Assessment of milk metabolites as biomarkers for predicting feed efficiency in dairy sheep.

Estimating feed efficiency (FE) in dairy sheep is challenging due to the high cost of systems that measure individual feed intake. Identifying proxies that can serve as effective predictors of FE could make it possible to introduce FE into breeding programs. Here, 39 Assaf ewes in first lactation were evaluated regarding their FE by 2 metrics, residual feed intake (RFI) and feed conversion ratio (FCR). The ewes were classified into high, medium and low groups for each metric. Milk samples of the 39 ewes were subjected to untargeted metabolomics analysis. The complete milk metabolomic signature was used to discriminate the FE groups using partial least squares discriminant analysis. A total of 41 and 26 features were selected as the most relevant features for the discrimination of RFI and FCR groups, respectively. The predictive ability when utilizing the complete milk metabolomic signature and the reduced data sets were investigated using 4 machine-learning algorithms and a multivariate regression method. The Orthogonal Partial Least Square algorithm outperformed other ML algorithms for the FCR prediction in the scenarios using the complete milk metabolite signature (r2 = 0.62 ± 0.06) and the 26 selected features (0.62 ± 0.15). Regarding RFI predictions, the scenarios using the 41 selected features outperformed the scenario with the complete milk metabolite signature, where the Multilayer feedforward artificial neural network (r2 = 0.18 ± 0.14) and extreme gradient boosting (r2 = 0.17 ± 0.15) outperformed other algorithms. The functionality of the selected metabolites implied that the metabolism of glucose, galactose, fructose, sphingolipids, amino acids, insulin, and thyroid hormones was at play. Compared with the use of traditional methods, practical applications of these biomarkers might simplify and reduce costs in selecting feed-efficient ewes.

Guidelines: basic principles of neurorehabilitation for patients with acquired brain injury. Recommendations of the Spanish Society of Neurorehabilitation.

INTRODUCTION: We present the Spanish Society of Neurorehabilitation's guidelines for adult acquired brain injury (ABI) rehabilitation. These recommendations are based on a review of international clinical practice guidelines published between 2013 and 2020. DEVELOPMENT: We establish recommendations based on the levels of evidence of the studies reviewed and expert consensus on population characteristics and the specific aspects of the intervention or procedure under research. CONCLUSIONS: All patients with ABI should receive neurorehabilitation therapy once they present a minimal level of clinical stability. Neurorehabilitation should offer as much treatment as possible in terms of frequency, duration, and intensity (at least 45-60minutes of each specific form of therapy that is needed). Neurorehabilitation requires a coordinated, multidisciplinary team with the knowledge, experience, and skills needed to work in collaboration both with patients and with their families. Inpatient rehabilitation interventions are recommended for patients with more severe deficits and those in the acute phase, with outpatient treatment to be offered as soon as the patient's clinical situation allows it, as long as intensity criteria can be maintained. The duration of treatment should be based on treatment response and the possibilities for further improvement, according to the best available evidence. At discharge, patients should be offered health promotion, physical activity, support, and follow-up services to ensure that the benefits achieved are maintained, to detect possible complications, and to assess possible changes in functional status that may lead the patient to need other treatment programmes.

Epigenetic regulation of functional candidate genes for milk production traits in dairy sheep subjected to protein restriction in the prepubertal stage.

BACKGROUND: As the prepubertal stage is a crucial point for the proper development of the mammary gland and milk production, this study aims to evaluate how protein restriction at this stage can affect methylation marks in milk somatic cells. Here, 28 Assaf ewes were subjected to 42.3% nutritional protein restriction (14 animals, NPR) or fed standard diets (14 animals, C) during the prepubertal stage. During the second lactation, the milk somatic cells of these ewes were sampled, and the extracted DNA was subjected to whole-genome bisulfite sequencing. RESULTS: A total of 1154 differentially methylated regions (DMRs) were identified between the NPR and C groups. Indeed, the results of functional enrichment analyses of the genes harboring these DMRs suggested their relevant effects on the development of the mammary gland and lipid metabolism in sheep. The additional analysis of the correlations of the mean methylation levels within these DMRs with fat, protein, and dry extract percentages in the milk and milk somatic cell counts suggested associations between several DMRs and milk production traits. However, there were no phenotypic differences in these traits between the NPR and C groups. CONCLUSION: In light of the above, the results obtained in the current study might suggest potential candidate genes for the regulation of milk production traits in the sheep mammary gland. Further studies focusing on elucidating the genetic mechanisms affected by the identified DMRs may help to better understand the biological mechanisms modified in the mammary gland of dairy sheep as a response to nutritional challenges and their potential effects on milk production.

