The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Associació entre la bateria cognitiva neuronorma i els biomarcadors de líquid cefaloraquidi en el contínuum de la malaltia d'Alzheimer

La malaltia d'Alzheimer (MA) es caracteritza per un deteriorament cognitiu de tipus progressiu. Les valoracions neuropsicològiques són fonamentals per a definir el perfil d'afectació i contribuir al diagnòstic. D'altra banda, en les últimes dècades l'avenç en el coneixement sobre el procès fisiopatològic de la malaltia i el progrés en noves tècniques diagnòstiques han permès definir uns biomarcadors els quals han contribuït a conceptualitzar la MA com un contínuum biològic el qual abasta diferents fases clíniques (des de la cognició normal fins a la demència). Els objectius d'aquesta tesi són, per un costat, mostrar l'associació entre les diferents variables cognitives d'una bateria estandarditzada, la bateria Neuronorma, amb les diferents mesures de líquid cefalorraquidi (LCR) considerades com a biomarcadors de la MA en subjectes cognitivament sans (CS), amb deteriorament cognitiu lleu (DCLL) i amb demència tipus Alzheimer (DTA) en fase lleu. A més a més, s'estudien les distàncies relatives tant de les variables cognitives com biològiques per a determinar la seva capacitat de discriminació entre aquests grups clínics. Per altre costat, en aquest treball també es comparen els perfils cognitius entre diferents grups de subjectes classificats segons les variants A/T/N proposades actualment per la National Institute on Aging and Alzheimer's disease Association (NIA-AA) com a esquema de classificació en l'àmbit de recerca. La mostra es compon per un total de 112 subjectes (42 CS, 35 DCLL i 35 DTA lleu) els quals van ser explorats cognitivament amb la bateria Neuronorma que integra un conjunt de tests neuropsicològics que evaluen diferents dominis cognitius. Es van obtenir mostres de LCR de cadascun dels subjectes mitjançant una punció lumbar (PL) i es van analitzar les següents mesures: la proteïna beta-amiloide (βA), específicament la βA1-42, i la proteïna Tau total (t-tau) i tau fosforilada (p-tau). Es van calcular coeficients de correlació per a analitzar l'associació entre les diferents variables cognitives i les mesures de LCR en la mostra global. Es va realitzar una anàlisi multivariant i un posterior estudi de magnitud de l'efecte per a la comparació i discriminació entre els grups de subjectes. En darrer lloc, es van transformar les puntuacions brutes dels tests a puntuacions escalars (corregides per edat i escolaritat segons els barems Neuronorma) i posteriorment es va calcular la mediana d'aquestes últimes per a construir els perfils cognitius. A mode general, les conclusions d'aquest estudi són: en primer lloc, existeix una associació entre les variables cognitives estudiades i les diferents mesures de biomarcadors de LCR de la MA. A més a més, s'evidencia una major alteració cognitiva i en les mesures biològiques com més greu sigui el diagnòstic clínic (en aquesta ocasió, es comparen els grups diagnòstics de CS, DCLL i DTA lleu). D'altra banda, es mostra que les variables de l'àmbit cognitiu de memòria i algunes de funcions executives (FFEE) són les que millor discriminen entre CS i els grups que presenten deteriorament. I, per últim, s'observa que els subjectes que presenten positivitat en aquests biomarcadors tendeixen a obtenir rendiments cognitius més baixos respecte a aquells subjectes que presenten biomarcadors normals.La enfermedad de Alzheimer (EA) se caracteriza por un deterioro cognitivo de tipo progresivo. Las valoraciones neuropsicológicas son fundamentales para definir el perfil de afectación y contribuir al diagnóstico. Por otra parte, en las últimas décadas el avance en el conocimiento sobre el proceso fisiopatológico de la enfermedad y el progreso en nuevas técnicas de diagnóstico han permitido definir varios biomarcadores; estos han contribuido a conceptualizar la EA como un continuo biológico que comprende distintas fases clínicas (desde la cognición normal hasta la demencia). Los objetivos de esta tesis son, por un lado, mostrar la asociación entre las distintas variables cognitivas de una batería estandarizada (la batería Neuronorma), con las diferentes medidas de líquido cefalorraquídeo (LCR), consideradas como biomarcadores de la EA, en sujetos cognitivamente sanos (CS), con deterioro cognitivo leve (DCL) y con demencia tipo Alzheimer (DTA) en fase leve. Además, se estudian las distancias relativas tanto de las variables cognitivas como biológicas, a fin de determinar su capacidad de discriminación entre estos grupos clínicos. Por otra parte, en este trabajo también se comparan los perfiles cognitivos entre diferentes grupos de sujetos clasificados según las variantes A/T/N propuestas actualmente por la National Institute on Aging and Alzheimer's disease Association (NIA-AA) como esquema de clasificación en el ámbito de la