Abordaje de los trastornos del sueño en los trastornos del neurodesarrollo / Treatment of sleep disorders in neurodevelopmental disorders

Resumen Los trastornos del sueño son frecuentes en niños y afectan al desarrollo neurológico, con importante repercusión cognitiva, emocional y conductual. Existe una alta prevalencia de trastornos del sueño (TS) en los trastornos del neurodesarrollo (TND), como trastorno del espectro autista (TEA) y trastorno por déficit de atención con hiperactividad (TDAH). Los TS en población pediá trica tienen una prevalencia del 6-25%, mientras que en los niños con TND esta cifra asciende al 50-80%. En los TND se observa un incremento de las dificultades para conciliar el sueño, de los despertares nocturnos y de la somnolencia diurna. Así mismo, presentan alteracio nes del ritmo circadiano y trastornos respiratorios del sueño. Como consecuencia se produce una reducción de la alerta para las actividades diarias con incremento de trastornos conductuales, problemas emocionales y dificultades académicas asociadas a disfunciones eje cutivas y de memoria. La evaluación del sueño debe formar parte sistemática en la valoración clínica de los niños con TND, con el fin de realizar un diagnóstico y un tratamiento adecuados a cada caso, permitiendo mejorar la calidad de vida del niño y de su familia.

Abstract Sleep disorders are common in children and affect neurological development with important cognitive, emotional and behavioral repercussions. There is a high prevalence of sleep disorders (SD) in neurodevelop mental disorders (NDD) such as autism spectrum dis order (ASD) and attention-deficit hyperactivity disorder (ADHD). Sleep disorders in pediatric population have a prevalence of 6-25%, while in children with NDD this number rises to 50-80%. In NDDs, higher rates of dif ficulties in falling asleep, nocturnal awakenings and daytime sleepiness are observed. Disturbances in the circadian rhythm as well as respiratory sleep disorders are also observed. Consequently, there is a decrease in alertness for daytime activities with increased be havioral disorders, emotional problems and academic difficulties associated with executive and memory dys functions. Sleep assessment has to be a systemic part in the clinical evaluation of children with NDDs, so as to give a convenient diagnosis and treatment in each case, allowing to improve the quality of life of children and their families.

[Treatment of sleep disorders in neurodevelopmental disorders]. / Abordaje de los trastornos del sueño en los trastornos del neurodesarrollo.

Sleep disorders are common in children and affect neurological development with important cognitive, emotional and behavioral repercussions. There is a high prevalence of sleep disorders (SD) in neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Sleep disorders in pediatric population have a prevalence of 6-25%, while in children with NDD this number rises to 50-80%. In NDDs, higher rates of difficulties in falling asleep, nocturnal awakenings and daytime sleepiness are observed. Disturbances in the circadian rhythm as well as respiratory sleep disorders are also observed. Consequently, there is a decrease in alertness for daytime activities with increased behavioral disorders, emotional problems and academic difficulties associated with executive and memory dysfunctions. Sleep assessment has to be a systemic part in the clinical evaluation of children with NDDs, so as to give a convenient diagnosis and treatment in each case, allowing to improve the quality of life of children and their families.

Los trastornos del sueño son frecuentes en niños y afectan al desarrollo neurológico, con importante repercusión cognitiva, emocional y conductual. Existe una alta prevalencia de trastornos del sueño (TS) en los trastornos del neurodesarrollo (TND), como trastorno del espectro autista (TEA) y trastorno por déficit de atención con hiperactividad (TDAH). Los TS en población pediátrica tienen una prevalencia del 6-25%, mientras que en los niños con TND esta cifra asciende al 50-80%. En los TND se observa un incremento de las dificultades para conciliar el sueño, de los despertares nocturnos y de la somnolencia diurna. Así mismo, presentan alteraciones del ritmo circadiano y trastornos respiratorios del sueño. Como consecuencia se produce una reducción de la alerta para las actividades diarias con incremento de trastornos conductuales, problemas emocionales y dificultades académicas asociadas a disfunciones ejecutivas y de memoria. La evaluación del sueño debe formar parte sistemática en la valoración clínica de los niños con TND, con el fin de realizar un diagnóstico y un tratamiento adecuados a cada caso, permitiendo mejorar la calidad de vida del niño y de su familia.