Low-density SNP panel for efficient imputation and genomic selection of milk production and technological traits in dairy sheep.

The present study aimed to ascertain how different strategies for leveraging genomic information enhance the accuracy of estimated breeding values for milk and cheese-making traits and to evaluate the implementation of a low-density (LowD) SNP chip designed explicitly for that aim. Thus, milk samples from a total of 2,020 dairy ewes from 2 breeds (1,039 Spanish Assaf and 981 Churra) were collected and analyzed to determine 3 milk production and composition traits and 2 traits related to milk coagulation properties and cheese yield. The 2 studied populations were genotyped with a customized 50K Affymetrix SNP chip (Affymetrix Inc.) containing 55,627 SNP markers. The prediction accuracies were obtained using different multitrait methodologies, such as the BLUP model based on pedigree information, the genomic BLUP (GBLUP), and the BLUP at the SNP level (SNP-BLUP), which are based on genotypic data, and the single-step GBLUP (ssGBLUP), which combines both sources of information. All of these methods were analyzed by cross-validation, comparing predictions of the whole population with the test population sets. Additionally, we describe the design of a LowD SNP chip (3K) and its prediction accuracies through the different methods mentioned previously. Furthermore, the results obtained using the LowD SNP chip were compared with those based on the 50K SNP chip data sets. Finally, we conclude that implementing genomic selection through the ssGBLUP model in the current breeding programs would increase the accuracy of the estimated breeding values compared with the BLUP methodology in the Assaf (from 0.19 to 0.39) and Churra (from 0.27 to 0.44) dairy sheep populations. The LowD SNP chip is cost-effective and has proven to be an accurate tool for estimating genomic breeding values for milk and cheese-making traits, microsatellite imputation, and parentage verification. The results presented here suggest that the routine use of this LowD SNP chip could potentially increase the genetic gains of the breeding selection programs of the 2 Spanish dairy sheep breeds considered here.

Describing post-polio syndrome.

INTRODUCTION: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). OBJECTIVE: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. PATIENTS AND METHODS: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. RESULTS: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection > 2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. CONCLUSIONS: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.

Describiendo el síndrome pospolio / Describing post-polio syndrome

Introducción: Las personas con secuelas de poliomielitis pueden presentar nuevos síntomas que constituirían el síndrome pospolio (SPP). Objetivo Identificar el perfil clínico y funcional, y las características epidemiológicas de personas que padecen SPP. Pacientes y métodos: Estudio retrospectivo de 400 pacientes afectados de poliomielitis visitados en consulta externa del Institut Guttmann, de los cuales a 310 se les diagnosticó SPP. Se describieron variables epidemiológicas, clínicas y electromiográficas. Se analizó la relación entre edad de adquisición de la polio y gravedad de la misma, así como entre el sexo y la edad de aparición del SPP y la frecuencia de síntomas. Resultados: Se observó mayor frecuencia de SPP en mujeres (57,7%). La edad media de inicio de la clínica fue 52,4 años, más precoz en mujeres. Edad de primoinfección mayor de 2 años no se relacionó con mayor gravedad de la polio. La frecuencia de síntomas fue: dolor 85%, pérdida de fuerza 40%, fatiga 65,5%, cansancio 57,8%, intolerancia al frío 20,2%, disfagia 11,7%, quejas cognitivas 9%, síntomas depresivos 31,5%. La fatiga, el cansancio, la depresión y las quejas cognitivas fueron significativamente más frecuentes en mujeres. El 59% de los pacientes presentaban hallazgos electromiográficos sugestivos de SPP. Conclusiones: El tipo de sintomatología que presentaba nuestra muestra es similar a la publicada, no así en la frecuencia de la misma. Creemos que el perfil clínico de los pacientes podría ser muy diverso, y dar mayor peso a parámetros objetivos como el empeoramiento o la aparición de debilidad y el estudio de biomarcadores podría acercarnos más a un diagnóstico preciso. (AU)

Introduction: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). Objective: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. Patients and methods: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients’ epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. Results: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection > 2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. Conclusions: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients’ clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis. (AU)

Study on the concordance between different SNP-genotyping platforms in sheep.

