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BackgroundIt 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.MethodsMS 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.ResultsBy 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

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The study analyzed, in two years, the effects of breed [Brahman (BHM; n= 65); Braunvieh (BR; n= 56 )], supplementation with Zilpaterol® (ZIL; treated or control), season of birth (spring or autumn) and their interactions on body surface (BS), age (APB), body weight (WPB), body condition (BC), long dorsal muscle (DM) depth, dorsal fat (DF) thickness and serum leptin concentration (LEP) at puberty (PB) of 121 heifers. At PB, BMHs were heavier and older than BRs (376.8 ± 7.4 vs 302.0 ± 6.6 kg; 588.1 ± 14.7 vs 445.5 ± 12.5 days). ZIL increased APB, WPB, BC and DM, but did not affect DF and LEP. BHMs had 18 % more BS than BRs. However, the difference in WPB/BS was only 6.4 %. When metabolic weight (MW) was used as a proportion of BS (MW/BS) instead of WPB, the difference between BHM and BR disappeared ( P >0.05). The DF was 63.7 % higher in BHM than in BR. Those born in spring started PB with 24.4 % less DF than those born in autumn. Most of the BHM heifers (73.8 %) started PB in the months when light hours were increasing ( P <0.05), while in BRs, the beginning of PB was uniformly distributed throughout the year, regardless of the length of light hours; this effect was present in the two years of study. It is concluded that the establishment of puberty is a multifactorial phenomenon; seasonality affects BHM and BR differently and, apparently, BS is an important fac tor, probably associated with efficiency in energy use. This paper reiterates the importance of dorsal fat and documents, for the first time, MW/BS and its association with the establishment of puberty. [ABSTRACT FROM AUTHOR]

Background and Aims CD39/ENTPD1 scavenges pro-inflammatory nucleotides, to ultimately generate immunosuppressive adenosine, which has a central role in immune homeostasis. Global deletion of Cd39 increases susceptibility to experimental colitis while single nucleotide polymorphisms within the human CD39 promoter, and aberrant patterns of expression during experimental hypoxia, predispose to Crohn's disease. We aimed to define the impact of transgenic human CD39 [hTG] overexpression in experimental colitis and to model therapeutic effects using the recombinant apyrase APT102 in vivo. We also determined the in vitro effects of APT102 on phenotypic and functional properties of regulatory T-lymphocytes derived from patients with Crohn's disease. Methods Colitis was induced by administration of dextran sulfate sodium in wild-type [WT] or hTG mice, and, in another model, by adoptive transfer of CD45RBhigh cells with or without WT or hTG regulatory T cells [Treg]. In additional experiments, mice were treated with APT102. The effects of APT102 on phenotype and function of Treg and type-1 regulatory T [Tr1] cells were also evaluated, after purification from peripheral blood and lamina propria of Crohn's disease patients [ n = 38]. Results Overexpression of human CD39 attenuated experimental colitis and protected from the deleterious effects of systemic hypoxia, pharmacologically induced by deferoxamine. Administration of APT102 in vivo enhanced the beneficial effects of endogenous Cd39 boosted by the administration of the aryl hydrocarbon receptor [AhR] ligand unconjugated bilirubin [UCB]. Importantly, supplemental APT102 restored responsiveness to AhR stimulation by UCB in Treg and Tr1 cells, obtained from Crohn's disease patients. Conclusions hCD39 overexpression ameliorated experimental colitis and prevented hypoxia-related damage in vivo. Exogenous administration of APT102 boosted AhR-mediated regulatory effects in vivo while enhancing Treg functions in Crohn's disease in vitro. [ABSTRACT FROM AUTHOR]

