyme. Additionally, the immobilized lipase was recycled by magnetic force and used in ten catalysis cycles. The performance of the recycle was improved using butanol or Triton X 100 during washing. Finally, CRL@FeMg 2 O 4 showed hydrolysis and synthesis activity. Thus, CRL@FeMg 2 O 4 as a novel biocatalyst generation presents interesting properties for industrial applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

MYC enhances protein synthesis by regulating genes involved in ribosome biogenesis and protein translation. Here, we show that MYC-induced protein translation is mediated by the transcription factor aryl hydrocarbon receptor (AHR), which is induced by MYC in colonic cells. AHR promotes protein synthesis by activating the transcription of genes required for ribosome biogenesis and protein translation, including OGFOD1 and NOLC1. Using surface sensing of translation (SUnSET) to measure global protein translation, we found that silencing AHR or its targets diminishes protein synthesis. Therefore, targeting AHR or its downstream pathways could provide a novel approach to limit biomass production in MYC-driven tumors., (© 2018 Lafita-Navarro et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Few empirical studies have been conducted on the continuity of rehabilitation services, despite the fact that it may affect clinical outcomes, patient satisfaction, the perception of quality, and safety., Objectives: The aim of this study was to explore experiences and perceptions of inpatients receiving physical rehabilitation in an acute care hospital and how these experiences may have led to perceived gaps in the continuity of rehabilitation care., Method: Using qualitative research methods, fifteen semi-structured interviews were conducted with patients who received physical rehabilitation during hospital stay in an acute care hospital in Murcia, Spain. Interviews were transcribed verbatim, analyzed, and grouped into predetermined and emergent codes., Results: Patients described three main themes in continuity of care: informational, management, and relational continuity. Several factors were described as influencing the perceived gaps in these three types of continuity. Informational continuity was influenced by the transfer of information among care providers. Relational continuity was influenced by patient-therapist relations and consistency on the part of the provider. Management continuity was influenced by consistency of care between providers and the involvement of patients in their own care., Conclusion: The participants in this study identified several gaps in three types of continuity of care (informational, management, and relational). Inpatients often perceive their experiences of rehabilitation as being disconnected or incoherent over time., (Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.)

MXD1 is a protein that interacts with MAX, to form a repressive transcription factor. MXD1-MAX binds E-boxes. MXD1-MAX antagonizes the transcriptional activity of the MYC oncoprotein in most models. It has been reported that MYC overexpression leads to augmented RNA synthesis and ribosome biogenesis, which is a relevant activity in MYC-mediated tumorigenesis. Here we describe that MXD1, but not MYC or MNT, localizes to the nucleolus in a wide array of cell lines derived from different tissues (carcinoma, leukemia) as well as in embryonic stem cells. MXD1 also localizes in the nucleolus of primary tissue cells as neurons and Sertoli cells. The nucleolar localization of MXD1 was confirmed by co-localization with UBF. Co-immunoprecipitation experiments showed that MXD1 interacted with UBF and proximity ligase assays revealed that this interaction takes place in the nucleolus. Furthermore, chromatin immunoprecipitation assays showed that MXD1 was bound in the transcribed rDNA chromatin, where it co-localizes with UBF, but also in the ribosomal intergenic regions. The MXD1 involvement in rRNA synthesis was also suggested by the nucleolar segregation upon rRNA synthesis inhibition by actinomycin D. Silencing of MXD1 with siRNAs resulted in increased synthesis of pre-rRNA while enforced MXD1 expression reduces it. The results suggest a new role for MXD1, which is the control of ribosome biogenesis. This new MXD1 function would be important to curb MYC activity in tumor cells.