Different SNP genotyping technologies are commonly used in multiple studies to perform QTL detection, genotype imputation, and genomic predictions. Therefore, genotyping errors cannot be ignored, as they can reduce the accuracy of different procedures applied in genomic selection, such as genomic imputation, genomic predictions, and false-positive results in genome-wide association studies. Currently, whole-genome resequencing (WGR) also offers the potential for variant calling analysis and high-throughput genotyping. WGR might overshadow array-based genotyping technologies due to the larger amount and precision of the genomic information provided; however, its comparatively higher price per individual still limits its use in larger populations. Thus, the objective of this work was to evaluate the accuracy of the two most popular SNP-chip technologies, namely, Affymetrix and Illumina, for high-throughput genotyping in sheep considering high-coverage WGR datasets as references. Analyses were performed using two reference sheep genome assemblies, the popular Oar_v3.1 reference genome and the latest available version Oar_rambouillet_v1.0. Our results demonstrate that the genotypes from both platforms are suggested to have high concordance rates with the genotypes determined from reference WGR datasets (96.59% and 99.51% for Affymetrix and Illumina technologies, respectively). The concordance results provided in the current study can pinpoint low reproducible markers across multiple platforms used for sheep genotyping data. Comparing results using two reference genome assemblies also informs how genome assembly quality can influence genotype concordance rates among different genotyping platforms. Moreover, we describe an efficient pipeline to test the reliability of markers included in sheep SNP-chip panels against WGR datasets available on public databases. This pipeline may be helpful for discarding low-reliability markers before exploiting genomic information for gene mapping analyses or genomic prediction.

Genome-wide association studies (GWAS) and post-GWAS analyses for technological traits in Assaf and Churra dairy breeds.

This study aimed to perform a GWAS to identify genomic regions associated with milk and cheese-making traits in Assaf and Churra dairy sheep breeds; second, it aimed to identify possible positional and functional candidate genes and their interactions through post-GWAS studies. For 2,020 dairy ewes from 2 breeds (1,039 Spanish Assaf and 981 Churra), milk samples were collected and analyzed to determine 6 milk production and composition traits and 6 traits related to milk coagulation properties and cheese yield. The genetic profiles of the ewes were obtained using a genotyping chip array that included 50,934 SNP markers. For both milk and cheese-making traits, separate single-breed GWAS were performed using GCTA software. The set of positional candidate genes identified via GWAS was subjected to guilt-by-association-based prioritization analysis with ToppGene software. Totals of 84 and 139 chromosome-wise significant associations for the 6 milk traits and the 6 cheese-making traits were identified in this study. No significant SNPs were found in common between the 2 studied breeds, possibly due to their genetic heterogeneity of the phenotypes under study. Additionally, 63 and 176 positional candidate genes were located in the genomic intervals defined as confidence regions in relation to the significant SNPs identified for the analyzed traits for Assaf and Churra breeds. After the functional prioritization analysis, 71 genes were identified as promising positional and functional candidate genes and proposed as targets of future research to identify putative causative variants in relation to the traits under examination. In addition, this multitrait study allowed us to identify variants that have a pleiotropic effect on both milk production and cheese-related traits. The incorporation of variants among the proposed functional and positional candidate genes into genomic selection strategies represent an interesting approach for achieving rapid genetic gains, specifically for those traits difficult to measure, such as cheese-making traits.

Estimation of genetic parameters for cheese-making traits in Spanish Churra sheep.

The global production of sheep milk is growing, and the main industrial use of sheep milk is cheese making. The Spanish Churra sheep breed is one of the most important native dairy breeds in Spain. The present study aimed to estimate genetic parameters for a wide range of traits influencing the cheese-making ability of Churra sheep milk. Using a total of 1,049 Churra ewes, we studied the following cheese-making traits: 4 traits related to milk coagulation properties (rennet coagulation time, curd-firming time, and curd firmness at 30 and 60 min after addition of rennet), 2 traits related to cheese yield (individual laboratory cheese yield and individual laboratory dried curd yield), and 3 traits measuring curd firmness over time (maximum curd firmness, time to attain maximum curd firmness, and syneresis). In addition, a list of milk traits, including the native pH of the milk and several milk production and composition traits (milk yield; the fat, protein, and dried extract percentages; and the somatic cell count), were also analyzed for the studied animals. After discarding the noncoagulating samples (only 3.7%), data of 1,010 ewes were analyzed with multiple-trait animal models by using the restricted maximum likelihood method to estimate (co)variance components, heritabilities, and genetic correlations. In general, the heritability estimates were low to moderate, ranging from 0.08 (for the individual laboratory dried curd yield trait) to 0.42 (for the fat percentage trait). High genetic correlations were found within pairs of related traits (i.e., 0.93 between fat and dried extract percentages, -0.93 between the log of the curd-firming time and curd firmness at 30 min, 0.70 between individual laboratory cheese yield and individual laboratory dried curd yield, and -0.94 between time to attain maximum curd firmness and syneresis). Considering all the information provided here, we suggest that in addition to the current consideration of the protein percentage trait for improving cheese yield traits, the inclusion of the pH of milk as a measured trait in the Churra dairy breeding program would represent an efficient strategy for improving the cheese-making ability of milk from this breed.