Copyright of Revista Cientifica de la Facultade de Veterinaria is the property of Universidad del Zulia, Facultad de Ciencias Veterinarias and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The objective of this work was to estimate the heritability and repeatability of reproductive traits of Holstein cows reared in subtropical conditions. Records from 171 cows were analyzed, which were daughters of 67 sires and 100 dams. The cows were born from 1986 to 2006, in Las Margaritas research station from the Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP), in Hueytamalco, Puebla, Mexico. Genetic parameters were estimated for interval from calving to first registered heat, interval from calving to first registered service, number of services per conception, days open, and calving interval. Variance components for interval from calving to first registered heat, interval from calving to first registered service, days open, and calving interval were estimated with a single-trait repeatability animal model, while variance components for number of services per conception were estimated with a single-trait animal model, which included the direct additive genetic effect as a random effect. Variance components were estimated with derivative- free restricted maximum likelihood using the MTDFREML program. Estimates of heritability were low, from 0,01 (days open) to 0.13 (calving interval). Estimates of repeatability were also low, ranging from 0.11 (interval from calving to first registered service) to 0.16 (days open). In general, estimates of heritability and repeatability obtained are within the interval of estimates reported in the scientific literature. Estimates of genetic parameters indicate that direct response to one-trait selection would be slow. [ABSTRACT FROM AUTHOR]

Se analizaron los registros genealógicos y reproductivos de 151 vacas de a raza Suizo Pardo para estimar la heredabilidad (h2) y el índice de constancia (r) de diferentes indicadores de fertilidad. Las vacas fueron hijas de 49 sementales y 102 madres. El estudio se realizó en el sitio experimental Las Margaritas, en Puebla, México. El pedigri fue el mismo para todas las características, consistió de 287 animales e incluyó madres sin registros y padres. Los parámetros genéticos fueron estimados para tasa de gestación a primer servicio (TG), días al primer calor registrado después del parto (DC), días al primer servicio registrado después del parto (DS), días abiertos (DA) e intervalo entre partos (IEP). Las estimaciones se hicieron en forma independiente para cada característica, con un modelo de repetibilidad que incluyó el efecto genético aditivo individual, asi como el efecto ambiental permanente de la vaca. Los parametros genéticos fueron estimados por medio de maxima verosimilitud restringida. Los estimadores de la varianza del ambiente permanente, en general, fueron mayores que los de a varianza genética aditiva, por l0 que restuvo determinado principalmente por el ambiente permanente. Los estimadores de h2 yr fueron: 0.02 ±0 .06 y 0.16,0.00 ±0.05 y 0.15,0.03 ±0.03 y 0.03,0.00 ±0.03 y 0.14,y 0.03 ±0.07 y 0.12 para DC, DS,TG, DA e IEP, respectivamentte. La selección artificial como una herramienta para inducir cambio genético en las diferentes mediciones de fertilidad seria poco efectiva, ya que la variación genetica es escasa. [ABSTRACT FROM AUTHOR]

Pedigree and reproductive records of 151 Brown Swiss cows were analyzed with the objective of estimating the heritability (h2) and the repeatability (r) for different measures of fertility. Cows were daughters of 49 sires and 102 dams. The study was carried out at Las Margaritas research station located in Puebla, Mexico. The pedigree was the same for all traits; it consisted of 287 individuals, and included dams without records and sires. Genetic parameters were estimated for conception rate at first service (CR), days to first registered heat after calving (OH), days to first registered service after calving (DS), days open (DO), and calving interval (CI). Estimations were made independently for each trait with a repeatability animal model, which included the direct additive genetic effect, as well as the permanent environmental effect of the cow. Genetic parameters were estimated with restricted maximum likelihood. In general, estimates of permanent environmental variance were greater than estimates of additive genetic variance, so that r was mainly determined by permanent environmental effects. Estimates of h2 and were: 0.02 ±0.06 and 0.16, 0.00 ± 0.05 and 0.15, 0.03 ± 0.03 and 0.03, 0.00 ± 0.03 and 0.14,and 0.03 ± 0.07 and 0.12 for DH, OS, CR, DO and CI. Artificial selection as a tool to induce genetic change in measures of fertility studied would be slightly effective because additive genetic variance is scarce. [ABSTRACT FROM AUTHOR]