investigación. La muestra se compone de un total de 112 sujetos (42 CS, 35 DCLL y 35 DTA leve) los cuales fueron explorados cognitivamente con la batería Neuronorma, que integra un conjunto de tests neuropsicológicos que evalúan diferentes dominios cognitivos. Se obtuvieron muestras de LCR de cada uno de los sujetos mediante una punción lumbar (PL) y se analizaron las siguientes medidas: la proteína beta-amiloide (βA), específicamente la βA1-42, i la proteína Tau total (t-tau) y tau fosforilada (p-tau). Se calcularon coeficientes de correlación para analizar la asociación entre las diferentes variables cognitivas y las medidas de LCR en la muestra global. Se realizó un análisis multivariante y un posterior estudio de magnitud del efecto para la comparación y discriminación entre los grupos de sujetos. Por último, se transformaron las puntuaciones brutas de los tests a puntuaciones escalares (corregidas por edad y escolaridad según los baremos Neuronorma) y posteriormente se calculó la mediana de éstas últimas para construir los perfiles cognitivos. A modo general, las conclusiones de este estudio son: en primer lugar, que existe una asociación entre las variables cognitivas estudiadas y las diferentes medidas de biomarcadores de LCR de la EA. Además, se evidencia una mayor alteración cognitiva y en las medidas biológicas cuanto más grave sea el diagnóstico clínico (en esta ocasión, se comparan los grupos diagnósticos de CS, DCL y DTA leve). Por otra parte, se muestra que las variables del ámbito cognitivo de memoria y algunas de funciones ejecutivas (FFEE) son las que mejor discriminan entre CS y los grupos que presentan deterioro. Y, por último, se observa que los sujetos que presentan positividad en estos biomarcadores tienden a obtener rendimientos cognitivos más bajos respecto aquellos sujetos que presentan biomarcadores normales.Alzheimer's disease (AD) is characterized by progressive cognitive impairment. Neuropsychological assessments are essential to define the profile of those cognitive changes and to contribute to their diagnosis. The last decades have seen major advances in our understanding of the physio-pathological processes of the disease. Combining said advances with the newer diagnostic techniques, we are now able to define certain biomarkers which have contributed to the conceptualization of AD as a biological continuum, covering different clinical phases (from normal cognition to dementia). The objectives of this thesis are twofold: Firstly, we show the association between the cognitive variables of a standardized battery (the Neuronorma battery) and the measurements of cerebrospinal fluid (CSF), since those are considered AD biomarkers, in cognitively healthy controls (HC) as well as in subjects with mild cognitive impairments (MCI) and mild AD. Additionally, the relative distances of both cognitive and biological variables are studied to determine their capacity of discrimination between these clinical groups. Secondly, this project also compares the cognitive profiles of different groups of subjects, classified according to the A/T/N variants currently proposed by the National Institute on Aging and Alzheimer's disease Association (NIA-AA) as a classification scheme in the research field. The sample is composed of 112 subjects (42 HC, 35 with MCI and 35 with mild AD), cognitively explored using the Neuronorma battery that integrates a set of neuropsychological tests that assesses different cognitive domains. CSF samples were obtained from each subject via a lumbar puncture (LP) and the following values were analyzed: beta-amyloid protein (βA), specifically βA1-42, as well as total Tau proteins (t-tau) and phosphorylated tau (p-tau). Correlation coefficients were calculated to analyze the association between different cognitive variables and CSF measurements in the global sample. A multivariate analysis and a subsequent effect size study were carried out in order to compare and distinguish between the groups of subjects. Finally, the test raw scores were transformed into scalar scores (corrected by age and schooling, according to the Neuronorma scales) and the median of these scores was calculated to construct the cognitive profiles. In general, the conclusions of this study are: firstly, there is an association between the analyzed cognitive variables and the different measurements of CSF biomarkers of AD. Secondly, the greater the cognitive and biological alteration, the more severe the clinical diagnosis (in this occasion, the diagnostic groups of HC, MCI and mild AD are compared). On the other hand, it becomes apparent that memory and executive function (EEFF) are the variables that discriminate better between HC and the groups with cognitive impairments. Finally, it is observed that subjects which test positive for these biomarkers tend to show lower cognitive performances, compared to subjects showing normal biomarkers