Describing post-polio syndrome. / Describiendo el síndrome pospolio.

INTRODUCTION: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). OBJECTIVE: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. PATIENTS AND METHODS: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. RESULTS: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection >2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. CONCLUSIONS: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.

Identification of a new Y chromosome haplogroup in Spanish native cattle.

The aim of this work was to perform a thorough analysis of the diversity of Y-haplotypes in Spanish cattle. A total of 207 Bos taurus males were sampled across 25 European breeds, with a special focus on rare, local Spanish populations. Animals were genotyped with five Y-specific microsatellites (INRA189, UMN0103, UMN0307, BM861 and BYM1), two indels (ZFY10 and USP9Y) and one SNP (UTY19). A new haplogroup, distinct from those described by Götherström et al. (2005), was identified and named Y1.2. Samples representing the three B. taurus Y-haplogroups were genotyped for four additional Y chromosome SNPs (rs121919254, rs121919281, rs121919323 and rs137049553). Among these SNPs, only rs121919281 was informative in B. taurus and helped to confirm the new Y1.2 haplogroup. Analysis of a larger dataset of standardized haplotypes for 1507 individuals from 57 populations from Spain, other European countries and Africa showed the new Y1.2 haplogroup to be found exclusively in Spanish breeds. This finding reinforces the importance of local Spanish cattle as reservoirs of genetic diversity as well as the importance of the Iberian Peninsula in the history of cattle.

Correlation of higher order aberrations in the anterior corneal surface and degree of keratoconus measured with a Scheimpflug camera. / Correlación de aberraciones de alto orden en la cara anterior de la córnea y el grado de queratocono medidas con cámara de Scheimpflug.

OBJECTIVE: To determine the correlation of higher order aberrations in anterior corneal surface and degree of keratoconus measured with a Scheimpflug camera. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted on 152 eyes (both eyes of each patient) of patients with keratoconus, from January 2009 to April 2014. An examination was performed on the corneal aberrometry in the anterior corneal surface, and topographic mapping (by Amsler and Muckenhirn classification) was used to determine the degree of keratoconus. The correlation between high-order aberrations in anterior corneal surface and the degree of keratoconus was determined. RESULTS: Coma aberration significantly correlated with keratoconus severity (r=.60, P<.01), as well as with the high order aberration (r=.61, P<.01). Trefoil and keratoconus were weakly correlated (r=.34, P<.01). CONCLUSION: Higher order aberrations in anterior corneal surface were positively correlated with the degree of keratoconus in a similar way to the entire optical system.

Behavioural linear standardized scoring system of the Lidia cattle breed by testing in herd: estimation of genetic parameters.

Docility is very important for cattle production, and many behavioural tests to measure this trait have been developed. However, very few objective behavioural tests to measure the opposite approach 'aggressive behaviour' have been described. Therefore, the aim of this work was to validate in the Lidia cattle breed a behavioural linear standardized scoring system that measure the aggressiveness and enable genetic analysis of behavioural traits expressing fearless and fighting ability. Reproducibility and repeatability measures were calculated for the 12 linear traits of this scoring system to assess its accuracy, and ranged from 85.3 and 94.2%, and from 66.7 to 97.9%, respectively. Genetic parameters were estimated using an animal model with a Bayesian approach. A total of 1202 behavioural records were used. The pedigree matrix contained 5001 individuals. Heritability values (with standard deviations) ranged between 0.13 (0.04) (Falls of the bull) and 0.41 (0.08) (Speed of approach to horse). Genetic correlations varied from 0.01 (0.07) to 0.90 (0.13). Finally, an exploratory factor analysis using the genetic correlation matrix was calculated. Three main factors were retained to describe the traditional genetic indexes aggressiveness, strength and mobility.

Contribution of Lidia cattle breed historical castes to the paternal genetic stock of Spain.