Crossbreeding allows taking advantage of additive genetic differences between breeds, they also allow making use of heterosis and complementarity. Therefore, it is necessary to generate information on the efficacy of crosses compared to pure breeds under the conditions of interest. The objective was to quantify the impact of additive and non-additive genetic effects for days to first estrus (DFE), days to first service (DFS), days open (DO), services per conception (SPC), calving interval (CI) and gestation length (GL). The productive and genealogical information of females from a diallel between Holstein (HO) and Brown Swiss (BS), a total of 148 cows of the breeds HO (n=43), BS (n=64) and their reciprocal crosses HO-BS (n=20) and BS-HO (n=21), was used. Contrasts were used to estimate individual heterosis and differences between direct genetic effects and between maternal genetic effects based on Dickerson models. The results showed that heterosis and differences between maternal effects were not significant (P>0.05) for any of the traits studied. Differences between direct genetic effects were only important (P<0.05) for SPC and GL. In conclusion, the heterosis generated by the crossbreeding between HO and BS did not influence the reproductive efficiency of females. Maternal effects were not different between HO and BS. Direct genetic effects for SPC and GL favored the BS breed. [ABSTRACT FROM AUTHOR]

Objective: The diagnosis of secondary progressive multiple sclerosis (SPMS) is often established retrospectively leading to a delay in detection. This work presents a clinical care algorithm that aims to facilitate the recognition of the secondary progressive phase of the disease, analyzing its usefulness and the feasibility of its implementation in routine clinical practice., Methods: The algorithm was developed in four phases: 1) choice of validated diagnostic tools for the detection of progression; 2) assessment of these tools based on experience of use, applicability, time consumed, perceived usefulness and suitability for a profile of a patient in transition to SPMS; 3) framework and final sequence of application; 4) feasibility evaluation through application in clinical practice., Results: A hierarchical algorithm was developed with an initial screening phase to detect warning signs and establish suspicion of progression (which included the tests "Your Multiple Sclerosis (Your MS)," "MSProDiscuss," and "Nomogram") and a second phase conditional on a positive result in the first, including a functional examination with the Symbol Digit Modalities Test (SDMT), 9-Hole Peg Test (9-HPT), and Timed 25-Foot Walk (T25FW) tools. The algorithm was applied to 373 patients with Expanded Disability Status Scale (EDSS) ≥ 2. The mean time spent per patient in the screening was eight minutes and 20.4 minutes for the complete algorithm. The perceived usefulness of the process by the neurologists was 3.1 (range of 1-4, with 4 being the maximum). In 46% of the cases, the algorithm detected the need for additional functional exploration., Conclusions: From our experience, this clinical care algorithm is effective and feasible for detecting progression in MS, although its implementation requires proper organization and can be uneven depending on the resources of each center., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: The RetratEMos project was sponsored by Novartis. Financial relationships: José Eustasio Meca-Lallana declare(s) personal fees from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Roche, and Sanofi. Disclosures have been added in the relevant section of the article. Nieves Téllez declare(s) personal fees from Bayer, Biogen, Merck, Novartis, Sanofi, Teva, Roche, and BMS. Disclosures have been added in the relevant section of the article. Lucienne Costa-Frossard declare(s) personal fees and Support for attending advisory boards/travel from Biogen, Sanofi, Merck, Bayer, Novartis, Roche, Teva, BMS, Janssen, Sandoz, Viatris, and Almirall. Disclosures have been added in the relevant section of the article. René Robles declare(s) personal fees from Biogen, Novartis, Bayer, Merck, Sanofi, Roche, Teva, Almirall, and BMS. Disclosures have been added in the relevant section of the article. Lamberto Landete declare(s) personal fees from Almirall, Bayer, Biogen, BMS, Sanofi, Merck, Novartis, UCB Pharma, Roche, and Teva. Disclosures have been added in the relevant section of the article. Pilar Garcés declare(s) employment from Novartis. Disclosures have been added in the relevant section of the article. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Meca-Lallana et al.)

Background: The effect of disease-modifying therapies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is unclear., Objectives: We aim to determine the immunological responses to SARS-CoV-2 in multiple sclerosis (MS) and anti-CD20-treated patients with other autoimmune diseases (AID)., Methods: Humoral and cellular responses we determined before and 30-90 days after vaccination in patients with MS and anti-CD20-treated patients with other AID in two Catalan centers., Results: 457 patients were enrolled. Findings showed that humoral response decreased under anti-CD20s or sphingosine 1-phosphate receptor modulators (S1PRM) and with longer treatment duration and increased after 4.5 months from the last anti-CD20 infusion. Cellular response decreased in S1PRM-treated. Patients on anti-CD20 can present cellular responses even in the absence of antibodies., Conclusion: Anti-CD20s and S1PRM modify the immunological responses to SARS-CoV-2 vaccines.