Objectives: To identify clinical characteristics that may lead to the early recognition of patients admitted to the hospital for moderate-to-severe bronchiolitis with urine results associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH)., Patients and Methods: A prospective observational study was conducted, spanning the bronchiolitis epidemic season (October 2012-March 2013), including all children who were admitted to the hospital with a diagnosis of moderate-to-severe bronchiolitis. The following criteria were used to establish a diagnosis of SIADH: urine sodium level of 40 mmol/L or greater, urine osmolarity above 500 mosm/Kg, and urine density of 1020 g/L or greater. Demographic characteristics, ventilation mode and clinical outcome were also analyzed. A comparison was made between those patients that met urine SIADH criteria and those who did not., Results: A total of 126 children were included, and 23 (18.6%) of them had urine SIADH criteria. Patients in this group had a higher incidence of pneumonia and/or atelectasis on chest X-Ray (21.7% vs. 1.9%, P=.002), worse response to bronchodilator treatment with nebulized adrenaline (69,5% vs. 28,1%, P=.016), more need for respiratory assistance (high flow oxygen therapy (17.4% vs. 7.7%, p=.016), or non-invasive mechanical ventilation (13% vs. 5.8%, P=.034), and more admissions to the PICU (26.1% vs. 6.8%, P=.007)., Conclusions: Patients older than one month with acute moderate bronchiolitis and urine SIADH criteria have worse clinical courses and more need for non-invasive mechanical ventilation, PICU admission, and have a higher incidence of pneumonia on chest X-ray. For that reason, it is recommended to collect a urine sample from these patients to allow an early diagnosis of SIADH, and thus early treatment of fluid and electrolyte abnormalities., (Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate the activity of different natural products against L3 larvae of Anisakis type I., Methods: Information on investigations into the activity of natural products against the L3 larvae of Anisakis simplex was collected from scientific journals, books, theses and reports via a library and electronic search (using Pubmed, Scopus, Medline, Web of Science and ScienceDirect). The search terms included: natural products, medicinal plants, essential oils, terpenic derivatives, Anisakis, antinematodal activity., Results: In the literature reviewed numerous papers were found concerning the in vitro and in vivo activity against Anisakis type I of various natural products (plant extracts, essential oils and their major components). Analysis of the results showed that in vitro tests the Melaleuca alternifolia essential oil and the ar-turmerone isolated from Curcuma longa displayed the greatest activity. In vivo, the most active compound was perillaldehyde, the main component of Perilla frutescens essential oil., Conclusions: This study shows that some natural products exhibited promising antianisakis properties., (Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Patient feedback surveys are increasingly seen as a key component of health care quality monitoring and improvement., Objective: The study objective was to describe the development and initial psychometric evaluation of a fixed-length questionnaire about the experiences of patients receiving physical therapist treatment in postacute outpatient settings., Design: This was an instrument development study with validity and reliability testing., Methods: A total of 465 participants attending 3 rehabilitation centers for musculoskeletal conditions completed the questionnaire. A cognitive pretest was applied to the draft version (n=94), and a revised version was evaluated for test-retest reliability (n=90). Analyses to evaluate variance and nonresponse rates for items, the factor structure of the questionnaire, and the metric properties of multi-item scales were conducted., Results: Exploratory factor analyses yielded evidence for a 7-factor structure of the questionnaire, with 3 factors that may be conceptually viewed as professionals' attitudes and behavior (providing information and education, sensitivity to patients' changes, and emotional support) and 4 factors that conceptually reflect organizational environment (duration of attendance, interruptions during care delivery, waiting times, and patient safety). Item-scale correlations ranged from .70 to .93. The percentage of scaling success was 100% for all of the scales. Cronbach alpha coefficients ranged from .70 to .87. Intraclass correlation coefficients ranged from .57 to .80 (median=.68)., Limitations: Generalization to other patients is not known., Conclusions: The questionnaire has test-retest reliability, and the scales have internal consistency and convergent and discriminant validity. All of the scales are distinct and unidimensional., (© 2015 American Physical Therapy Association.)

Objectives: Therapy against anisakiasis requires invasive techniques to extract L3 , and an effective drug against this nematode is needed. The aim of this study was to determine the efficacy of peppermint essential oil (EO) and its main components against the parasite in comparison to albendazole, a drug currently prescribed to treat anisakiasis., Methods: We conducted in vitro experiments and studied an experimental model simulating the human infection in Wistar rats. We used polymerase chain reaction restriction fragment length polymorphism to identify A. simplex s.s. and A. pegreffii and determine any differences in their pathogenicity and susceptibility to the treatments., Results: The in vitro and in vivo experiments both showed that the larvicidal activity of peppermint EO, menthol, menthone and menthyl acetate is higher than that of albendazole. Large stomach lesions were observed in 46.7% of the albendazole-treated rats, whereas no gastrointestinal lesions were detected in those treated with peppermint EO, menthol, menthyl acetate or menthone., Conclusions: In this animal model, treatment with peppermint EO or its main components was more effective than was treatment with albendazole. Lesions were more frequently produced by A. simplex s.s. larvae than by A. pegreffii larvae., (© 2014 John Wiley & Sons Ltd.)

Objective: To assess attitudes and the influence of emotional intelligence is the objective of this work., Method: Nursing professionals answered a questionnaire that assessed the attitude towards suicide and emotional intelligence., Results: The results show a general adverse attitude towards suicidal behavior. The moral dimension of suicide makes the differences between mental health and emergency professionals., Conclusions: Possessing a higher degree of mental health training and a high level of emotional intelligence is associated with a more positive attitude towards patients with suicidal behavior. The formation and development of emotional skills are essential for care delivery to patients with suicidal behavior.

