Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell-derived secretome in preclinical models of morphine dependence.

BACKGROUND: Morphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine-induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms. Due to its rich content in potent anti-inflammatory and antioxidant factors, secretome derived from human mesenchymal stem cells (hMSCs) is proposed as a preclinical therapeutic tool for the treatment of this complex neurological condition associated with neuroinflammation and brain oxidative stress. METHODS: Two animal models of morphine dependence were used to evaluate the therapeutic efficacy of hMSC-derived secretome in reducing morphine withdrawal signs. In the first model, rats were implanted subcutaneously with mini-pumps which released morphine at a concentration of 10 mg/kg/day for seven days. Three days after pump implantation, animals were treated with a simultaneous intravenous and intranasal administration of hMSC-derived secretome or vehicle, and withdrawal signs were precipitated on day seven by i.p. naloxone administration. In this model, brain alterations associated with withdrawal were also analyzed before withdrawal precipitation. In the second animal model, rats voluntarily consuming morphine for three weeks were intravenously and intranasally treated with hMSC-derived secretome or vehicle, and withdrawal signs were induced by morphine deprivation. RESULTS: In both animal models secretome administration induced a significant reduction of withdrawal signs, as shown by a reduction in a combined withdrawal score. Secretome administration also promoted a reduction in morphine-induced neuroinflammation in the hippocampus and nucleus accumbens, while no changes were observed in extracellular glutamate levels in the nucleus accumbens. CONCLUSION: Data presented from two animal models of morphine dependence suggest that administration of secretome derived from hMSCs reduces the development of opioid withdrawal signs, which correlates with a reduction in neuroinflammation in the hippocampus and nucleus accumbens.

Content and Yield of L-DOPA and Bioactive Compounds of Broad Bean Plants: Antioxidant and Anti-Inflammatory Activity In Vitro.

The broad bean plant contains L-DOPA, a compound that is essential for patients with Parkinson's disease. However, little has been reported on other broad bean compounds that have beneficial effects on health. The objective was to evaluate plants of four Mexican broad bean varieties to determine the content and yield of total phenolic compounds (TPC), total flavonoids (TF), and L-DOPA, as well as to analyze the flavonoid profile and antioxidant (AA) and anti-inflammatory (AANTI) activity in vitro. Broad bean seeds were sown in the field and plants were harvested 20 days after emergence. The analyses were performed with visible UV spectrophotometry and HPLC. The variety José María produced the highest yield of TPC (9.30 g m-2), TF (8.08 g m-2), and L-DOPA (5.64 g m-2) per unit of area. The highest yields per plant were obtained with the Rojita variety: TPC (0.25 g plant-1), TF (0.21 g plant-1), and L-DOPA (0.17 g plant-1). This variety also had the highest antioxidant (IC50 = 87.68 µg mL-1) and anti-inflammatory (IC50 = 74.40 mg mL-1) activity, which was attributed to the L-DOPA compounds and to rutin and isoorientins, respectively. The flavonoid profile revealed the presence of rutin and isoorientins, which had not been previously detected in the broad bean plant.

Defining a diverse core collection of the Colombian Central Collection of potatoes: a tool to advance research and breeding.

