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Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional “first-line” and “second-line” treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS.

BackgroundAlthough fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders.ObjectiveThe main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up.MethodsA retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed.ResultsA total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies >24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0).ConclusionMS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.

BackgroundLimited information is available on the active process of seeking medical help in patients with Alzheimer’s disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors.MethodsA multicenter, non-interventional study was conducted including patients of 50–90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer’s Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5–1.0. A multivariate logistic regression analysis was conducted.ResultsA total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016).ConclusionUnderstanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition.

BackgroundEpstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler’s murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo. Furthermore, teriflunomide inhibits lytic EBV infection in vitro.Objective1. To evaluate the humoral response against EBV and HHV-6 prior to teriflunomide treatment and 6 months later. 2. To correlate the variation in the humoral response against EBV and HHV-6 with the clinical and radiological response after 24 months of treatment with teriflunomide. 3. To analyze the utility of different demographic, clinical, radiological, and environmental data to identify early biomarkers of response to teriflunomide.MethodsA total of 101 MS patients (62 women; mean age: 43.4 years) with one serum prior to teriflunomide onset and another serum sample 6 months later were recruited. A total of 80 had been treated for at least 24 months, 13 had stopped teriflunomide before 24 months, and 8 were currently under teriflunomide therapy but with less than 24 months of follow-up. We analyzed the levels of the viral antibodies titers abovementioned in serum samples with ELISA commercial kits, and the levels of serum neurofilament light chain (Nf-L).ResultsAntiviral antibody titers decreased for EBNA-1 IgG (74.3%), VCA IgG (69%), HHV-6 IgG (60.4%), and HHV-6 IgM (73.3%) after 6 months of teriflunomide. VCA IgG titers at baseline correlated with Nf-L levels measured at the same time (r = 0.221; p = 0.028) and 6 months later (r = 0.240; p = 0.017). We found that higher EBNA-1 titers (p = 0.001) and a higher age (p = 0.04) at baseline were associated with NEDA-3 conditions. Thus, 77.8% of patients with EBNA-1 >23.0 AU and >42.8 years (P50 values) were NEDA-3.ConclusionTreatment with teriflunomide was associated with a reduction of the levels of IgG antibody titers against EBV and HHV-6. Furthermore, higher EBNA-1 IgG titers prior to teriflunomide initiation were associated with a better clinical response.

Abstract We developed an ELISA assay demonstrating the high prevalence of serum IgM to phosphatidylcholine (IgM-PC) in the first stages of multiple sclerosis (MS). We aimed to analyze the role of serum IgM-PC as a biomarker of response to treatment. Paired serum samples from 95 MS patients were obtained before (b.t) and after (a.t) treatment with disease modifying therapies. Patients were classified as non-responders or responders to treatment, according to classical criteria. Serum IgM-PC concentration was analyzed using our house ELISA assay. The level of serum IgM-PC b.t was higher in patients treated later with natalizumab than in those treated with Copaxone (p = 0.011) or interferon-β (p = 0.009). Responders to natalizumab showed higher concentration of serum IgM-PC b.t than those who did not respond to it (p = 0.019). The 73.3% of patients with the highest level of serum IgM-PC b.t responded to natalizumab. IgM-PC level decreased a.t in both cases, non-responders and responders to natalizumab. IgM-PC levels a.t did not decrease in non-responders to interferon-β, but in responders to it the IgM-PC level decreased (p = 0.007). Serum IgM-PC could be a biomarker of response to natalizumab or interferon-β treatment. Further studies would be necessary to validate these results.

Abstract The detection of intrathecal IgA synthesis (IAS) in multiple sclerosis (MS) could be underestimated. To assess it, we develop a highly sensitive assay based on isoelectric focusing (IEF). 151 MS patients and 53 controls with different neurological diseases were recruited. IgA concentration was analyzed using a newly developed in house ELISA. IgA oligoclonal bands to detect IAS were determined by IEF. Most individuals showed an IgA concentration within normal range in serum samples (90.69%) but 31.37% of individuals had a IgA concentration below the normal range in the cerebrospinal fluid (CSF). No significant differences were observed between MS and control groups, neither in CSF nor in serum. The new IEF was more sensitive than those previously described (0.01 mg/dl of IgA), and clearly identified patients with and without IAS, that was not related with IgA concentration. Using IEF, MS patients showed higher percentage of IAS-IEF (43.00%) than the control group (16.98) (p = 0.001). The incidence was especially higher in patients with clinically isolated syndrome (66.00%). The new IFE demonstrated a higher percentage of IAS in MS patients than assumed in the past. The presence of IAS-IEF in MS is higher than in other neurological diseases.

