An integrated simulation and optimization model of sheep farms as a tool to explore technical and environmental objectives

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Peritoneal repairing cells: A type of bone marrow derived progenitor cells involved in mesothelial regeneration

The peritoneal mesothelium exhibits a high regenerative ability. Peritoneal regeneration is concomitant with the appearance, in the coelomic cavity, of a free-floating population of cells whose origin and functions are still under discussion. We have isolated and characterized this cell population and we have studied the process of mesothelial regeneration through flow cytometry and confocal microscopy in a murine model lethally irradiated and reconstituted with GFP-expressing bone marrow cells. In unoperated control mice, most free cells positive for mesothelin, a mesothelial marker, are green fluorescent protein (GFP). However, 24 hrs after peritoneal damage, free mesothelin+/ GFP+ cells appear in peritoneal lavages. Cultured lavage peritoneal cells show colocalization of GFP with mesothelial (mesothelin, cytokeratin) and fibroblastic markers. Immunohistochemical staining of the peritoneal wall also revealed colocalization of GFP with mesothelial markers and with procollagen-1 and smooth muscle α-actin. This was observed in the injured area as well as in the surrounding not-injured peritoneal surfaces. These cells, which we herein call peritoneal repairing cells (PRC), are very abundant 1 week after surgery covering both the damaged peritoneal wall and the surrounding uninjured area. However, they become very scarce 1 month later, when the mesothelium has completely healed. We suggest that PRC constitute a type of monocyte-derived cells, closely related with the tissue-repairing cells known as 'fibrocytes' and specifically involved in peritoneal reparation. Thus, our results constitute a synthesis of the different scenarios hitherto proposed about peritoneal regeneration, particularly recruitment of circulating progenitor cells and adhesion of free-floating coelomic cells. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.(Ministerio de Ciencia e Innovación), RD06/0010/0015 (TerCel network, ISCIII), P06-CTS-01614, P08-CTS-03618 (Junta de AndalucÌa) and LSHM-CT-2005–018630 (VI framework, UE)Peer Reviewe

Predictive model to identify multiple failure to biological therapy in patients with rheumatoid arthritis

Despite advances in the treatment of rheumatoid arthritis (RA) and the wide range of therapies available, there is a percentage of patients whose treatment presents a challenge for clinicians due to lack of response to multiple biologic and target-specific disease-modifying antirheumatic drugs (b/tsDMARDs).To develop and validate an algorithm to predict multiple failure to biological therapy in patients with RA.Observational retrospective study involving subjects from a cohort of patients with RA receiving b/tsDMARDs.Based on the number of prior failures to b/tsDMARDs, patients were classified as either multi-refractory (MR) or non-refractory (NR). Patient characteristics were considered in the statistical analysis to design the predictive model, selecting those variables with a predictive capability. A decision algorithm known as 'classification and regression tree' (CART) was developed to create a prediction model of multi-drug resistance. Performance of the prediction algorithm was evaluated in an external independent cohort using area under the curve (AUC).A total of 136 patients were included: 51 MR and 85 NR. The CART model was able to predict multiple failures to b/tsDMARDs using disease activity score-28 (DAS-28) values at 6 months after the start time of the initial b/tsDMARD, as well as DAS-28 improvement in the first 6 months and baseline DAS-28. The CART model showed a capability to correctly classify 94.1% NR and 87.5% MR patients with a sensitivity = 0.88, a specificity = 0.94, and an AUC = 0.89 (95% CI: 0.74-1.00). In the external validation cohort, 35 MR and 47 NR patients were included. The AUC value for the CART model in this cohort was 0.82 (95% CI: 0.73-0.9).Our model correctly classified NR and MR patients based on simple measurements available in routine clinical practice, which provides the possibility to characterize and individualize patient treatments during early stages.© The Author(s), 2022

Trastorno por déficit de atención e hiperactividad dual en niños y adolescentes internados en un centro para el tratamiento de adicciones