The highly diverse Colombian Central Collection (CCC) of cultivated potatoes is the most important source of genetic variation for breeding and the agricultural development of this staple crop in Colombia. Potato is the primary source of income for more than 100.000 farming families in Colombia. However, biotic and abiotic challenges limit crop production. Furthermore, climate change, food security, and malnutrition constraints call for adaptive crop development to be urgently addressed. The clonal CCC of potatoes contains 1,255 accessions - an extensive collection size that limits its optimal assessment and use. Our study evaluated different collection sizes from the whole clonal collection to define the best core collection that captures the total genetic diversity of this unique collection, to support a characterization more cost-effectively. Initially, we genotyped 1,141 accessions from the clonal collection and 20 breeding lines using 3,586 genome-wide polymorphic markers to study CCC's genetic diversity. The analysis of molecular variance confirmed the CCC's diversity with a significant population structure (Phi=0.359; p-value=0.001). Three main genetic pools were identified within this collection (CCC_Group_A, CCC_Group_B1, and CCC_Group_B2), and the commercial varieties were located across the pools. The ploidy level was the main driver of pool identification, followed by a robust representation of accessions from Phureja and Andigenum cultivar groups based on former taxonomic classifications. We also found divergent heterozygosity values within genetic groups, with greater diversity in genetic groups with tetraploids (CCC_Group_B1: 0.37, and CCC_Group_B2: 0.53) than in diploid accessions (CCC_Group_A: 0.14). We subsequently generated one mini-core collection size of 3 percent (39 entries) and three further core collections sizes of 10, 15, and 20 percent (i.e., 129, 194, and 258 entries, respectively) from the total samples genotyped. As our results indicated that genetic diversity was similar across the sampled core collection sizes compared to the main collection, we selected the smallest core collection size of 10 percent. We expect this 10 percent core collection to be an optimal tool for discovering and evaluating functional diversity in the genebank to advance potato breeding and agricultural-related studies. This study also lays the foundations for continued CCC curation by evaluating duplicity and admixing between accessions, completing the digitalization of data, and ploidy determination using chloroplast count.

Focal mu-opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain.

Microglia participates in the modulation of pain signaling. The activation of microglia is suggested to play an important role in affective disorders that are related to a dysfunction of the mesocorticolimbic system (MCLS) and are commonly associated with chronic pain. Moreover, there is evidence that mu-opioid receptors (MORs), expressed in the MCLS, are involved in neuroinflammatory events, although the way by which they do it remains to be elucidated. In this study, we propose that MOR pharmacological activation within the MCLS activates and triggers the local release of proinflammatory cytokines and this pattern of activation is impacted by the presence of systemic inflammatory pain. To test this hypothesis, we used in vivo microdialysis coupled with flow cytometry to measure cytokines release in the nucleus accumbens and immunofluorescence of IBA1 in areas of the MCLS on a rat model of inflammatory pain. Interestingly, the treatment with DAMGO, a MOR agonist locally in the nucleus accumbens, triggered the release of the IL1α, IL1ß, and IL6 proinflammatory cytokines. Furthermore, MOR pharmacological activation in the ventral tegmental area (VTA) modified the levels of IBA1-positive cells in the VTA, prefrontal cortex, the nucleus accumbens and the amygdala in a dose-dependent way, without impacting mechanical nociception. Additionally, MOR blockade in the VTA prevents DAMGO-induced effects. Finally, we observed that systemic inflammatory pain altered the IBA1 immunostaining derived from MOR activation in the MSCLS. Altogether, our results indicate that the microglia-MOR relationship could be pivotal to unravel some inflammatory pain-induced comorbidities related to MCLS dysfunction.

Screening and Identification of Coastal Chilean Thraustochytrids for Arachidonic Acid Production: Biotechnological Potential of Ulkenia visurgensis Lng2-Strain.

Thraustochytrids are unicellular heterotrophic marine protists that have been described as producing a high content of polyunsaturated fatty acids (PUFAs). Among them, arachidonic acid (ARA) stands out as a precursor of several mediators of pivotal importance for the immune system. However, the biotechnological potential of thraustochytrids for ARA production has not been developed. The objective of this study is to isolate and identify native strains from different Chilean coastal environments and evaluate in vitro the effect of culture parameters such as C/N ratio (19 and 33) and temperature (15 °C and 23 °C) on biomass production and arachidonic acid content. A total of nine strains were identified and classified into four genera of the Thraustochitridae family. The Lng2 strain with 99% identity belongs to the species Ulkenia visurgenis and was the most prominent one for ARA production. Temperature had an effect on the PUFA profile but not on the ARA content nor on the biomass yield. Additionally, the C/N ratio has been identified as a key parameter. The ARA productivity increased by 92% (from 0.6 to 8.3 ARA mg/g-DW) and its total biomass by 62.7% (from 1.9 to 5.1 g/L) at a high C/N ratio (33) as compared to the control.

Crosstalk between Mu-Opioid receptors and neuroinflammation: Consequences for drug addiction and pain.