Objectives1. To analyze the prevalence and levels of anti-EBNA-1 and anti-VCA IgG antibodies of Epstein-Barr virus (EBV) in a Spanish cohort of multiple sclerosis (MS) patients and their interactions with other environmental and genetic risk factors. 2. To analyze the association of the evolution of these antibodies with the clinical response to different disease modifying therapies (DMTs) after two-years of follow-up. 3. To assess their possible correlation with the class II HLA alleles as well as with several SNPs identified in GWAS related to disease susceptibility.Materials and methodsWe recruited 325 MS patients without DMT (serum samples were collected 1-3 months before starting a therapy) and 295 healthy controls (HC). For each patient we also collected serum samples 6, 12, 18 and 24 months after starting the DMT. EBNA-1 and VCA IgG titers were analyzed by ELISA; 25(OH)D levels were analyzed by immunoassay; HLA DRB1*15:01 allelic variant was analyzed by Taqman technology.Results1. 97.8% (318/325) vs. 87.1% (257/295) positives for EBNA-1 in MS patients and HC, respectively (p

Abstract Epstein–Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls—P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.

En los últimos años comunidades ubicadas en zonas rurales de Colombia han establecido acciones encaminadas a la conservación de recursos naturales que han servido de manera indirecta como una estrategia para reducir los efectos de cambio climático a nivel local. El presente documento da a conocer algunas acciones que han realizado las comunidades de Bahía Málaga ubicadas en el Distrito de Buenaventura para reducir los niveles de deforestación en su territorio y de esta manera contribuir a la conservación y reducción de los efectos de invernadero, además de las acciones de adaptación y mitigación de dichos cambios.

Plain Language Summary This study looked at alemtuzumab, an approved treatment for multiple sclerosis (MS). People who receive alemtuzumab may develop thyroid problems. The researchers wanted to know whether people who developed thyroid problems with alemtuzumab had a worse quality of life compared with those who did not. The researchers measured quality of life using a questionnaire. The questionnaire looked at people’s physical, social, and psychological well-being over 6 years. A total of 811 people with MS treated with alemtuzumab took part in this study. Of these, 469 people (58%) did not develop thyroid problems and 342 people (42%) developed thyroid problems. The thyroid problems were serious in 44 people. The researchers observed that thyroid problems during alemtuzumab treatment did not make quality of life worse in most people. Some people with serious thyroid problems had worsened quality of life; this was mostly among people who required certain treatments for their thyroid problems. Quality of life did not change much in people while the thyroid problems were ongoing. This study shows that thyroid problems after alemtuzumab treatment for MS have little negative impact on quality of life for most people. These findings may help healthcare providers make decisions about MS treatment.

PurposeInterferon beta receptor 2 subunit (IFNAR2) can be produced as a transmembrane protein, but also as a soluble form (sIFNAR2) generated by alternative splicing or proteolytic cleavage, which has both agonist and antagonist activities for IFN-β. However, its role regarding the clinical response to IFN-β for relapsing-remitting multiple sclerosis (RRMS) is unknown. We aim to evaluate the in vitro short-term effects and after 6 and 12 months of IFN-β therapy on sIFNAR2 production and their association with the clinical response in MS patients.MethodsNinety-four RRMS patients were included and evaluated at baseline, 6 and 12 months from treatment onset. A subset of 41 patients were classified as responders and non-responders to IFN-β therapy. sIFNAR2 serum levels were measured by ELISA. mRNA expression for IFNAR1, IFNAR2 splice variants, MxA and proteases were assessed by RT-PCR. The short-term effect was evaluated in PBMC from RRMS patients after IFN-β stimulation in vitro.ResultsProtein and mRNA levels of sIFNAR2 increased after IFN-β treatment. According to the clinical response, only non-responders increased sIFNAR2 significantly at both protein and mRNA levels. sIFNAR2 gene expression correlated with the transmembrane isoform expression and was 2.3-fold higher. While MxA gene expression increased significantly after treatment, IFNAR1 and IFNAR2 only slightly increased. After short-term IFN-β in vitro induction of PBMC, 6/7 patients increased the sIFNAR2 expression.ConclusionsIFN-β administration induces the production of sIFNAR2 in RRMS and higher levels might be associated to the reduction of therapeutic response. Thus, levels of sIFNAR2 could be monitored to optimize an effective response to IFN-β therapy.