Estudios neurofisiológicos en los trastornos del neurodesarrollo: potenciales evocados cognitivos / Neurophysiological studies in neurodevelopmental disorders: event related potentials

Resumen El trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno del espectro autista (TEA) son trastornos del neurodesarrollo cuyo diagnóstico es clínico y con gran variabilidad en la presentación clínica. La posibilidad de identificar y validar biomarcadores en estos trastornos del neurodesarrollo ayudaría no sólo en su diagnóstico sino también a la hora de implementar tratamientos personalizados y mo nitorizar la respuesta al tratamiento. Exploraciones neurofisiológicas como los potenciales evocados cognitivos (PEC), son una de las herramientas más utilizadas para evaluar de forma objetiva y con una alta resolución temporal las funciones cognitivas y proporcionan información sobre los mecanismos neurobiológicos subyacen tes, por lo que constituyen una herramienta de gran utilidad para valorar las alteraciones cognitivas asociadas a los trastornos del neurodesarrollo. Se han utilizado diferentes componentes de los PEC para el estudio de los trastornos del neurodesarrollo, como el componente P300, N400 o el componente N170 como biomarcador de la disfunción social en TEA. Revisamos los principales componentes de los PEC que se han estudiado como herramientas complementarias en el diagnóstico y en la monitorización de los tratamientos en los trastornos del neurodesarrollo.

Abstract Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevel opmental disorders whose diagnosis is clinical and with great variability in clinical presentation. The possibility of identifying and validating biomarkers in these neurodevelopmental disorders would help not only in their diagnosis, but also when implementing personalized treatments and monitori ng the response to treatment. Neurophysiologi cal examinations such as event related potentials (ERP) are one of the most widely used tools to objectively assess cognitive functions with high temporal resolution and provide information on the underlying neurobiological mechanisms, making them a very useful tool to assess cognitive alterations associated with neurodevelopmental disorders. Different components of the ERP have been used for the study of neurodevelopmental disorders, such as the P300, N400 component or the N170 component as a biomarker of social dysfunction in ASD. We review the main components of ERP that have been studied as complementary tools in the diagnosis and monitoring of treatments in neurodevelopmental disorders.

[Neurophysiological studies in neurodevelopmental disorders: event related potentials]. / Estudios neurofisiológicos en los trastornos del neurodesarrollo: potenciales evocados cognitivos.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders whose diagnosis is clinical and with great variability in clinical presentation. The possibility of identifying and validating biomarkers in these neurodevelopmental disorders would help not only in their diagnosis, but also when implementing personalized treatments and monitori ng the response to treatment. Neurophysiological examinations such as event related potentials (ERP) are one of the most widely used tools to objectively assess cognitive functions with high temporal resolution and provide information on the underlying neurobiological mechanisms, making them a very useful tool to assess cognitive alterations associated with neurodevelopmental disorders. Different components of the ERP have been used for t he study of neurodevelopmental disorders, such as the P300, N400 component or the N170 component as a biomarker of social dysfunction in ASD. We review the main components of ERP that have been studied as complementary tools in the diagnosis and monitoring of treatments in neurodevelopmental disorders.

El trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno del espectro autista (TEA) son trastornos del neurodesarrollo cuyo diagnóstico es clínico y con gran variabilidad en la presentación clínica. La posibilidad de identificar y validar biomarcadores en estos trastornos del neurodesarrollo ayudaría no sólo en su diagnóstico sino también a la hora de implementar tratamientos personalizados y monitorizar la respuesta al tratamiento. Exploraciones neurofisiológicas como los potenciales evocados cognitivos (PEC), son una de las herramientas más utilizadas para evaluar de forma objetiva y con una alta resolución temporal las funciones cognitivas y proporcionan información sobre los mecanismos neurobiológicos subyacentes, por lo que constituyen una herramienta de gran utilidad para valorar las alteraciones cognitivas asociadas a los trastornos del neurodesarrollo. Se han utilizado diferentes componentes de los PEC para el estudio de los trastornos del neurodesarrollo, como el componente P300, N400 o el componente N170 como biomarcador de la disfunción social en TEA. Revisamos los principales componentes de los PEC que se han estudiado como herramientas complementarias en el diagnóstico y en la monitorización de los tratamientos en los trastornos del neurodesarrollo.

Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma.

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

Detection of Helicobacter pylori Microevolution and Multiple Infection from Gastric Biopsies by Housekeeping Gene Amplicon Sequencing.

Despite the great efforts devoted to research on Helicobacter pylori, the prevalence of single-strain infection or H. pylori mixed infection and its implications in the mode of transmission of this bacterium are still controversial. In this study, we explored the usefulness of housekeeping gene amplicon sequencing in the detection of H. pylori microevolution and multiple infections. DNA was extracted from five gastric biopsies from four patients infected with distinct histopathological diagnoses. PCR amplification of six H. pylori-specific housekeeping genes was then assessed on each sample. Optimal results were obtained for the cgt and luxS genes, which were selected for amplicon sequencing. A total of 11,833 cgt and 403 luxS amplicon sequences were obtained, 2042 and 112 of which were unique sequences, respectively. All cgt and luxS sequences were clustered at 97% to 9 and 13 operational taxonomic units (OTUs), respectively. For each sample from a different patient, a single OTU comprised the majority of sequences in both genes, but more than one OTU was detected in all samples. These results suggest that multiple infections with a predominant strain together with other minority strains are the main way by which H. pylori colonizes the human stomach.