Mu-Opioid Receptors (MORs) are well-known for participating in analgesia, sedation, drug addiction, and other physiological functions. Although MORs have been related to neuroinflammation their biological mechanism remains unclear. It is suggested that MORs work alongside Toll-Like Receptors to enhance the release of pro-inflammatory mediators and cytokines during pathological conditions. Some cytokines, including TNF-α, IL-1ß and IL-6, have been postulated to regulate MORs levels by both avoiding MOR recycling and enhancing its production. In addition, Neurokinin-1 Receptor, also affected during neuroinflammation, could be regulating MOR trafficking. Therefore, inflammation in the central nervous system seems to be associated with altered/increased MORs expression, which might regulate harmful processes, such as drug addiction and pain. Here, we provide a critical evaluation on MORs' role during neuroinflammation and its implication for these conditions. Understanding MORs' functioning, their regulation and implications on drug addiction and pain may help elucidate their potential therapeutic use against these pathological conditions and associated disorders.

Genome Sequence Data Reveal at Least Two Distinct Incursions of the Tropical Race 4 Variant of Fusarium Wilt into South America.

The global banana industry is threatened by one of the most devastating diseases: Fusarium wilt of banana. Fusarium wilt of banana is caused by the soilborne fungus Fusarium oxysporum f. sp. cubense (Foc), which almost annihilated the banana production in the late 1950s. A new strain of Foc, known as tropical race 4 (TR4), attacks a wide range of banana varieties, including Cavendish clones, which are the source of 99% of banana exports. In 2019, Foc TR4 was reported in Colombia, and more recently (2021) in Peru. In this study, we sequenced three fungal isolates identified as Foc TR4 from La Guajira (Colombia) and compared them against 19 whole-genome sequences of Foc TR4 publicly available, including four genome sequences recently released from Peru. To understand the genetic relatedness of the Colombian Foc TR4 isolates and those from Peru, we conducted a phylogenetic analysis based on a genome-wide set of single nucleotide polymorphisms (SNPs). Additionally, we compared the genomes of the 22 available Foc TR4 isolates, looking for the presence-absence of gene polymorphisms and genomic regions. Our results reveal that (i) the Colombian and Peruvian isolates are genetically distant, which could be better explained by independent incursions of the pathogen to the continent, and (ii) there is a high correspondence between the genetic relatedness and geographic origin of Foc TR4. The profile of present/absent genes and the distribution of missing genomic regions showed a high correspondence to the clades recovered in the phylogenetic analysis, supporting the results obtained by SNP-based phylogeny.

Robust and efficient software for reference-free genomic diversity analysis of genotyping-by-sequencing data on diploid and polyploid species.

Genotyping-by-sequencing (GBS) is a widely used and cost-effective technique for obtaining large numbers of genetic markers from populations by sequencing regions adjacent to restriction cut sites. Although a standard reference-based pipeline can be followed to analyse GBS reads, a reference genome is still not available for a large number of species. Hence, reference-free approaches are required to generate the genetic variability information that can be obtained from a GBS experiment. Unfortunately, available tools to perform de novo analysis of GBS reads face issues of usability, accuracy and performance. Furthermore, few available tools are suitable for analysing data sets from polyploid species. In this manuscript, we describe a novel algorithm to perform reference-free variant detection and genotyping from GBS reads. Nonexact searches on a dynamic hash table of consensus sequences allow for efficient read clustering and sorting. This algorithm was integrated in the Next Generation Sequencing Experience Platform (NGSEP) to integrate the state-of-the-art variant detector already implemented in this tool. We performed benchmark experiments with three different empirical data sets of plants and animals with different population structures and ploidies, and sequenced with different GBS protocols at different read depths. These experiments show that NGSEP has comparable and in some cases better accuracy and always better computational efficiency compared to existing solutions. We expect that this new development will be useful for many research groups conducting population genetic studies in a wide variety of species.

EEG representation approach based on Kernel Canonical Correlation Analysis highlighting discriminative patterns for BCI applications.