Introducción: El trastorno por déficit de atención e hiperactividad es el trastorno psiquiátrico más frecuente en la edad escolar y múltiples estudios han evidenciado que es un factor de riesgo independiente para desarrollar abuso o dependencia de sustancias. El objetivo principal de este trabajo es determinar la frecuencia de este trastorno y otros trastornos externalizantes en niños y adolescentes internados en un centro de referencia, así como el impacto de estas patologías en la escolarización, inicio precoz del consumo de sustancias, caracterización de las conductas adictivas y perfil de los pacientes. Sujetos y métodos: Se analizaron las historias clínicas de la totalidad de niños y adolescentes internados en un centro de referencia durante los meses de junio y julio de 2013, todos ellos con el diagnóstico de trastorno por uso de sustancias. Se realizaron entrevistas estructuradas para los diagnósticos de déficit de atención e hiperactividad y otros trastornos externalizantes. Resultados: Se determinó la presencia de comorbilidad con déficit de atención e hiperactividad en el 40% de los pacientes y de comorbilidad con trastorno disocial en 95% de los pacientes. Los pacientes con déficit de atención e hiperactividad presentaron mayores dificultades en la escolarización y en el inicio precoz en el uso de sustancias. Conclusión: el trastorno por déficit de atención e hiperactividad es frecuentemente minimizado en sus síntomas y sobre todo en las posibles consecuencias negativas para el paciente; si su diagnóstico no se realiza a tiempo, no será posible un buen abordaje terapéutico del niño y adolescente

Reconstructing the annual mass balance of the Echaurren Norte glacier (Central Andes, 33.5° S) using local and regional hydroclimatic data

Despite the great number and variety of glaciers in southern South America, in situ glacier mass-balance records are extremely scarce and glacier–climate relationships are still poorly understood in this region. Here we use the longest (>  35 years) and most complete in situ mass-balance record, available for the Echaurren Norte glacier (ECH) in the Andes at  ∼  33.5° S, to develop a minimal glacier surface mass-balance model that relies on nearby monthly precipitation and air temperature data as forcing. This basic model is able to explain 78 % of the variance in the annual glacier mass- balance record over the 1978–2013 calibration period. An attribution assessment identified precipitation variability as the dominant forcing modulating annual mass balances at ECH, with temperature variations likely playing a secondary role. A regionally averaged series of mean annual streamflow records from both sides of the Andes between  ∼  30 and 37° S is then used to estimate, through simple linear regression, this glacier's annual mass-balance variations since 1909. The reconstruction model captures 68 % of the observed glacier mass-balance variability and shows three periods of sustained positive mass balances embedded in an overall negative trend over the past 105 years. The three periods of sustained positive mass balances (centered in the 1920s–1930s, in the 1980s and in the first decade of the 21st century) coincide with several documented glacier advances in this region. Similar trends observed in other shorter glacier mass-balance series suggest that the Echaurren Norte glacier reconstruction is representative of larger-scale conditions and could be useful for more detailed glaciological, hydrological and climatological assessments in this portion of the Andes

VEGF Gene Expression in Adult Human Thymus Fat: A Correlative Study with Hypoxic Induced Factor and Cyclooxigenase-2

UNLABELLED:It is well known that the adult human thymus degenerates into fat tissue; however, it has never been considered as a potential source of angiogenic factors. Recently, we have described that this fat (TAT) produces angiogenic factors and induces human endothelial cell proliferation and migration, indicating its potential angiogenic properties. DESIGN:Adult thymus fat and subcutaneous adipose tissue specimens were obtained from 28 patients undergoing cardiac surgery, making this tissue readily available as a prime source of adipose tissue. We focused our investigation on determining VEGF gene expression and characterizing the different genes, mediators of inflammation and adipogenesis, and which are known to play a relevant role in angiogenesis regulation. RESULTS:We found that VEGF-A was the isoform most expressed in TAT. This expression was accompanied by an upregulation of HIF-1alpha, COX-2 and HO-1 proteins, and by increased HIF-1 DNA binding activity, compared to SAT. Furthermore, we observed that TAT contains a high percentage of mature adipocytes, 0.25% of macrophage cells, 15% of endothelial cells and a very low percentage of thymocyte cells, suggesting the cellular variability of TAT, which could explain the differences in gene expression observed in TAT. Subsequently, we showed that the expression of genes known as adipogenic mediators, including PPARgamma1/gamma2, FABP-4 and adiponectin was similar in both TAT and SAT. Moreover the expression of these latter genes presented a significantly positive correlation with VEGF, suggesting the potential association between VEGF and the generation of adipose tissue in adult thymus. CONCLUSION:Here we suggest that this fat has a potential angiogenic function related to ongoing adipogenesis, which substitutes immune functions within the adult thymus. The expression of VEGF seems to be associated with COX-2, HO-1 and adipogenesis related genes, suggesting the importance that this new fat has acquired in research in relation to adipogenesis and angiogenesis

Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development.

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.The authors thank Dr. A. Rojas (CABIMER, Sevilla, Spain) and Prof. Thalia Papayannopoulou (University of Washington, WA, USA) for sharing with us the G2- Gata4-Cre and Itga4-floxed mouse lines, respectively. We also thank Vanessa Benhamo (Institut Imagine) for her expert support with HREM. Finally, we thank all members of “DeCA” laboratory (University of Málaga, Málaga, Spain), and the “Heart Morphogenesis” laboratory (Institut Imagine and Institut Pasteur, Paris, France) for their help and fruitful discussions on this paper. This work was supported by the Spanish Ministry of Science, R+D+i National Programme [grants RTI2018-095410-RBI00 and PID2021-122626-OB-I00], Spanish Ministry of Science-ISCIII [grant number RD16/0011/0030], and University of Málaga [grant number UMA18-FEDERJA-146] to [JMPP]; Consejería de Salud y Familias, Junta de Andalucía [grant number PIER-0084- 2019] to [JAGD]; University of Málaga [grant number I Plan Propio-UMA-A.4] to [ARV]; Spanish Ministry of Science, Innovation, and Universities (MCIU) (CIBER CV) [grant numbers PID2019-104776RB-I00 and CB16/11/00399] to [JLDLP].S

Magnesium in Kidney Function and Disease—Implications for Aging and Sex—A Narrative Review

Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012–2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there’s a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration

Aproximació interdisciplinària a l'acció del foc en les inhumacions i aixovars del Neolític antic cardial de Can Sadurní (Begues, Baix Llobregat)

Antolín, F; Ache, M; Bergadà, M.M; Blasco, A; Buxó, R; Edo, M; Gibaja, J.F; Mensua, C; Palomo, A; Piqué, R; Ruiz, J; Saña, M; Verdún, E; Villalba, M.J. 2011 in Blasco, A; Edo, M; Villalba, M.J. (coord). La cova de Can Sadurní i la prehistòria de Garraf. Actes de les Jornades Internacionals de Prehistòria "El Garraf, 30 anys d'investigació arqueològica". Begues, 5 al 7 de desembre de 2008. Col·lecció Actes. EDAR-Hugony editore. Milano. 2011.[EN] This article presents an interdisciplinary study of archaeological materials excavated from the reservoir layer 18 of the cova de Can Sadurní (Begues, Baix Llobregat, Barcelona, Catalunya, Spain). This layer is formed by a deposit coluvional blocks and gravels in a matrix of silty sand with clay. Ceramic materials are ascribed to the ancient neolithic cardial full and one of his datings obtained on grain seed is 5475-5305 cal ANE. The aim of this study answers the question: what is the origin of the whole and the relationship of the materials with fire.[CA] En aquest article es presenta un estudi interdisciplinari de materials arqueològics excavats de la capa de dipòsit 18 de la cova de Can Sadurní (Begues, Baix Llobregat, Barcelona, Catalunya, Espanya). Aquesta capa està formada per un dipòsit de blocs coluvional i graves en una matriu de sorra llimosa amb argila. Els materials ceràmics són atribuïts a l'antic cardial neolítica complet i un dels seus datacions obtingudes en el germen del gra és 5475-5305 cal ANE. L'objectiu d'aquest estudi respon a la pregunta: quin és l'origen del conjunt i la relació dels materials amb foc.Peer Reviewe