Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology

To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar

Oleic acid variation and marker-assisted detection of Pervenets mutation in high- and low-oleic sunflower cross

High-oleic sunflower oil is in high demand on the market due to its heart-healthy properties and richness in monounsaturated fatty acids that makes it more stable in processing than standard sunflower oil. Consequently, one of sunflower breeder's tasks is to develop stable high-oleic sunflower genotypes that will produce high quality oil. We analyzed variability and inheritance of oleic acid content (OAC) in sunflower, developed at the Institute of Field and Vegetable Crops, by analyzing F-1 and F-2 progeny obtained by crossing a standard linoleic and high-oleic inbred line. F-2 individuals were classified in two groups: low-oleic with OAC of 15.24-31.28% and high-oleic with OAC of 62.49-93.82%. Monogenic dominant inheritance was observed. Additionally, several molecular markers were tested for the use in marker-assisted selection in order to shorten the period of detecting high-oleic genotypes. Marker F4-R1 was proven to be the most efficient in detection of genotypes with Pervenets (high-oleic acid) mutation

Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial

Background The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia. Methods/Design One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables. Discussion Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.This study was supported by the Consejeria de Turismo, Comercio y Deporte (CTCD-201000019242-TRA), the Spanish Ministry of Science and Innovation (I + D + I DEP2010-15639, grants: BES-2009-013442, BES-2011-047133, RYC-2010-05957, RYC-2011-09011), the Swedish Heart-Lung Foundation (20090635), the Spanish Ministry of Education (AP-2009-3173), Granada Research of Excelence Initiative on Biohealth (GREIB), Campus BioTic, University of Granada, Spain and European University of Madrid. Escuela de Estudios Universitarios Real Madrid. 2010/04RM

Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families

<p>Abstract</p> <p>Background</p> <p>Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the <it>SLX4 </it>gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of <it>SLX4 </it>in German or Byelorussian familial cases of breast cancer without detected mutations in <it>BRCA1 </it>or <it>BRCA2 </it>has been completed, with globally negative results.</p> <p>Methods</p> <p>The genomic region of <it>SLX4</it>, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of <it>BRCA1 </it>or <it>BRCA2 </it>mutations.</p> <p>Results</p> <p>This mutational analysis revealed extensive genetic variation of <it>SLX4</it>, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them.</p> <p>Conclusions</p> <p>Overall, while the results of this study do not identify clearly pathogenic mutations of <it>SLX4 </it>contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.</p

Plan de Acción en España para la erradicación de la poliomelitis: Vigilancia de la Parálisis Flácida Aguda y Vigilancia de Enterovirus en España. Informe 2020

Centro Nacional de Epidemiología y Centro Nacional de Microbiología. ISCIII. Plan de acción en España para la Erradicación de la Poliomielitis. Vigilancia de la Parálisis Flácida Aguda y Vigilancia de Enterovirus en España, Informe año 2020. Madrid, 5 de noviembre de 2021.[ES] En España la situación libre de polio se monitoriza con la vigilancia de Parálisis Flácida Aguda (PFA) en niños menores de 15 años, como recomienda la Organización Mundial de la Salud (OMS). La vigilancia la realizan los servicios de vigilancia autonómicos y la red de laboratorios de PFA y a nivel nacional se coordina en el Centro Nacional de Epidemiología (CNE, ISCIII) y en el Laboratorio de Poliovirus del Centro Nacional de Microbiología (CNM, ISCIII). En el año 2020 en España no hubo casos de poliomielitis. Se notificaron 0,17 casos de PFA por 100.000 niños menores de 15 años, por debajo del objetivo de sensibilidad establecido por la OMS de un caso de PFA al año por cada 100.000 menores de 15 años. Solamente se detectaron enterovirus no-polio (EVNP) en las muestras de dos casos (EV-D68 y EV-B, respectivamente). En España también se realiza la vigilancia de EVNP en otros síndromes neurológicos para complementar el sistema de vigilancia de PFA. En las muestras investigadas en 2020 no se identificó ningún poliovirus y los EVNP más frecuentemente identificados fueron E-18, CV-A6 y E-21. Mientras haya circulación de poliovirus en el mundo hay que mantener activos los sistemas de vigilancia para detectar a tiempo cualquier importación de poliovirus. [EN] Spain monitors its polio-free status by conducting surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age, as recommended by the World Health Organization (WHO). The AFP surveillance is performed by the 19 Regional Epidemiological Surveillance Units and the AFP Surveillance Laboratory Network, coordinated at national level by the National Centre for Epidemiology (CNE. ISCIII) and the National Poliovirus Laboratory at Nacional Center of Microbiology (CNM. ISCIII) respectively. In 2020, no cases of poliomyelitis were reported from clinical surveillance; Spain reported 0.17 non-polio AFP cases per 100,000 children, below the WHO's performance criterion for a sensitive surveillance system (1 non-polio AFP cases per 100,000 children). The non-polio enteroviruses EV-D68, EV-B were identified from clinical specimens collected from AFP cases. Spain also performs enterovirus surveillance to complement the clinical system In 2020, non poliovirus were identified; The non-polioviruses E-18, CV-A6 y E-21 were the most frequently identified serotypes. As long as poliovirus is circulating in the world, surveillance systems must remain active to detect any importation of poliovirus in a timely manner.1. Resumen. 2. Introducción. 3. Resultados de la vigilancia de Parálisis Flácida Aguda (PFA) en España, 2020. 4. Resultados de la vigilancia de enterovirus, España 2020. 5. Resultados de la vigilancia medioambiental de poliovirus. España, 2020. 6. Sistema de Información Microbiológica (SIM). Meningitis por enterovirus. Tendencia. 7. Conclusiones.N