Brain-Computer Interface (BCI) is applied in the study of different cognitive processes or clinical conditions as enhancing cognitive skills, motor rehabilitation, and control. However, many approaches focus on using a robust classifier instead of providing a better feature space. This work develops a feature representation methodology through the kernel canonical correlation analysis to reveal nonlinear relations between filter-banked common spatial patterns (CSP) extracted. Our approach reveals nonlinear relations between ranked filter-banked multi-class CSP features and the labels in a finite-dimensional canonical space. We tested the performance of our methodology on the BCI Competition IV dataset 2a. The introduced feature representation using a classic linear SVM achieves accuracy rates competitive with the state-of-the-art BCI strategies. Besides, the processing pipeline allows identifying the spatial and spectral features driven by the underlying brain activity and best modeling the motor imagery intentions.Clinical relevance- This BCI strategy assesses the nonlinear relationships between time series to improve the interpretation of brain electrical activity, taking into account the spatial and spectral features driven by the underlying brain dynamic.

MultiGWAS: An integrative tool for Genome Wide Association Studies in tetraploid organisms.

The genome-wide association studies (GWASs) are essential to determine the genetic bases of either ecological or economic phenotypic variation across individuals within populations of the model and nonmodel organisms. For this research question, the GWAS replication testing different parameters and models to validate the results' reproducibility is common. However, straightforward methodologies that manage both replication and tetraploid data are still missing. To solve this problem, we designed the MultiGWAS, a tool that does GWAS for diploid and tetraploid organisms by executing in parallel four software packages, two designed for polyploid data (GWASpoly and SHEsis) and two designed for diploid data (GAPIT and TASSEL). MultiGWAS has several advantages. It runs either in the command line or in a graphical interface; it manages different genotype formats, including VCF. Moreover, it allows control for population structure, relatedness, and several quality control checks on genotype data. Besides, MultiGWAS can test for additive and dominant gene action models, and, through a proprietary scoring function, select the best model to report its associations. Finally, it generates several reports that facilitate identifying false associations from both the significant and the best-ranked association Single Nucleotide Polymorphisms (SNPs) among the four software packages. We tested MultiGWAS with public tetraploid potato data for tuber shape and several simulated data under both additive and dominant models. These tests demonstrated that MultiGWAS is better at detecting reliable associations than using each of the four software packages individually. Moreover, the parallel analysis of polyploid and diploid software that only offers MultiGWAS demonstrates its utility in understanding the best genetic model behind the SNP association in tetraploid organisms. Therefore, MultiGWAS probed to be an excellent alternative for wrapping GWAS replication in diploid and tetraploid organisms in a single analysis environment.

Talleres y evaluaciones de proceso: una herramienta que mejora el rendimiento en asignaturas integradas / Workshops and Process Evaluations: Tools that Improve Performance in Integrated Subjects / Workshops e avaliações de processo: uma ferramenta que melhora o rendimento em disciplinas integradas

Resumen Introducción: una tendencia actual en la educación superior es fusionar materias y articular las asignaturas integradas; sin embargo, hay menor rendimiento y un incremento de la reprobación. Se ha descrito como favorable la aplicación de evaluaciones de procesos como instrumentos de enseñanza y aprendizaje en ciencias de la salud, criterio pertinente de considerar en asignaturas de gran volumen de contenidos. El objetivo de este trabajo fue valorar el efecto de la evaluación del proceso sobre una asignatura integrada de anatomía y fisiología en estudiantes de ciencias de la salud y su relación con el rendimiento. Materiales y métodos: estudio experimental con 144 estudiantes de la Escuela de Ciencias de la Salud en la asignatura de Estructura y Función, distribuidos en dos grupos: control y experimental. Se diseñó e implementó una intervención metodológica para evaluar su efecto en el rendimiento académico. Resultados: la intervención del proceso en el grupo control experimental mejoró el rendimiento comparado con el grupo control tanto en el promedio como en las evaluaciones parciales de cada unidad (t-test < 0.05). En el grupo experimental se registró un incremento del rendimiento entre el 59 % y el 83 % de los estudiantes. Adicionalmente, la mejora progresiva modificó la condición de reprobación a aprobación en un 27 % de los estudiantes tras la intervención (Anova: p < 0.05). Conclusión: la incorporación de evaluaciones de proceso parece ser una favorable herramienta para descomprimir las materias, aplicar lo aprendido, realizar seguimiento a las metodologías de estudio y mejorar el rendimiento de los estudiantes.