Human endogenous retrovirus W family envelope proteins (pHERV-W ENV/syncytin-1) have been repeatedly associated with multiple sclerosis (MS). Here, we have focused on the study of pHERV-W ENV/syncytin-1 expression levels in MS patients (relapsing and progressive forms) and in healthy donors (HD) and on exploring their possible relationship with Epstein-Barr virus (EBV) and human herpesvirus-6A/B (HHV-6A/B). We included blood samples from 101 MS patients and 37 HD to analyze antiviral antibody titers by ELISA and pHERV-W ENV/syncytin-1 expression levels by flow cytometry as well as by qPCR. Patients with relapsing MS forms showed significantly higher pHERV-W ENV/syncytin-1 protein and gene expression levels than HD. Progressive MS patients also showed significantly higher protein and gene expression levels than both HD and relapsing MS patients. Regarding antiviral antibodies titers, anti-HHV-6A/B IgM levels were positively correlated with pHERV-W ENV/syncytin-1 protein expression levels in patients with relapsing MS, while in the progressive forms patients this correlation was found with anti-HHVA/B IgG levels. Therefore, pHERV-W ENV could be involved in MS pathogenesis, playing a role in relapsing and progressive forms. Besides, anti-HHV-6A/B antibodies positively correlated with pHERV-W ENV expression. Further studies are needed to better understand this possible relationship.

Multiple sclerosis is an idiopathic inflammatory disease of the central nervous system and the second most common cause of disability in young adults. Choosing an effective treatment is crucial to preventing disability. However, response to treatment varies greatly between patients. Because of this, accurate and timely detection of individual response to treatment is an essential requisite of efficient personalised multiple sclerosis therapy. Nowadays, there is a lack of comprehensive predictive models of response to individual treatment.This paper arises from the clinical need to improve this situation. To achieve it, all patient's information was used to evaluate the effectiveness of demographic, clinical and paraclinical variables of individual response to fourteen disease-modifying therapies in MSBase, an international cohort. A personalized prediction model to three stages of disease, as a support tool in clinical decision making for each MS patient, was developed applying machine learning and Big Data techniques. These techniques were also used to reduce the data set and define a minimum set of characteristics for each patient. Best predictors for the response to treatment were identified to refine the predictive model. Fourteen relevant variables were selected. A web application was implemented to be used to support the specialist neurologist in real time. This tool provides a prediction of progression in EDSS from the last relapse of an individual patient, and a report for the medical expert.

Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without (M−) lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB), and healthydonors (HD). We conducted an exploratory cross-sectional study with 19 untreated MS patients (M+ = 9 and M− = 10) and 17 HDs. Mitochondrial superoxide anion production and mitochondrial mass in PBMCs were assessed without and with phytohemagglutinin by flow cytometry. The PBMCs’ mitochondrial function was analyzed using Seahorse technology. Superoxide anion production corrected by the mitochondrial mass was higher in MS patients compared with HDs (p = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M− patients. Without stimulus, we observed higher proton leak (p = 0.041) but lower coupling efficiency (p = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR (p = 0.011), and lower stressed OCR/ECAR in the same patients. Exclusively among M+ patients, we described a higher mitochondrial dysfunction in the oldest ones. The mitochondrial impairments found in the PBMCs from MS patients, specifically in M+ patients, could help to better understand the disease’s physiopathology.