The main objective of this work was to determine whether the five founding castes defined in the Lidia cattle breed actually have an important contribution to the Spanish paternal genetic stock as well as to the paternal genetic origin support. A total of 1300 Bos taurus male individuals were genotyped for five microsatellites (INRA189, UMN0103, UMN0307, BM861 and BYM1) and one indel (ZFY10). Microsatellite and indel alleles were combined into haplotypes, identifying a total of 38 haplotypes, 11 of them belonging to haplogroup Y1 and 27 to haplogroup Y2. Ten different haplotypes were found in the Lidia cattle breed, with five being exclusive to this breed. Our results agree with different male genetic stocks in the Lidia breed: one hypothetically representing the ancient Iberian bovine genetic stock (Gallardo, Navarra and Cabrera castes and some encastes from Vistahermosa) and a second one that is the result of the more recent breeding strategy of choosing the most aggressive individuals from traditional herds (including some Vistahermosa encastes and the Vazqueña caste). In terms of conservation, it would be better to not consider this breed as a unit but to consider the caste, or even better the encaste, as the target of putative conservation efforts.

Referred sensations and neuropathic pain following spinal cord injury.

It has been proposed that painful and non-painful referred sensations (RSs) are associated with reorganization of sensory pathways in patients with complete spinal cord injury (SCI). In order to investigate the referred sensation (RS) phenomenon and its correlation with neuropathic pain (NP) 48 patients with complete SCI, 24 with chronic NP and 24 without pain or paraesthesias were studied using clinical examination and neurophysiological tests. Patients reporting RSs were re-examined at 2 and 10weeks after the first examination. We defined the presence of RS as sensations perceived below the injury level in response to touch and pinprick stimuli in various body points above the injury level. The examination was carried out by one researcher applying the stimuli to the patient under two visual conditions (open and closed eyes), and then asking the patient to make tactile self-stimulation. Seven patients with SCI and NP (29%) reported RS below the injury level. RS were well located and consistently evoked at repeated examinations. Touch and pinprick stimulation elicited similar RS that were non-painful in six patients and painful in one. Visual feedback did not change RS perception and characteristics. None of the patients in the SCI group without NP presented RS. In conclusion, our results indicate that RS is relatively frequent in patients with complete SCI and NP. The common occurrence of RS in patients with NP and the location of the sensations in the same area as NP suggest that pain and RS share common pathophysiological mechanisms.

Do multimodal evoked potentials add information to MRI in clinically isolated syndromes?

The role of multimodal evoked potentials (MMEPs) in establishing multiple sclerosis (MS) diagnosis and prognosis has diminished nowadays. The objective of this article is to evaluate whether MMEPs add information to MRI in identifying patients with higher risk of relapse or development of disability after a clinically isolated syndrome (CIS). Patients who underwent visual, somato-sensory and brainstem auditory evoked potentials (EPs) were identified from a cohort of consecutive CIS. Patients also underwent brain MRI within 3 months of first attack. We analysed time to second attack and to Expanded Disability Status Scale (EDSS) score of 3.0 according to number of Barkhof criteria and number of abnormal MMEPs. A complete study was performed in 245 patients who were followed for a mean of 76.4 months (interquartile range: 61 to 96). Seventy-one patients (29%) had the three EPs normal, 115 patients (47%) had one abnormal EP; 40 patients (16%) had two; and 19 patients (8%) had three abnormal EPs. Baseline MRI determined the risk for converting to clinically definite MS and correlated with disability according to previous studies. EPs individually did not modify the risk of conversion or disability. However, the presence of three abnormal EPs increased the risk of reaching moderate disability (hazard ratio 7.0; 1.4-34.9) independently of baseline MRI. In conclusion, in the presence of three abnormal EPs could help identify CIS patients with a higher risk of developing disability, independently of MRI findings. However, the utility of MMEPs is limited by the low percentage of CIS patients having the three abnormal at baseline.

Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis?