Abstract Introduction: A current trend in higher education is to merge subjects together to create one integrated or joint subject. However, an important effect of this integration has been reduced student performance and an increase in subject failures. A possible way to combat this issue may be through a favorable relationship that has been described between the application of process evaluations as teaching and learning instruments in health sciences, especially for the subjects that have a large volume of content. The objective of this study was to assess the effect that this evaluation may have on students' performance in the integrated subject of anatomy and physiology in Health Sciences. Materials and methods: This was an experimental study consisting of 144 students from the School of Health Sciences who were studying the subject of Structure and Function and were distributed amongst two groups: control and experimental. A methodological intervention was designed and implemented to assess its effect on academic performance. Results: The intervention of this process in the experimental control group showed an improvement in students' performance compared to that of the control group both in the average and in the partial evaluations of each unit (t-test < 0.05). In the experimental group, there was an increase in performance between 59% and 83% of the total number of students. Additionally, the progressive improvement modified the condition of disapproval to that of approval in 27% of the students after the intervention, Anova p < 0.05. Conclusion: The incorporation of process evaluations seems to be a favorable tool to decompress subjects taught in schools, to apply what students have initially learned, to follow up on the study methodologies, and improve overall student performance.

Resumo Introdução: uma tendência atual na educação superior é fusionar disciplinas e articular as disciplinas integradas; no entanto, há menor desempenho e um incremento da reprovação. Se tem descrito como favorável a aplicado de avaliações de processos como instrumentos de ensino e aprendizagem em ciências da saúde, critério pertinente de considerar em disciplinas de grande volume de conteúdo. O objetivo é valorar o efeito da avaliação do processo sobre uma disciplina integrada de anatomia e fisiologia em estudantes de ciências da saúde e sua relação com o desempenho. Materiais e métodos: estudo experimental com 144 estudantes da Escola de Ciências da Saúde na disciplina de Estrutura e Função, distribuídos em dois grupos: controle e experimental. Se desenhou e implementou uma intervenção metodológica para avaliar seu efeito no desempenho académico. Resultados: a intervenção do processo no grupo controle experimental melhorou o desempenho comparado com o grupo controle tanto na média quanto nas avaliações parciais de cada unidade (t-test < 0.05). No grupo experimental se registrou um incremento do desempenho entre o 59% e o 83% dos estudantes. Adicionalmente, a melhora progressiva modificou a condição de reprovação a aprovação em um 27% dos estudantes após a intervenção (Anova: p < 0.05). Conclusão: a incorporado de avaliações de processo parece ser uma ferramenta favorável para descomprimir as matérias, aplicar o aprendido, realizar seguimento as metodologias de estudo e melhorar o rendimento dos estudantes.

Inheritance of Rootstock Effects in Avocado (Persea americana Mill.) cv. Hass.