Introduction: Amimia is one of the most typical features of Parkinson's disease (PD). However, its significance and correlation with motor and nonmotor symptoms is unknown. The aim of this study is to evaluate the association between amimia and motor and nonmotor symptoms, including cognitive status, depression, and quality of life in PD patients. We also tested the blink rate as a potential tool for objectively measuring upper facial bradykinesia.Methods: We prospectively studied amimia in PD patients. Clinical evaluation was performed using the Unified Parkinson's Disease Rating Scale (UPDRS) and timed tests. Cognitive status, depression, and quality of life were assessed using the Parkinson's Disease Cognitive Rating Scale (PD-CRS), the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR16), and the PDQ-39, respectively. Amimia was clinically evaluated according to item 19 of UPDRS III. Finally, we studied upper facial amimia by measuring resting blink frequency and blink rate during spontaneous conversation.Results: We included 75 patients. Amimia (item 19 UPDRS III) correlated with motor and total UPDRS (r: 0.529 and 0.551 Spearman), and its rigidity, distal bradykinesia, and motor axial subscores (r: 0.472; r: 0.252, and r: 0.508, respectively); Hoehn and Yahr scale (r: 0.392), timed tests, gait freezing, cognitive status (r: 0.29), and quality of life (r: 0.268) correlated with amimia. Blinking frequency correlated with amimia (measured with item 19 UPDRS), motor and total UPDRS.Conclusion: Amimia correlates with motor (especially axial symptoms) and cognitive situations in PD. Amimia could be a useful global marker of overall disease severity, including cognitive decline.

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression.Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from 0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from

Background Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. Objectives To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. Methods Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. Results Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e–4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e–4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r = − 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). Conclusions Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

Human herpesvirus-6A (HHV-6A) and −6B (HHV-6B) might be involved in the etiopathogenesis of multiple sclerosis (MS), especially the HHV-6A. We aim at assessing, for the first time in the scientific literature, the HHV-6A/B microRNAs in MS patients. We analyzed the miRNAs of HHV-6A: miR-U86, and −6B: hhv6b-miR-Ro6-1, −2, −3-3p, −3-5p, and −4 in paired samples of serum and CSF of 42 untreated MS patients and 23 patients with other neurological diseases (OND), using Taqman MicroRNA Assays. Intrathecal HHV-6A/B antibody production and anti-HHV-6A/B IgG/IgM levels in serum were measured. MS clinical data were available. We detected the following miRNAs: hhv6b-miR-Ro6-2 (serum: MS:97.7%, OND:95.7%; CSF: MS:81%, OND:86.4%), 3-3p (serum: MS:4.8%, OND:0%; CSF: MS:2.4%, OND:4.5%), −3-5p (serum: MS:95.2%, OND:91.3%; CSF: MS:50%, OND:54.5%), and miR-U86 (serum: MS:54.8%, OND:47.8%; CSF: MS:11.9%, OND:9.1%). In the serum of the whole population (MS and OND patients) we found a significant correlation between the levels of hhv6b-miR-Ro6-2 and −3-5p (Spearman r = 0.839, pcorr = 3E-13), −2 and miR-U86 (Spearman r = 0.578, pcorr = 0.001) and −3-5p and miR-U86 (Spearman r = 0.698, pcorr = 1.34E-5); also in the CSF, between hhv6b-miR-Ro6-2 and −3-5p (Spearman r = 0.626, pcorr = 8.52E-4). These correlations remained statistically significant when both populations were considered separately. The anti-HHV-6A/B IgG levels in CSF and the intrathecal antibody production in positive MS patients for hhv6b-miR-Ro6-3-5p were statistically significant higher than in the negative ones (pcorr = 0.006 and pcorr = 0.036). The prevalence of miR-U86 (30.8%) in the CSF of individuals without gadolinium-enhancing lesions was higher (p = 0.035) than in the ones with these lesions (0%); however, the difference did not withstand Bonferroni correction (pcorr = 0.105). We propose a role of HHV-6A/B miRNAs in the maintenance of the viral latency state. Further investigations are warranted to validate these results and clarify the function of these viral miRNAs.

Oxidative stress (OS) and inflammation have been related to colorectal cancer (CRC), but the influence of the Mediterranean diet (MD) on these parameters is unknown. Therefore, the aim of this study was to determine the association between adherence to the MD and markers of OS and DNA damage in CRC patients and to study the influence of adherence to the MD on metabolic and tumor-related factors. This prospective observational study included a total of 80 patients diagnosed with CRC. Adherence to the MD was estimated by the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire. The levels of OS markers (catalase, glutathione peroxidase, and glutathione system in serum; 8-oxo-7′8-dihydro-2′-deoxyguanosine and F2-isoprotanes in urine) and tumor and metabolic factors were determined. A total of 51.2% of our CRC patients showed a high adherence to the MD. These patients presented decreased levels of 8-oxodG, increased GPX and HDL–cholesterol levels, and a downward trend in the GSSG/GSH ratio with respect to patients with low adherence to the MD. In addition, a high adherence to the MD was associated with a lower histological grade of the tumor and a lower presence of synchronous adenomas. We conclude that a high adherence to the MD has a protective role against metabolic and oxidative DNA damage and improves antioxidant systems in CRC patients.