BACKGROUND: To evaluate whether oligoclonal bands (OB) add information to MRI in predicting both a second attack and development of disability in patients with clinically isolated syndromes (CIS). METHODS: From 1995 to 2006, 572 patients with CIS were included in a prospective study. Patients underwent brain MRI and determination of OB within 3 months of first attack. The number and location of lesions and presence of OB were studied. We analyzed time to second attack and to Expanded Disability Status Scale 3.0 according to number of Barkhof criteria (BC) and the presence or absence of OB. RESULTS: We studied 415 (73%) patients with CIS with both baseline MRI and determination of OB. Patients were followed for a mean of 50 months (SD 31). Compared to the reference group with 0 BC at baseline MRI, patients with one to two BC showed a hazard ratio (HR) for conversion to CDMS of 3.8 (2.0 to 7.2) and patients with three to four BC of 8.9 (4.8 to 16.4). Of the total cohort, OB were positive in 61% of the patients. However, broken down by MRI group, OB were positive in 31% of those with no BC; 69% of those with one to two BC; and 85% of those with three or four BC. The presence of OB increased the risk of a second relapse (HR 1.7; 1.1 to -2.7) independently of baseline MRI but did not modify the development of disability. CONCLUSIONS: Presence of oligoclonal bands doubles the risk for having a second attack, independently of MRI, but does not seem to influence the development of disability.

Linfopoyesis temprana en médula ósea adulta / Early lymphopoiesis in adult bone marrow

El desarrollo de las células linfoides a partir de células troncaleshematopoyéticas es un proceso organizado en el que se pierdengradualmente múltiples potenciales de diferenciación alternos;y coinciden el compromiso de linaje y la ganancia de funcionesespecializadas. En los últimos años se han registrado avancesnotables en la caracterización de los progenitores primitivosque dan inicio al programa linfoide, y en la definición de los patronesde actividad transcripcional que controlan las decisiones dellinaje, aunque está poco definida la relación entre las señalesambientales y la estabilidad de la ruta de diferenciación linfoide.Esta revisión bibliográfica pretende proporcionar un panoramaclaro del conocimiento actual en los eventos tempranos de la linfopoyesisy su interrelación con el microambiente hematopoyético

Development of lymphoid cells from hematopoietic stem cellsis an ordered process where multiple alternate lineage potentialsare gradually lost and lineage commitment is coincident with gainof specialized functions. Over the last few years remarkableadvances have been made in characterizing primitive progenitorsthat initiate the lymphoid program, and patterns of transcriptionalactivity controlling lineage fate decisions during normalhematopoiesis, but less is known about environmental signalsthat may influence the differentiation pathway stability. Thisreview discusses the current knowledge with relevance to hierarchyand early events in lymphopoiesis and their relationship tohematopoietic microenvironment

Polyregional and hemispheric syndromes: a study of these uncommon first attacks in a CIS cohort.

Clinically isolated syndromes (CIS) classically refer to optic neuritis (ON), brainstem or spinal cord syndromes. Less common first episodes suggestive of central nervous system (CNS) demyelination, such as hemispheric or clinically polyregional syndromes, have been only slightly studied. The aim of this study was to describe these CIS topographies in our cohort of patient with a CIS. We evaluated 320 patients with a CIS, and classified the topographies of the attacks according to clinical symptoms only into CIS of the optic nerve (123), brainstem (78), spinal cord (89), hemispheric (6), polyregional (12) or undetermined (12) topographies. Patients underwent brain MRI within three months of their first attack, and again 12 months later. Conversion to multiple sclerosis (MS), determined either clinically or by magnetic resonance imaging (MRI), was evaluated according to topography. Hemispheric and polyregional syndromes were closer to brainstem or spinal cord syndromes than ON in clinical and MRI conversion terms, although a statistical analysis was not performed because of the small number of patients. There are differences between several studies in the definition, and, therefore, the prevalence of these so-called atypical CIS. Consensus on the denomination and definition of these syndromes must be reached.

Baseline MRI predicts future attacks and disability in clinically isolated syndromes.

OBJECTIVE: To determine the relation between baseline MRI and both conversion to multiple sclerosis (MS) and development of disability in a cohort of patients with clinically isolated syndromes (CIS). METHODS: From 1995 to 1998, 175 consecutive patients with CIS underwent brain MRI within 3 months of their first attack and again 12 months and 5 years later. We studied the number and location of lesions at baseline and development of new T2 lesions. We also analyzed conversion to MS and development of disability (Expanded Disability Status Scale [EDSS] > or = 3.0). RESULTS: We included 156 patients with CIS followed for a median of 7 years. Compared to the reference group with 0 Barkhof criteria at baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low, medium, and high conversion risk. EDSS at year 5 correlated with baseline number of Barkhof criteria (r = 0.46, p < 0.0001). When categorizing by number of baseline lesions, similar results were seen. Patients with a baseline MRI with three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for reaching EDSS > or = 3.0. Only 10% of the latter had disability at year 5, but 40% reached this at 8 years. CONCLUSIONS: Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.