Grafting is typically utilized to merge adapted seedling rootstocks with highly productive clonal scions. This process implies the interaction of multiple genomes to produce a unique tree phenotype. However, the interconnection of both genotypes obscures individual contributions to phenotypic variation (rootstock-mediated heritability), hampering tree breeding. Therefore, our goal was to quantify the inheritance of seedling rootstock effects on scion traits using avocado (Persea americana Mill.) cv. Hass as a model fruit tree. We characterized 240 diverse rootstocks from 8 avocado cv. Hass orchards with similar management in three regions of the province of Antioquia, northwest Andes of Colombia, using 13 microsatellite markers simple sequence repeats (SSRs). Parallel to this, we recorded 20 phenotypic traits (including morphological, biomass/reproductive, and fruit yield and quality traits) in the scions for 3 years (2015-2017). Relatedness among rootstocks was inferred through the genetic markers and inputted in a "genetic prediction" model to calculate narrow-sense heritabilities (h 2) on scion traits. We used three different randomization tests to highlight traits with consistently significant heritability estimates. This strategy allowed us to capture five traits with significant heritability values that ranged from 0.33 to 0.45 and model fits (r) that oscillated between 0.58 and 0.73 across orchards. The results showed significance in the rootstock effects for four complex harvest and quality traits (i.e., total number of fruits, number of fruits with exportation quality, and number of fruits discarded because of low weight or thrips damage), whereas the only morphological trait that had a significant heritability value was overall trunk height (an emergent property of the rootstock-scion interaction). These findings suggest the inheritance of rootstock effects, beyond root phenotype, on a surprisingly wide spectrum of scion traits in "Hass" avocado. They also reinforce the utility of polymorphic SSRs for relatedness reconstruction and genetic prediction of complex traits. This research is, up to date, the most cohesive evidence of narrow-sense inheritance of rootstock effects in a tropical fruit tree crop. Ultimately, our work highlights the importance of considering the rootstock-scion interaction to broaden the genetic basis of fruit tree breeding programs while enhancing our understanding of the consequences of grafting.

Prevalence of hospital antibiotic use in Argentina, 2018.

Hospital antibiotic use in Argentina has not been described. We present results of point prevalence surveys on antibiotic use conducted in 109 Argentinian hospitals in November 2018 and submitted to the National Program of Epidemiology and Control of Hospital-Acquired Infections, and we discuss potential areas for improvement.

Expectation of reward differentially modulates executive inhibition.

BACKGROUND: Inhibitory control, a key modulatory component of cognition guiding strategy and behaviour, can be affected by diverse contingencies. We explore here the effect of expectation of reward over behavioural adjustment in a Stop Signal Task modulated by reward. We hypothesize that cognitive control is modulated by different expectation of the reward. METHODS: Participants were allocated to two groups differing in their degree of knowledge in what to expect from rewards. Expected Specific Reward participants (N = 21) were informed of the different monetary feedbacks they would receive after each successful inhibition. Unexpected Reward participants (N = 24) were only told that they would receive monetary reward after correct inhibitory trials, but not the amounts or differences. RESULTS: Our results confirmed previous observations demonstrating a "kick-start effect" where a high reward feedback at the beginning of the task increases response inhibition. The Expected Specific Reward condition seems also to improve inhibitory control -as measured by the stop signal reaction time (SSRT)-, compared to the Unexpected Reward group. CONCLUSIONS: Knowledge of reward magnitudes seems to play a role in cognitive control irrespective of feedback magnitude. The manipulation of reward expectation appears to trigger different strategies for cognitive control, inducing a bottom-up effect of external cues, or a top-down effect given by the anticipation of incoming rewards. This is an early exploration to unearth possible higher order modulators - expectation and motivation- of cognitive control. This approach aims to gain insight into diverse psychopathological conditions related to impulsivity and altered reward systems such as Attention Deficit Hyperactive Disorder (ADHD), personality disorders, substance abuse, pathological gambling and cognitive aspects of Parkinson Disease.

Trastornos psiquiátricos secundarios a enfermedades neurometabólicas / Psychiatric Disorders Secondary to Neurometabolic Disorders

Hay algunas enfermedades secundarias a errores innatos del metabolismo que se asocian a trastornos psiquiátricos o síntomas neurológicos menores. La existencia de algunos pacientes con signos únicamente psiquiátricos representa un desafío diagnóstico y terapéutico. El objetivo del presente artículo es describir 6 enfermedades neurometabólicas tratables que se presentan con síntomas psiquiátricos que camuflan su origen orgánico, con el propósito de que se las tome en cuenta en la consulta psiquiátrica. Se describen los trastornos del metabolismo de la homocisteína y del ciclo de la urea, la enfermedad de Wilson, la enfermedad de Niemann-Pick tipo C, la porfiria aguda y la xantomatosis cerebrotendinosa. El análisis de la literatura lleva a proponer una lista de síntomas psiquiátricos asociados con dichas afecciones, que abarcan desde los cambios insidiosos del afecto y el curso del pensamiento hasta síntomas atípicos, como alucinaciones visuales, efectos paradójicos de los medicamentos antipsicóticos y trastornos del comportamiento de niños y adolescentes que conllevan degradación de la autonomía. Asimismo se listan los signos neurológicos más frecuentemente relacionados, como las alteraciones del estado de conciencia, los trastornos de la conducta motora y el equilibro, la catatonia o el déficit cognitivo progresivo. Se hace hincapié en la importancia de considerar la resistencia al tratamiento antipsicótico como una señal importante para sospechar organicidad y la mejoría significativa de la alteración psiquiátrica cuando se instaura un tratamiento eficaz y precoz.