Anthropic resource exploitation and use of the territory at the onset of social complexity in the Neolithic-Chalcolithic Western Pyrenees: a multi-isotope approach

Carbon (δ13C) and nitrogen (δ15N) stable isotope analyses from bone collagen provide information about the dietary protein input, while strontium isotopes (87Sr/86Sr) from tooth enamel give us data about provenance and potential territorial mobility of past populations. To date, isotopic results on the prehistory of the Western Pyrenees are scarce. In this article, we report human and faunal values of the mentioned isotopes from the Early-Middle Neolithic site of Fuente Hoz (Anuntzeta) and the Late Neolithic/Early Chalcolithic site of Kurtzebide (Letona, Zigoitia). The main objectives of this work are to analyze the dietary and territorial mobility patterns of these populations. Furthermore, as an additional aim, we will try to discuss social ranking based on the isotope data and existing literature on this topic in the region of study. Our results show that, based on the bioavailable Sr values, both purported local and non-local humans were buried together at the sites. Additionally, they suggest similar resource consumption based on C3 terrestrial resources (i.e. ovicaprids, bovids, and suids) as the main part of the protein input. Overall, this study sheds light on how individuals from different backgrounds were still buried together and shared the same dietary lifestyle at a time in the Prehistory of Iberia when social complexities started to appear

Pub1p C-Terminal RRM Domain Interacts with Tif4631p through a Conserved Region Neighbouring the Pab1p Binding Site

Pub1p, a highly abundant poly(A)+ mRNA binding protein in Saccharomyces cerevisiae, influences the stability and translational control of many cellular transcripts, particularly under some types of environmental stresses. We have studied the structure, RNA and protein recognition modes of different Pub1p constructs by NMR spectroscopy. The structure of the C-terminal RRM domain (RRM3) shows a non-canonical N-terminal helix that packs against the canonical RRM fold in an original fashion. This structural trait is conserved in Pub1p metazoan homologues, the TIA-1 family, defining a new class of RRM-type domains that we propose to name TRRM (TIA-1 C-terminal domain-like RRM). Pub1p TRRM and the N-terminal RRM1-RRM2 tandem bind RNA with high selectivity for U-rich sequences, with TRRM showing additional preference for UA-rich ones. RNA-mediated chemical shift changes map to β-sheet and protein loops in the three RRMs. Additionally, NMR titration and biochemical in vitro cross-linking experiments determined that Pub1p TRRM interacts specifically with the N-terminal region (1–402) of yeast eIF4G1 (Tif4631p), very likely through the conserved Box1, a short sequence motif neighbouring the Pab1p binding site in Tif4631p. The interaction involves conserved residues of Pub1p TRRM, which define a protein interface that mirrors the Pab1p-Tif4631p binding mode. Neither protein nor RNA recognition involves the novel N-terminal helix, whose functional role remains unclear. By integrating these new results with the current knowledge about Pub1p, we proposed different mechanisms of Pub1p recruitment to the mRNPs and Pub1p-mediated mRNA stabilization in which the Pub1p/Tif4631p interaction would play an important role

Autoregulation in resistance training : addressing the inconsistencies

Autoregulation is a process that is used to manipulate training based primarily on the measurement of an individual's performance or their perceived capability to perform. Despite being established as a training framework since the 1940s, there has been limited systematic research investigating its broad utility. Instead, researchers have focused on disparate practices that can be considered specific examples of the broader autoregulation training framework. A primary limitation of previous research includes inconsistent use of key terminology (e.g., adaptation, readiness, fatigue, and response) and associated ambiguity of how to implement different autoregulation strategies. Crucially, this ambiguity in terminology and failure to provide a holistic overview of autoregulation limits the synthesis of existing research findings and their dissemination to practitioners working in both performance and health contexts. Therefore, the purpose of the current review was threefold: first, we provide a broad overview of various autoregulation strategies and their development in both research and practice whilst highlighting the inconsistencies in definitions and terminology that currently exist. Second, we present an overarching conceptual framework that can be used to generate operational definitions and contextualise autoregulation within broader training theory. Finally, we show how previous definitions of autoregulation fit within the proposed framework and provide specific examples of how common practices may be viewed, highlighting their individual subtleties

Trends in socioeconomic inequalities in cancer mortality in Barcelona: 1992–2003

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to assess trends in cancer mortality by educational level in Barcelona from 1992 to 2003.</p> <p>Methods</p> <p>The study population comprised Barcelona inhabitants aged 20 years or older. Data on cancer deaths were supplied by the system of information on mortality. Educational level was obtained from the municipal census. Age-standardized rates by educational level were calculated. We also fitted Poisson regression models to estimate the relative index of inequality (RII) and the Slope Index of Inequalities (SII). All were calculated for each sex and period (1992–1994, 1995–1997, 1998–2000, and 2001–2003).</p> <p>Results</p> <p>Cancer mortality was higher in men and women with lower educational level throughout the study period. Less-schooled men had higher mortality by stomach, mouth and pharynx, oesophagus, larynx and lung cancer. In women, there were educational inequalities for cervix uteri, liver and colon cancer. Inequalities of overall and specific types of cancer mortality remained stable in Barcelona; although a slight reduction was observed for some cancers.</p> <p>Conclusion</p> <p>This study has identified those cancer types presenting the greatest inequalities between men and women in recent years and shown that in Barcelona there is a stable trend in inequalities in the burden of cancer.</p