Abstract Background It remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients. Methods MS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies. Results By means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value

pHERV-W ENV and syncytin-1, the envelope proteins of the human endogenous retrovirus W family (HERV-W), have been proposed as etiological factors for MS development. In addition, herpesviruses, such as the Epstein-Barr virus (EBV) and the human herpesvirus 6A/B (HHV-6A/B), have been also strongly associated with the disease. This work aims to study the possible link between viral loads and antibody titers against EBV and HHV-6A/B and the pHERV-W ENV/syncytin-1 protein/gene expression. For this purpose, we conducted a 12-month longitudinal study involving 98 RRMS patients. Peripheral blood samples were obtained from each patient. Serum antibody titers against EBV and HHV-6A/B were determined by ELISA, while viral loads were analyzed using qPCR. HLA MS-related alleles were also genotyped. pHERV-W ENV/syncytin-1 protein and gene expression levels in immune cells were assessed by flow cytometry and qPCR, respectively. We found that the 12-month variation of the pHERV-W ENV gene expression levels positively correlated with the variation of the EBV viral load, especially in those patients with high baseline EBV loads. Therefore, these results could support previous studies pointing to the transactivation of pHERV-W ENV by EBV. However, further studies are needed to better understand this possible relationship.

Background Low levels of 25-hydroxyvitamin D (25(OH)D) have been described as one of the possible environmental factors involved in multiple sclerosis (MS) etiopathogenesis. Objectives To study epidemiology of MS and 25(OH)D serum levels of patients in Lanzarote (29°02′06″N), a region with high ultraviolet radiation values during the whole year which is located far apart from Iberian Peninsula (36°–43°N), but without genetic/ethnic differences with it. Methods Incidence in Lanzarote was assessed according to McDonald 2005 criteria between January 2008 and December 2015 and prevalence date was 12/31/15. For 25(OH)D serum levels analyses, samples from 60 MS patients and 60 healthy donors (HD) were collected monthly in a one-year prospective study. Results The prevalence of MS in Lanzarote was 50.0/100,000 and the incidence per year was 2.5/100,000. Median 25(OH)D levels values were 29.1 ng/ml for MS patients (maximum = 36.1 ng/ml, minimum = 22.5 ng/ml) and 27.1 ng/ml for HD (maximum = 34.8 ng/ml, minimum = 22.8 ng/ml). There were no significant differences between 25(OH)D serum levels between MS patients and HD. Conclusions Lanzarote possesses lower prevalence and incidence values than peninsular Spain. Moreover, 25(OH)D serum levels do not differ between MS patients and HD.

Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93–1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.

Although the etiology of multiple sclerosis (MS) is still unknown, it is commonly accepted that environmental factors could contribute to the disease. The objective of this study was to analyze the humoral response to Epstein-Barr virus, human herpesvirus 6A/B and cytomegalovirus, and the levels of 25-hydroxyvitamin D (25(OH)D) and the three main short-chain fatty acids (SCFA), propionate (PA), butyrate (BA) and acetate (AA), in MS patients and healthy controls (HC) to understand how they could contribute to the pathogenesis of the disease. With this purpose, we analyzed the correlations among them and with different clinical variables and a wide panel of cell subsets. We found statistically significant differences for most of the environmental factors analyzed when we compared MS patients and HC, supporting their possible involvement in the disease. The strongest correlations with the clinical variables and the cell subsets analyzed were found for 25(OH)D and SCFAs levels. A correlation was also found between 25(OH)D and PA/AA ratio, and the interaction between these factors negatively correlated with interleukin 17 (IL-17)-producing CD4+ and CD8+ T cells in untreated MS patients. Therapies that simultaneously increase vitamin D levels and modify the proportion of SCFA could be evaluated in the future.

Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results.In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting products were visualized by their different electrophoretic mobilities.Overall, this meta-analysis involved 3200 MS patients and 3069 matched healthy controls and it did not evidence significant association of the LILRA3 deletion [carriers of LILRA3 deletion: p = 0.25, OR (95% CI) = 1.07 (0.95-1.19)], even after stratification by gender and the HLA-DRB1*15:01 risk allele.

Two species of estuary catfish the Arius kessleri (CoCoCo) and the Sciadeops troschelii (Nato) were held in floating net cages at varying densities in estuarine waters of Buenventura Bay-Colombia. After 120 days for the Cococo had weights of 84.1 g Y64 g with densities of 5 and 30 specimen/rn'. The growth average was 0.58-0.39 g/day; the net yield obtained vary from 0.35 to 1.16 Kg/m', the food conversion ratio vary from 3.3 to 5.0 and de survival rate vary from 86% to 100%. With the Nato we obtained weights of 164 and 184 g, beginning with weights of 41 and 108 g their growth average vary from 0.50 to 0.82 g/day. The net yield obtained vary from 0.58 to 0.75 Kg/m' and the survival rate vary from 83% to 100%. From these results we conclude that the two species of catfish studied are strong species but they do not offer good possibilities for fish farming in estuarine waters.

To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up.We collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio).We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344).The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

BACKGROUND: Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. METHODS: A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. RESULTS: Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)]. CONCLUSION: Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

BACKGROUND: Multiple sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV) is a member of type-W endogenous retrovirus family (HERV-W), known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls. RESULTS: 178 MS patients (62.9% women) and 124 controls (56.5% women) were included. MSRV env load (copies/pg of DNA) was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs). MSRV load was more elevated in MS patients than in controls (p = 4.15e-7). MS women presented higher MSRV load than control women (p = 0.009) and MS men also had higher load than control men (p = 2.77e-6). Besides, women had higher levels than men, both among patients (p = 0.007) and controls (p = 1.24e-6). Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively). CONCLUSIONS: MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2(nd) SRCR domain with susceptibility to MS (P max(T) permutation = 1×10(-4)). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. - CD4(+) naïve cells, P = 0.0001; CD8(+) naïve cells, P

BACKGROUND: Human endogenous retroviruses (HERVs) are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS). The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS) performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility. METHODS: Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions) conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942), rheumatoid arthritis (n = 462) and ethnically matched controls (n = 601). Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls. RESULTS: Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI) = 1.5 (1.04-2.17) and 154W/Stop: p = 0.001; OR (95% CI) = 1.6 (1.19-2.16)]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H) = 0.0008; OR(M-H) (95% CI) = 1.22 (1.09-1.38)]. CONCLUSION: Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

BackgroundMultiple sclerosis (MS) is a multifactorial disease with a genetic basis. The strongest associations with the disease lie in the Human Leukocyte Antigen (HLA) region. However, except for the DRB1*15:01 allele, the main risk factor associated to MS so far, no consistent effect has been described for any other variant. One example is HLA-DRB1*03:01, with a heterogeneous effect across populations and studies. We postulate that those discrepancies could be due to differences in the diverse haplotypes bearing that allele. Thus, we aimed at studying the association of DRB1*03:01 with MS susceptibility considering this allele globally and stratified by haplotypes. We also evaluated the association with the presence of oligoclonal IgM bands against myelin lipids (OCMB) in cerebrospinal fluid.MethodsGenotyping of HLA-B, -DRB1 and -DQA1 was performed in 1068 MS patients and 624 ethnically matched healthy controls. One hundred and thirty-nine MS patients were classified according to the presence (M+, 58 patients)/absence (M-, 81 patients) of OCMB. Comparisons between groups (MS patients vs. controls and M+ vs. M-) were performed with the chi-square test or the Fisher exact test.ResultsAssociation of DRB1*03:01 with MS susceptibility was observed but with different haplotypic contribution, being the ancestral haplotype (AH) 18.2 the one causing the highest risk. Comparisons between M+, M- and controls showed that the AH 18.2 was affecting only M+ individuals, conferring a risk similar to that caused by DRB1*15:01.ConclusionsThe diverse DRB1*03:01-containing haplotypes contribute with different risk to MS susceptibility. The AH 18.2 causes the highest risk and affects only to individuals showing OCMB.