Some diseases secondary to inborn errors of metabolism are associated with psychiatric, disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease, Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis are described. Following an analysis of the literature, a list of psychiatric symptoms associated with these disorders are proposed, ranging from insidious changes in affective state and thought to atypical symptoms such as visual hallucinations, as well as paradoxical effects of antipsychotics or behavioural disorders in children and adolescents associated with loss of autonomy. The most frequently associated neurological signs, such as alterations in the state of consciousness, motor behaviour and balance disorders, catatonia or progressive cognitive deficit are also listed. Emphasis is placed on the importance of considering resistance to antipsychotic treatment as a warning sign to suspect organicity, as well as the significant improvement in psychiatric impairment when effective and early treatment is established.

Psychiatric Disorders Secondary to Neurometabolic Disorders. / Trastornos psiquiátricos secundarios a enfermedades neurometabólicas.

Some diseases secondary to inborn errors of metabolism are associated with psychiatric disorders or minor neurological symptoms. The existence of some cases with exclusively psychiatric symptoms represents a diagnostic and therapeutic challenge. The aim of this article is to describe seven treatable neurometabolic disorders that should be taken into account in the psychiatric consultation as they manifest with psychiatric symptoms that mask the organic origin of the disorder. Homocysteine metabolism and urea cycle disorders, Wilson's disease, Niemann-Pick disease Type C, acute porphyria and cerebrotendinous xanthomatosis are described. Following an analysis of the literature, a list of psychiatric symptoms associated with these disorders are proposed, ranging from insidious changes in affective state and thought to atypical symptoms such as visual hallucinations, as well as paradoxical effects of antipsychotics or behavioural disorders in children and adolescents associated with loss of autonomy. The most frequently associated neurological signs, such as alterations in the state of consciousness, motor behaviour and balance disorders, catatonia or progressive cognitive deficit are also listed. Emphasis is placed on the importance of considering resistance to antipsychotic treatment as a warning sign to suspect organicity, as well as the significant improvement in psychiatric impairment when effective and early treatment is established.

Development of a Participatory Health Communication Intervention: An Ecological Approach to Reducing Rural Information Inequality and Health Disparities.

A strong and diverse communication infrastructure is essential for communication to improve health. When that infrastructure is weak, health information fails to reach appropriate audiences; this is a component of information inequality that contributes to health disparities. Approaches to addressing information inequality have either focused on individual-level barriers or exclusively on changing the information environment. Largely missing from information inequality interventions is a multilevel, ecological approach consistent with the ways in which information inequality affects health. This study addresses that gap by describing a participatory intervention in a rural, majority-Latino community. Previous work identified a weak information infrastructure as a major barrier to health: Residents struggled to find timely, relevant information, while stakeholders faced challenges knowing how to reach diverse audiences with critical health-related information. We employed participatory health communication asset mapping to identify health communication resources - safe, trusted spaces, and places - that served three distinct communication functions: informational (i.e., where health information can be provided), conversational (i.e., where residents feel comfortable discussing health issues), and connection (i.e., where a relationship exists). Through a six-step process, community leaders and residents identified communication resources and collaborated to create a communication resource map. We discuss how this study advances the theoretical understanding of integration of culture-centered and ecological approaches for communication to reduce health disparities.

Influence of socioeconomic status on antipsychotic prescriptions among youth in France.