Morphology in chronic HP is characterized by bronchiolocentric mononuclear inflammation, poorly formed granulomas and variable degree of fibrosis. However, recent findings suggest that this disease may present different pathologic patterns. In this study we evaluated the clinical behavior and survival of patients with pigeon breeder's disease according to the pathologic pattern. One-hundred ten biopsies were classified as "typical" (n = 58), non-specific interstitial pneumonia (NSIP)-pattern (n = 22), usual interstitial pneumonia (UIP)-like (n = 10), mixed pattern (n = 9), organizing pneumonia (OP)-pattern (n = 3), airway-centered interstitial fibrosis (ACIF)-pattern (n = 3), and non-classified (n = 5). Clinical features and survival were compared between patients with "typical", NSIP, and UIP patterns. There were no statistical differences between the groups in age, gender, time of symptoms, smoking, clubbing, and PaO(2). By the one-way ANOVA test we found differences in the percent of lymphocytes in bronchoalveolar lavage (BAL; p < 0.002) and in the forced vital capacity (p < 0.05) between the 3 groups. After Bonferroni correction the difference in BAL lymphocytes remained significant among the UIP-like and the typical pattern (36.1 ± 22.9 versus 64.6 ± 20.9, p = 0.001). UIP-like patients exhibited the worst survival rate (HR: 4.19; 95% CI: 1.66-14.47; p < 0.004) while NSIP-like pattern showed the best survival (HR: 0.18; 95% CI: 0.04-0.82; p < 0.03). Multivariate Cox regression analysis revealed that patients with a UIP-like pattern retained a significantly worse survival (HR: 3.4 (IC 95%: 1.15-10.29; p < 0.03), and mortality for the NSIP group was best and approached statistical significance (p = 0.07). These findings demonstrate that a variety of histopathologic and imaging patterns are seen in PBD, and the presence of a UIP-like pattern confers the worst prognosis., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Inflammatory Optic Neuritis (ON) is the most frequent cause of acute visual loss in young adults. Although the visual prognosis is excellent in the majority of cases, many patients develop pathology, such as multiple sclerosis, in its subsequent evolution. The natural history of ON has been studied in numerous works in recent years; one of the most important of which is Optic Neuritis Treatment Trial. Magnetic Resonance plays a fundamental role in the etiological diagnosis of ON and in predicting the risk of conversion into multiple sclerosis. New exploratory techniques have recently been incorporated, such as optical coherence tomography, useful for diagnosis and prognosis; serum biomarkers have been identified in the diagnosis of other pathologies with an autoimmune nature that produce ON. A better understanding of the clinical and exploratory data of typical ON will make a more rapid and accurate diagnostic study possible. Treatment of ON with steroids must be individualised bearing in mind that they do not alter the long-term prognosis and an immunomodulating therapy must be proposed for patients with a high risk of conversion into multiple sclerosis. This article reviews the existing data in the literature on its clinical manifestations, its etiological and differential diagnosis, and the treatment of inflammatory ON.

Acute or sub-acute movement disorders represent a small percentage of neurological emergencies but it is necessary to be aware of their existence because a failure in their diagnosis or treatment can result in significant morbidity and mortality. Clinical presentation of acute movement disorders can be diverse. In some cases acinesia or rigidity predominates, while others are characterized by dystonia, chorea o balism. The type of movement disorder suggest a specific aetiology. Drugs represent the most frequent etiologic factor and are the cause of neuroleptic malignant syndrome and serotoninergic syndrome. Emergencies secondary to Parkinson's disease are reviewed, including parkinsonism-hyperpirexia syndrome, acute psychosis and the emergencies derived from deep brain stimulators. Different aetiologies of acute dystonia and chorea are also covered and, finally, acute movement disorders due to stroke are reviewed.

Transient or persistent loss of vision in one eye is a common and distinctive manifestation of occlusive vascular disease. Occasionally, both eyes are involved together or sequentially, with temporary or even permanent blindness. The internal carotid arteries supply blood to the organ of vision; therefore pathologies of those arteries caused by arteriosclerosis may have a direct influence on its functioning. The most common syndromes are temporary (amaurosis fugax) or constant reduction of visual acuity. In fundus examination central retinal artery occlusion and branch retinal artery occlusion are the most common diagnosis, while retinal vein occlusion, anterior ischemic optic neuropathy, ocular ischemic syndrome are less common. There are many clinical ophtlamological manifestations due to vascular brain damage. Proper recognition and diagnosis of the disease may protect the patient against serious life-threatening complications such as stroke.