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

BACKGROUND: A functional polymorphism located at -1 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves' disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves' disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn's disease (CD) lesions. METHODOLOGY: Genotyping of rs1883832C>T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. PRINCIPAL FINDINGS: The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p = 0.025; OR (95% CI) = 1.12 (1.01-1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p = 0.002; OR (95% CI) = 1.19 (1.06-1.33)]. This increased predisposition was not detected in UC patients [p = 0.5; OR (95% CI) = 1.04 (0.93-1.17)]. CONCLUSION: The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.

En la estación experimental “Santa Lucía” de la Universidad Nacional, ubicada en el cantón de Barva, provincia de Heredia, a una altura de 1200 m.s.n.m., con 19.7°C de temperatura promedio y una precipitación de 2.000mm, se llevó a cabo un ensayo con el fin de evaluar el rendimiento y valor nutritivo potencial del pasto King Grass (Pennisetum purpureum x Pennisetum typhoides). Se usaron cuatro niveles de fertilizante nitrogenado: 0, 100, 200 y 300kg de N Ha-1 y cinco intervalos de corte: 35, 49, 63, 77 y 91 días. Las variables evaluadas fueron: producción de materia seca (kg Ha-1 corte-1), proteína cruda (%), producción de proteína cruda (kg Ha-1 corte-1) y digestibilidad "in vitro" de la materia seca (%). La unidad experimental estuvo constituida por parcelas de 4.5 x 2.25 m y fueron distribuidas en un diseño de parcelas divididas, en bloques al azar. La fertilización nitrogenada incrementó significativamente (P=

204 pollos sexados (machos) de 1 día de edad del híbrido Indian River fueron distribuidos en un diseño irrestricto al azar con 4 tratamientos y 4 repeticiones para evaluar el efecto de diferentes niveles (0, 10, 20, 30%) de pulpa de café deshidratada en la dieta durante las etapas de iniciación (4 semanas) y engorde (3 semanas). Las dietas se balancearon isoproteicas e isocalóricas sobre una base de maíz y soya de acuerdo con los requerimientos nutricionales de los animales para cada etapa. El agua y el alimento fueron ofrecidos ad labitum. Se evaluaron las variables de ganancia de peso, consumo de alimento y conversión alimenticia. Los resultados obtenidos en este trabajo demuestran que la utilización de pulpa de café deshidratada a niveles mayores de 20% de la dieta de pollo de engorde, en ambas etapas, tuvo efectos negativos sobre el consumo de alimento ganancia de peso y conversión alimenticia. También se concluye que los animales tienden a desarrollar una mayor capacidad de utilización de la pulpa en la dieta conforme aumentan de edad y que el nivel máximo de pulpa que se puede incluir en la dieta de pollos de engorde, tanto en iniciación como engorde, sin causar efectos negativos sobre su rendimiento está entre 3,75 y 19.50% de la dieta.

48 white rats (Rattus norvegicus albinus) with an average body weight of 118 g.from both sexes were distributed in a complete randomized design to determine the effect of 3 levels of CaSO4 and 3 levels of Na2SO4 (0.1, 0.3 y 0.5 %) detoxificant agents of the tannins present in the coffee pulp, which was included in the diet at a fixed level of 20%. The experiment last for 28 days and weight gain, feed intake and feed conversion were evaluated. On the third week, during 3 consecutive days, samples of feces were collected to perform digestibility trials of dry matter, crude protein, energy and crude fiber. The results show that any of the sulfate sources at any of the levels used had any effect on the diets with coffee pulp regarding to weight gain, feed intake and fee conversion. The digestibility of the dry matter, crude protein and energy of the diets containing pulp was improved when the 0.1% levels of CaSO4 was used. The levels of 0.3 and 0.5% of the sulfate sources in the diet did not have any positive effect on the performance of the animals; on the contrary, in some cases they caused a decrement in their performance.