BACKGROUND: Recent studies analysing the trends in antipsychotic (AP) prescriptions for children and adolescents have raised concerns regarding the influence of socioeconomic status. Previous findings have also shown variable prescription rates for first-generation (FG) and second-generation (SG) APs. METHOD: Our objectives were to assess the proportion of patients from low-income families receiving APs and the most commonly prescribed APs in France. We conducted a descriptive analysis of AP drugs dispensed during a 1-year period (July 1, 2013-June 30, 2014) in a northwestern region of France with 941,857 subjects less than 18 years old. All data were extracted from an exhaustive, individual and anonymous social security database. We obtained each subject's socioeconomic status (by identifying their affiliation with a specific social security program) and also collected sociodemographic data, drug type, prescribing and dispensing dates and amount, and prescriber type (e.g., hospital physician, general practitioner, psychiatrist, paediatrician). RESULTS: There were two main novel findings. First, we found that the proportion of patients with AP prescriptions was nearly ten times higher in low-income families than in the general population: 35.9% of CMU-C patients compared to 3.7% in all of Pays de la Loire (X 2 = 7875.1, p < 0.001). Additionally, we found a higher rate of FGAP than SGAP prescriptions (65% vs. 57%). CONCLUSIONS: Our study suggests two types of AP misuse that could provide interesting targets for public healthcare interventions. First, our results strongly suggest an over-representation of patients from low-income families. Low-income families primarily resided in areas with low physician density and appeared to receive drugs to treat their conditions more frequently than other individuals. This increased prescription rate is a public health issue, potentially requiring political action. Second, the use of FGAPs did not adhere to the latest recommendations for drug use in this population, and this discrepancy should be addressed with informational campaigns targeted to medical practitioners.

Fluoride affects bone repair differently in mice models with distinct bone densities.

We grouped mice [strains: C57BL/6J (n=32) and C3H/HeJ (n=32)] to address the influence of bone density on fluoride's (F's) biological effects. These animals received low-fluoride food and water containing 0 (control group) or 50ppm of F for up to 28days. The upper left central incisor was extracted, and the left maxilla was collected at 7, 14, 21, and 28days for histological and histomorphometric analysis to estimate bone neoformation. Our results showed bone neoformation in all of the evaluated groups, with the presence of bone islets invading the center of the alveoli when replacing the existing connective tissue. Curiously, this biological phenomenon was more evident in the C57BL/6J strain. The histomorphometric analysis confirmed the histological findings in relation to the amount of new bone tissue and showed a decrease in C3H/HeJ mice (control group). Altogether, our results showed differential effects of fluoride bone metabolism, confirming a genetic component in susceptibility to the effects of fluoride.

Predicting RAD-seq Marker Numbers across the Eukaryotic Tree of Life.

High-throughput sequencing of reduced representation libraries obtained through digestion with restriction enzymes--generically known as restriction site associated DNA sequencing (RAD-seq)--is a common strategy to generate genome-wide genotypic and sequence data from eukaryotes. A critical design element of any RAD-seq study is knowledge of the approximate number of genetic markers that can be obtained for a taxon using different restriction enzymes, as this number determines the scope of a project, and ultimately defines its success. This number can only be directly determined if a reference genome sequence is available, or it can be estimated if the genome size and restriction recognition sequence probabilities are known. However, both scenarios are uncommon for nonmodel species. Here, we performed systematic in silico surveys of recognition sequences, for diverse and commonly used type II restriction enzymes across the eukaryotic tree of life. Our observations reveal that recognition sequence frequencies for a given restriction enzyme are strikingly variable among broad eukaryotic taxonomic groups, being largely determined by phylogenetic relatedness. We demonstrate that genome sizes can be predicted from cleavage frequency data obtained with restriction enzymes targeting "neutral" elements. Models based on genomic compositions are also effective tools to accurately calculate probabilities of recognition sequences across taxa, and can be applied to species for which reduced representation data are available (including transcriptomes and neutral RAD-seq data sets). The analytical pipeline developed in this study, PredRAD (https://github.com/phrh/PredRAD), and the resulting databases constitute valuable resources that will help guide the design of any study using RAD-seq or related methods.