This work analyses the way in which various psychosocial risk indicators may predict mobbing. A sample of 638 workers, 168 men and 470 women, from the fruit-and-vegetable sector was evaluated. An anonymous questionnaire was administered to all employees who were present on the evaluation days in the companies comprising the study. After analysing the data obtained with the mobbing questionnaire NAQ-RE (Sáez, García-Izquierdo, and Llor, 2003) and with the psychosocial risk factors evaluation method of the INSHT (Martín and Pérez, 1997), using canonical regression, we found that several psychosocial factors such as role definition, mental workload, interest in the workers, and supervision / participation predict two types of mobbing: personal mobbing and work-performance-related mobbing.

The major risks due to metal pollution of sediments consist of leaching to groundwater and potential toxicity to animals and/or plants. The objective of this study was to evaluate by means of an ecotoxicological approach the effects of the addition of cutting marble sludges on the mobile metal fraction of sediments polluted with heavy metals. The study was carried out on two sediments derived from mining activities in Portman Bay (SE, Spain) polluted by heavy metals. These sediments were mixed with sludges left after the cutting of marble. The results obtained by leaching experiments showed that the addition of marble cutting sludge, consisting mainly of carbonates, to a heavy-metal polluted sediment produces a decrease of available metal forms. The carbonate content seems to play a role in chemical stabilisation of metals and in a decrease of toxicity of sediments. The leached solutions have a non-toxic effect. The mild remediation by addition of sludge has moreover effects to long term.

An in vitro method that simulated the physiological conditions of the digestive process was applied to samples taken from an old mining site, providing information on the levels of metals (Cd, Pb and As) that can be ingested and assimilated by humans. Samples were first characterized by determining pH, texture, mineralogical composition and total metal contents. The mean pH value was 5.4, ranging from 3.1 to 8.4. The mean total metal content for Pb was 2,632+/-59 mg kg(-1), 65+/-1.5 mg kg(-1) for Cd and 279.9+/-9.9 mg kg(-1) for As. Cadmium was the most bioavailable metal both in the stomach and intestinal phases (mean value of 47% and 27.8%, respectively), followed by lead (25.3% and 11.5%) and arsenic (4.9% and 0.5%). A Pearson correlation matrix suggested that pH and mineralogical composition were important factors controlling metal bioavailability from materials in abandoned mining sites.

The capability of an ethanol extract of Rosmarinus tomentosus to protect rat liver in an experimental model of cirrhosis induced by thioacetamide (TAA) has been evaluated. Four groups of rats were used: Two of them received 300 mg TAA/l in the drinking water for 3 months while the other two, which served as controls, were given water ad libitum. During the same period and for each one of the treatments, one group received a semi-purified (SP) diet and the other one was fed the same diet supplemented with 1% of the dry residue obtained from R. tomentosus ethanol extract (SP+E). There was a significant reduction of TAA toxicity in rats fed the SP+E diet, as assessed by plasma and liver biochemical markers, and by liver histopathology. Plasma total protein concentration was restored, urea concentration and plasma alkaline phosphatase and gamma-glutamyl-transferase activities were reduced. A significant correction of plasma fatty acids concentrations was also evident. Hepatic alkaline phosphatase and gamma-glutamyl-transferase activities were significantly reduced in animals fed SP+E diet and glucose-6-phosphatase activity was significantly enhanced. The results suggest that R. tomentosus ethanol extract administered in the diet affords protection against TAA-induced cirrhosis, preventing most of the histological changes and functionality alterations own to this experimental pathology.

Preimplantation embryo development was studied in the golden hamster (Mesocricetus auratus). Three groups of regularly cycling female hamsters were used: (I) 30 nulliparous young female (NYF) hamsters; (II) 24 nulliparous adult female (NAF) hamsters and (III) 30 multiparous adult female (MAF) hamsters. Female hamsters were mated with male hamsters of proven fertility. Only 15 min were allowed for mating. The moment of ejaculation was registered. Female hamsters were killed from 60 to 69 h after coitus. Corpora lutea were counted in both ovarian surfaces. Oviducts and uterine horns were flushed separately and embryo number, stage of development and distribution were recorded. Adult female hamsters, nulliparous and multiparous, had significant higher ovulation rates than NYF, but their reproductive efficiency was significantly lower. Preimplantation embryo development and transport were highly synchronous in NYF, but not in adults. Morulae were observed in NYF as early as 62-63 h after coitus. In adult female hamsters, significant numbers of morulae were found until 66-67 h. On the contrary, in NYF four-cell embryos were detected only until 60-61 h, while four-cell embryos were found until 64-65 h in NAF, and until 66-67 h in MAF. Embryo transport from the oviduct to the uterus is practically completed at 62-63 h after coitus in NYF, while it is evidently retarded in adult animals. In NYF all eight-cell embryos reached the uterus by 62 h after coitus. In adult female hamsters, both nulliparous and multiparous, a considerable number of eight-cell embryos fail to migrate into the uterus even at 67 h after coitus.