Se distribuyeron 84 pollos del híbrido Indian River de 1 día de nacidos, sin sexar de acuerdo a un diseño irrestricto al azar para evaluar el efecto de diferentes niveles de D.L:-metionina sobre la utilización de la pulpa de café deshidratada (PCD) en sus dietas, tanto en el período de iniciación (0-4 semanas) como en el de finalización (5-7 semanas). En la primera etapa las aves permanecieron agrupadas en tres tratamientos sobre una cama de burucha de madera. En la segunda etapa, se trasladaron a baterías metálicas con celdas individuales. Las dietas para ambas etapas se calcularon isoproteicas e isocalóricas según el estado fisiológico de las aves y todas contenían un nivel fijo de 15% PCD. Fueron suplementadas con 0-50 y 100% de D.L:-metionina sobre la cantidad de aminoácido recomendada para cada etapa. El agua y el alimento se suministraron ad libitum. En la última semana se realizó una prueba de metabolismo del nitrógeno. Las variables de rendimiento productivo (ganancia de peso, consumo alimenticio y conversión alimenticia) no difirieron estadísticamente (P 0.05) entre tratamientos, sin embargo, se observó una mejora en la ganancia de peso y conversión de alimento en las aves suplementadas con 50 y 100% del requerimiento de metionina. En cuanto al metabolismo del nitrógeno, no hubo diferencias estadísticas significativas (P 0.05) para las variables de total de excreta producida, utilización de la materia seca y digestibilidad del nitrógeno. La retención del nitrógeno en las aves suplementadas con el nivel más alto de metionina fue superior (P≤ 0.05) a la de las aves sin suplementación e igual a la de 50%. Se concluye que los taninos no son necesariamente el factor más limitante en la utilización de la PCD; otros elementos como el alto contenido de fibra cruda, K+ y otras sustancias tóxicas interfieren.

Un experimento en Cynodon nlenfuensis fue conducido en la Estación Experimental “Santa Lucía-UNA”, Heredia, Costa Rica, cuyos suelos son clasificados como Typic Dystrandept. La temperatura promedio en la zona es de 19.7°C y la precipitación anual de 2000 mm. El pasto fue establecido en 1979 y recibió una fertilización anual de 150kg de N/ha fraccionado después de cada pastoreo, en cantidades iguales por aparto durante la época lluviosa. El manejo de los animales incluyó un sistema rotaciona de 3 días de ocupación y 28 y 35 días de descanso para la época lluviosa y seca, respectivamente, la carga animal promedio fue de 3.5 U.A/ha. Las mediciones se iniciaron en julio de 1982 y concluyeron en diciembre de 1983 e incluyeron las variables Proteína Cruda (%) (P.C), % Materia Seca, Fibra Neutro Detergente (F.N.D.) y Digestibilidad in vitro de la Materia Seca (DIVMS). Los resultados indicaron que las variables P.C., % M.S. y DIVMS fueron afectadas significativamente (P =

Se analizaron por mínimos cuadrados los registros reproductivos y productivos de una granja porcina del norte de la provincia de Heredia, Costa Rica, las razas involucradas en el presente estudio fueron Yorkshire, Landrace, Duroc, Hampshire e Híbridas. El año de parto no afectó significativamente el número de lechones al nacimiento, el número de lechones al destete, el número de lechones muertos del nacimiento al destete, el peso total de la camada al nacimiento, el peso total de la camada a los 56 días, la duración de la lactancia, la duración de la gestación, y el intervalo parto concepción e intervalo entre partos. El efecto de la raza materna fue significativo (P

Se utilizaron 80 pollos de engorde del híbrido comercial Indian River, no sexados, según un diseño irrestricto al azar con 5 tratamientos y 4 repeticiones de 4 animales cada una, para estudiar el efecto de la colina como donador de grupos metilo, sobre la utilización de la pulpa de café deshidratada en sus dietas en el período de iniciación (0-4 semanas). En la tapa de finalización (5-7 semanas) se seleccionaron al azar 40 pollos y se alojaron en jaulas individuales utilizando un diseño factorial (5x2) con 4 repeticiones. A las 7 semanas de edad se realizó una prueba de balance de nitrógeno. Se evaluaron las variables: consumo de alimento, ganancia de peso y conversión alimenticia, en ambas etapas y en la etapa de finalización se evaluó además el consumo de proteína y fibra cruda. El balance de nitrógeno se calculó para cada dieta experimental y se determinó la retención y digestibilidad del nitrógeno y la utilización de la materia seca. En ambas etapas y en el balance de nitrógeno, la inclusión de la pulpa de café tuvo efectos negativos sobre las variables evaluadas. Los diferentes niveles de colina adicionados sobre el requerimiento para cada periodo, no disminuyeron dichos efectos.