Marinobacter maroccanus sp. nov., a moderately halophilic bacterium isolated from a saline soil.

During the taxonomic investigation of exopolymer-producing halophilic bacteria, a rod-shaped, motile, Gram-stain-negative, halophilic bacterium, designated strain N4T, was isolated from a saline soil located in northern Morocco. Optimal growth of the isolate was at 30-37 ºC and at pH 7.0-8.0, in the presence of 5-7 % (w/v) NaCl. Useful characteristics for the phenotypic differentiation of strain N4T from other Marinobacter species included α-chymotrypsin and α-glucosidase activities and the carbohydrate assimilation profile. The major fatty acids detected in strain N4T were C16:0 and C18:1ω9c and the predominant respiratory quinone was ubiquinone-9. Sequence analysis of the 16S rRNA gene indicated that strain N4T belonged to the genus Marinobacter and was closely related to the type strains of Marinobacter adhaerens (99.04 % similarity), Marinobacter salsuginis (98.97 %) and Marinobacter flavimaris (98.36 %). Phylogenetic analysis of the rpoD gene sequence also showed that the nearest neighbours of strain N4T were M. salsuginis (91.49 % similarity), M. adhaerens and M. flavimaris (90.63 %). Strain N4T showed 87.98 % average nucleotide identity with M. flavimaris and M. salsuginis, and 87.47 % with M. adhaerens. Regarding in-silico genome-to-genome distance, strain N4T showed DNA-DNA hybridization values of 33.30 % with M. adhaerens, 34.60 % with M. flavimaris and 34.70 % with M. salsuginis. The DNA G+C content of strain N4T was 57.3 mol%. Based on the results of phenotypic characterization, phylogenetic analysis and genome comparison, strain N4T represents a novel species of the genus Marinobacter, for which the name Marinobacter maroccanus sp. nov. is proposed. The type strain is N4T (=CECT 9525T=LMG 30466T).

Gut microbiota dynamics and functionality in Reticulitermes grassei after a 7-day dietary shift and ciprofloxacin treatment.

Gut microbial structure in animals depends on the host, dietary habits and local environment. A random event, dietary change or antibiotic treatment may alter the gut environment with possible repercussions for the bacterial community composition and functionality and ultimately host fitness. The present study was focused on the composition, structure and functionality of gut microbiota in Reticulitermes grassei and the data obtained was compared with sequence surveys of three other Reticulitermes species. Each Reticulitermes species had a significantly different bacterial gut microbiota (pairwise significance tests using the Kolmogorov-Smirnov test), but a similar pattern of distribution (P-test in weighted Unifrac). The core gut microbiota from the analyzed Reticulitermes species contained 16 bacterial operational taxonomic units. Enzymes (KO) were detected from 14 pathways related to carbohydrate metabolism. R. grassei and R. hesperus, based on relative abundance of KO, had the most similar carbohydrate pathway patterns. In addition, we described the gut microbiota and functionality pathways in R. grassei after a 7-day dietary shift and antibiotic (ciprofloxacin) treatment. Both factors, but above all the antibiotic, altered the relative abundance of certain microbial groups, although the changes were not statistically significant (P-test in weighted Unifrac). The cellulose diet enhanced the carbohydrate pathways related to propanoate, butanoate, ascorbate, and glyoxylate metabolism. The antibiotic treatment affected galactose metabolism, the citrate cycle and inositol phosphate metabolism. Those functional changes may be related to changes in the abundance of several bacterial groups. Our findings provide insights into the stability of the gut microbiota in R. grassei and a resilience response to dietary shift or antibiotic treatment disturbance after 7 days.

Complete Genome Sequence of Marinobacter flavimaris LMG 23834T, Which Is Potentially Useful in Bioremediation.

The complete genome sequence of the halophilic strain Marinobacter flavimaris LMG 23834T is presented here. The genomic information of this type strain will be useful for taxonomic purposes and for its potential use in bioremediation studies.

Functional Stability and Community Dynamics during Spring and Autumn Seasons Over 3 Years in Camargue Microbial Mats.