Factors associated to neurocognitive impairment in older adults living with HIV

Objective: The HIV infection is a chronic disease that causes neurocognitive impairment (NI) and has been related with early development of frailty. We aimed to study the main risk factors for neurocognitive disorders and frailty in HIV older adults. Materials and methods: Cross-sectional study with 40 HIV individuals older than 65 years under antiretroviral therapy in Hospital del Mar (Barcelona) recruited between November 2019 and October 2020. Data has been obtained through clinical scores and a blood sample to evaluate NI and frailty and has been analyzed with non-parametric tests and a multivariate logistic regression model. Results: Among the 40 patients admitted for the study, 14 (35%) had positive screening for NI. We found that HIV individuals with nadir CD4+ T-cell count lower than 350 cells/mm3 had 39.7 more risk for NI (95% CI 2.49-632.10; p = 0.009). Those with a lower education level had 22.78 more risk for neurocognitive disorders (95% CI 2.13-242.71; p = 0.01) and suffering any comorbidity with a punctuation ≥ 1 in the Charlson Comorbidity index had an increased risk of 18.26 of developing NI and frailty (95% CI 1.30-256.33; p = 0.031), among them diabetes was significantly more frequent in NI. Conclusion: We observed that the main risk factors for a positive NI screening in HIV older adults were low education level, a nadir CD4+ T-cell count < 350 cells/mm3 and the presence of any comorbidity, highlighting diabetes among them

Development, equivalence study, and normative data of version B of the Spanish-language Free and Cued Selective Reminding Test

Introduction: The Free and Cued Selective Reminding Test (FCSRT) is widely used for the assessment of verbal episodic memory, mainly in patients with Alzheimer disease. A Spanish-language version of the FCSRT and normative data were developed within the NEURONORMA project. Availability of alternative, equivalent versions is useful for following patients up in clinical settings. This study aimed to develop an alternative version of the original FCSRT (version B) and to study its equivalence to the original Spanish-language test (version A), and its performance in a sample of healthy individuals, in order to develop reference data. Methods: We evaluated 232 healthy participants of the NEURONORMA-Plus project, aged between 18 and 90. Thirty-three participants were assessed with both test versions using a counterbalanced design. Results: High intra-class correlation coefficients (between 0.8 and 0.9) were observed in the equivalence study. While no significant differences in performance were observed in total recall scores, free recall scores were significantly lower for version B. Conclusions: These preliminary results suggest that the newly developed FCSRT version B is equivalent to version A in the main variables tested. Further studies are necessary to ensure interchangeability between versions. We provide normative data for the new version

Desarrollo, estudio de equivalencia y datos normativos de la versión española B del Free and Cued Selective Reminding Test

INTRODUCTION: The Free and Cued Selective Reminding Test (FCSRT) is widely used for the assessment of verbal episodic memory, mainly in patients with Alzheimer disease. A Spanish version of the FCSRT and normative data were developed within the NEURONORMA project. Availability of alternative, equivalent versions is useful for following patients up in clinical settings. This study aimed to develop an alternative version of the original FCSRT (version B) and to study its equivalence to the original Spanish test (version A), and its performance in a sample of healthy individuals, in order to develop reference data. METHODS: We evaluated 232 healthy participants of the NEURONORMA-Plus project, aged between 18 and 90. Thirty-three participants were assessed with both versions using a counterbalanced design. RESULTS: High intra-class correlation coefficients (between 0.8 and 0.9) were observed in the equivalence study. While no significant differences in performance were observed in total recall scores, free recall scores were significantly lower for version B. CONCLUSIONS: These preliminary results suggest that the newly developed FCSRT version B is equivalent to version A in the main variables tested. Further studies are necessary to ensure interchangeability between versions. We provide normative data for the new version

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task

Data de publicació electrónica: 14-09-2021Introducción: las tareas de atención compleja y fluencia no verbal se utilizan en las valoraciones neuropsicológicas con el objetivo de explorar subdominios de las funciones ejecutivas. El objetivo de este estudio es proporcionar datos normativos ajustados por edad, escolaridad y género de las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT) como parte del Proyecto NEURONORMA-Plus. Método: se incluyeron 308 individuos sin deterioro cognitivo de entre 18 y 92 años de edad. Se convirtieron las puntuaciones brutas en puntuaciones escalares ajustadas por edad y se realizaron ajustes por escolaridad y género aplicando regresiones lineales estratificando en dos grupos de edad (< 50 y ≥ 50 años). Resultados: globalmente la edad tuvo un impacto negativo en el DK-DFT y el CTT. La escolaridad mostró un efecto positivo en las puntuaciones del DK-DFT sólo en el grupo de mayor edad (≥ 50 años) y se halló un rendimiento discretamente superior en los hombres más jóvenes en la condición básica de esta prueba. La escolaridad se asoció positivamente con todas las puntuaciones de CTT en ambos grupos de edad, excepto en la subprueba CTT-1 en el grupo de adultos jóvenes. La edad y la escolaridad no mostraron influencia sobre el rendimiento en el DT, a diferencia del género, ya que las mujeres jóvenes tuvieron un rendimiento ligeramente superior. Conclusión: estos datos normativos pueden resultar útiles para la interpretación de las evaluaciones neuropsicológicas en población española

Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task

Article disponible en castellà: http://hdl.handle.net/10230/53668Introduction: Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. Methods: The sample included 308 cognitively unimpaired individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). Results: Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. Conclusions: These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population

Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test

Data de publicació electrónica: 20-09-2021Objetivo: ell presente estudio tiene como objetivo proporcionar normas y ajustes para edad, educación y género para el Wisconsin Card Sorting Test (WCST), la Figura Compleja Modificada de Taylor (FCMT) y el Ruff-Light Trail Learning Test (RULIT) como parte del proyecto NEURONORMA-Plus. método: la muestra consiste en 308 individuos cognitivamente sanos de entre 18 y 92 años. Se proporcionan tablas para convertir las puntuaciones brutas en puntuaciones escalares ajustadas por edad y ajustes por educación y género tras aplicar modelos de regresión independientes en 2 grupos de edad (< 50 y ≥ 50 años).Resultados: la edad tuvo un efecto negativo en el rendimiento en ambos grupos etarios. Observamos un efecto positivo de la educación en el rendimiento del WCST en el grupo más joven (< 50 años), y en todas las medidas del FCMT (con la excepción de la tarea de reconocimiento) en el grupo de mayor edad (≥ 50 años). La educación no influyó en el rendimiento en el RULIT, pero sí el género, que tuvo un efecto leve, aunque significativo, mostrando los hombres jóvenes un mayor rendimiento en una variable. conclusión: los datos normativos aportados pueden contribuir en la interpretación clínica del rendimiento en estas pruebas en población española

Spanish normative studies (NEURONORMA-Plus project): norms for the Wisconsin Card Sorting Test, the Modified Taylor Complex Figure, and the Ruff-Light Trail Learning Test

Article disponible en castellà: http://hdl.handle.net/10230/53669Objective: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project. Methods: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years). Results: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (< 50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥ 50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable. Conclusion: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population