Microbial mats are complex biofilms in which the major element cycles are represented at a millimeter scale. In this study, community variability within microbial mats from the Camargue wetlands (Rhone Delta, southern France) were analyzed over 3 years during two different seasons (spring and autumn) and at different layers of the mat (0-2, 2-4, and 4-6 mm). To assess bacterial diversity in the mats, amplicons of the V1-V2 region of the 16S rRNA gene were sequenced. The community's functionality was characterized using two approaches: (i) inferred functionality through 16S rRNA amplicons genes according to PICRUSt, and (ii) a shotgun metagenomic analysis. Based on the reads distinguished, microbial communities were dominated by Bacteria (∼94%), followed by Archaea (∼4%) and Eukarya (∼1%). The major phyla of Bacteria were Proteobacteria, Bacteroidetes, Spirochaetes, Actinobacteria, Firmicutes, and Cyanobacteria, which together represented 70-80% of the total population detected. The phylum Euryarchaeota represented ∼80% of the Archaea identified. These results showed that the total bacterial diversity from the Camargue microbial mats was not significantly affected by seasonal changes at the studied location; however, there were differences among layers, especially between the 0-2 mm layer and the other two layers. PICRUSt and shotgun metagenomic analyses revealed similar general biological processes in all samples analyzed, by season and depth, indicating that different layers were functionally stable, although some taxa changed during the spring and autumn seasons over the 3 years. Several gene families and pathways were tracked with the oxic-anoxic gradient of the layers. Genes directly involved in photosynthesis (KO, KEGG Orthology) were significantly more abundant in the top layer (0-2 mm) than in the lower layers (2-4 and 4-6 mm). In the anoxic layers, the presence of ferredoxins likely reflected the variation of redox reactions required for anaerobic respiration. Sulfatase genes had the highest relative abundance below 2 mm. Finally, chemotaxis signature genes peaked sharply at the oxic/photic and transitional oxic-anoxic boundary. This functional differentiation reflected the taxonomic diversity of the different layers of the mat.

Usefulness of Housekeeping Genes for the Diagnosis of Helicobacter pylori Infection, Strain Discrimination and Detection of Multiple Infection.

BACKGROUND: Helicobacter pylori infects human stomachs of over half the world's population, evades the immune response and establishes a chronic infection. Although most people remains asymptomatic, duodenal and gastric ulcers, MALT lymphoma and progression to gastric cancer could be developed. Several virulence factors such as flagella, lipopolysaccharide, adhesins and especially the vacuolating cytotoxin VacA and the oncoprotein CagA have been described for H. pylori. Despite the extensive published data on H. pylori, more research is needed to determine new virulence markers, the exact mode of transmission or the role of multiple infection. MATERIALS AND METHODS: Amplification and sequencing of six housekeeping genes (amiA, cgt, cpn60, cpn70, dnaJ, and luxS) related to H. pylori pathogenesis have been performed in order to evaluate their usefulness for the specific detection of H. pylori, the genetic discrimination at strain level and the detection of multiple infection. A total of 52 H. pylori clones, isolated from 14 gastric biopsies from 11 patients, were analyzed for this purpose. RESULTS: All genes were specifically amplified for H. pylori and all clones isolated from different patients were discriminated, with gene distances ranged from 0.9 to 7.8%. Although most clones isolated from the same patient showed identical gene sequences, an event of multiple infection was detected in all the genes and microevolution events were showed for amiA and cpn60 genes. CONCLUSIONS: These results suggested that housekeeping genes could be useful for H. pylori detection and to elucidate the mode of transmission and the relevance of the multiple infection.

Potential pathogenicity of Aeromonas hydrophila complex strains isolated from clinical, food, and environmental sources.

Aeromonas are autochthonous inhabitants of aquatic environments, including chlorinated and polluted waters, although they can also be isolated from a wide variety of environmental and clinical sources. They cause infections in vertebrates and invertebrates and are considered to be an emerging pathogen in humans, producing intestinal and extra-intestinal diseases. Most of the clinical isolates correspond to A. hydrophila, A. caviae, and A. veronii bv. Sobria, which are described as the causative agents of wound infections, septicaemia, and meningitis in immunocompromised people, and diarrhoea and dysenteric infections in the elderly and children. The pathogenic factors associated with Aeromonas are multifactorial and involve structural components, siderophores, quorum-sensing mechanisms, secretion systems, extracellular enzymes, and exotoxins. In this study, we analysed a representative number of clinical and environmental strains belonging to the A. hydrophila species complex to evaluate their potential pathogenicity. We thereby detected their enzymatic activities and antibiotic susceptibility pattern and the presence of virulence genes (aer, alt, ast, and ascV). The notably high prevalence of these virulence factors, even in environmental strains, indicated a potential pathogenic capacity. Additionally, we determined the adhesion capacity and cytopathic effects of this group of strains in Caco-2 cells. Most of the strains exhibited adherence and caused complete lysis.