Base de Datos de Investigación en Agricultura para el Desarrollo: Resultados preliminares

Comunicación presentada en el I Congreso Investigación en Agricultura para el Desarrollo, celebrado en Madrid el 17 y 18 de octubre de 2011.La investigación en agricultura para el desarrollo en España carece de un organismo o una estructura que coordine la información y la producción científica. El único informe previo donde se analizó la actividad en este ámbito fue el "Informe sobre la Cooperación Universitaria al Desarrollo en al Ámbito Agroalimentario - El caso español", realizado por las fundaciones Triptolemos y Cultura de Paz, correspondiente al año 2006-2007.Este trabajo está financiado por el proyecto AECID CAP10-0080 y la ayuda INIA AC2010-00037.Peer Reviewe

Safety of onasemnogene abeparvovec for patients with spinal muscular atrophy 8.5 kg or heavier in a Global Managed Access Program

BACKGROUND: Spinal muscular atrophy is a rare, neurodegenerative disorder caused by biallelic deletions in the survival motor neuron (SMN1) gene. Onasemnogene abeparvovec is a one-time, intravenous gene replacement therapy designed to deliver the SMN1 transgene. Although available in many geographies, it is not approved globally. The Global Managed Access Program (GMAP) expanded treatment access to patients in countries where treatment was not approved. Previous onasemnogene abeparvovec clinical trials included patients with body weight \u3c8.5 kg. Through GMAP, children weighing ≥8.5 kg received onasemnogene abeparvovec. We describe safety data for heavier patients in GMAP. METHODS: GMAP records were reviewed to identify patients weighing ≥8.5 kg at onasemnogene abeparvovec dosing. To obtain corresponding adverse event (AE) data, the Novartis ARGUS safety database was searched using patient identification numbers and birth dates/dosing dates for any reported AE for GMAP patients. RESULTS: As of September 2, 2021, 102 patients weighing ≥8.5 kg at time of dosing were identified. Fifty-four (53%) had one or more reported AEs. Three patients were reported to be deceased. All three deaths were assessed to be secondary to acute respiratory events. Most (62%) AEs were non-serious. The most frequently reported AEs included increases in hepatic laboratory values, decreased platelets and thrombocytopenia, pyrexia, vomiting, and decreased appetite. CONCLUSIONS: Safety findings for patients weighing ≥8.5 kg administered onasemnogene abeparvovec through GMAP were consistent with those described in clinical trials and included hepatotoxicity, thrombotic microangiopathy, and thrombocytopenia

Macro-Architectures in Spinal Cord Scaffold Implants Influence Regeneration

Abstract Biomaterial scaffold architecture has not been investigated as a tunable source of influence on spinal cord regeneration. This study compared regeneration in a transected spinal cord within various designed-macro-architecture scaffolds to determine if these architectures alone could enhance regeneration. Three-dimensional (3-D) designs were created and molds were built on a 3-D printer. Salt-leached porous poly(ε-caprolactone) was cast in five different macro-architectures: cylinder, tube, channel, open-path with core, and open-path without core. The two open-path designs were created in this experiment to compare different supportive aspects of architecture provided by scaffolds and their influence on regeneration. Rats received T8 transections and implanted scaffolds for 1 and 3 months. Overall morphology and orientation of sections were characterized by H&E, luxol fast blue, and cresyl violet staining. Borders between intact gray matter and non-regenerated defect were observed from GFAP immunolabeling. Nerve fibers and regenerating axons were identified with Tuj-1 immunolabeling. The open-path designs allowed extension of myelinated fibers along the length of the defect both exterior to and inside the scaffolds and maintained their original defect length up to 3 months. In contrast, the cylinder, tube, and channel implants had a doubling of defect length from secondary damage and large scar and cyst formation with no neural tissue bridging. The open-path scaffold architectures enhanced spinal cord regeneration compared to the three other designs without the use of biological factors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63279/1/neu.2007.0473.pd

Rare genetic diseases affecting skeletal development and oral health disparities among children and adolescents: a pathway analysis

Background: To examine the relationships of rare genetic diseases affecting skeletal development, socio-demographic characteristics, and oral health-related behaviours with dental clinical measures in children and adolescents. Methods: A cross-sectional study paired by age, gender and social class included 61 children and adolescents with Osteogenesis Imperfecta (N=40) or mucopolysaccharidoses (N=21) and those without genetic rare diseases (N=60). Participants were selected at two referral hospitals for rare genetic diseases in the city of Belo Horizonte, Brazil. Caregivers completed a questionnaire to obtain age, gender, caregiver’s schooling, social class, patterns of dental attendance and duration of breastfeeding. Oral hygiene, dental caries, dental anomalies and malocclusion were assessed through dental examinations. The relationships between variables were estimated through Pathway analysis using the maximum likelihood method. Results: Rare genetic diseases affecting skeletal development were directly associated with dental caries (β=0.22), dental anomalies (β=0.36) and malocclusion (β=0.29). They were also inversely linked to a preventive pattern of dental attendance (β=-0.25). Rare genetic diseases affecting skeletal development were associated with poor oral hygiene (β=0.28) and shorter breastfeeding duration (β=-0.21). Rare genetic diseases affecting skeletal development were linked indirectly with dental caries, a reduced pattern of dental attendance and poor oral hygiene (β=0.43). Patterns of dental attendance mediated the link between rare genetic diseases affecting skeletal development and malocclusion (β=-0.05). Conclusion: Rare genetic diseases affecting skeletal development were associated with poor oral health. Patterns of dental attendance and poor oral hygiene mediated the link between rare genetic diseases affecting skeletal development and dental clinical measures

A biochemical and ultrastructural evaluation of the type 2 Gaucher mouse

Gaucher mice, created by targeted disruption of the glucocerebrosidase gene, are totally deficient in glucocerebrosidase and have a rapidly deteriorating clinical course analogous to the most severely affected type 2 human patients. An ultrastructural study of tissues from these mice revealed glucocerebroside accumulation in bone marrow, liver, spleen, and brain. This glycolipid had a characteristic elongated tubular structure and was contained in lysosomes, as demonstrated by colocalization with both ingested carbon particles and cathepsin D. In the central nervous system (CNS), glucocerebroside was diffusely stored in microglia cells and in brainstem and spinal cord neurons, but not in neurons of the cerebellum or cerebral cortex. This rostralcaudal pattern of neuronal lipid storage in these Gaucher mice replicates the pattern seen in type 2 human Gaucher patients and clearly demonstrates that glycosphingolipid catabolism and/or accumulation varies within different brain regions. Surprisingly, the cellular pathology of tissue from these Gaucher mice was relatively mild, and suggests that the early and rapid demise of both Gaucher mice and severely affected type 2 human neonates may be the result of both a neurotoxic metabolite, such as glucosylsphingosine, and other factors, such as skin water barrier dysfunction secondary to the absence of glucocerebrosidase activity

Identification of areas for improvement in the management of bone metastases in patients with neuroendocrine neoplasms

Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs). Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement. Methods: A retrospective study of all patients with NENs, except Grade 3 (G3) lung NENs (April 2002-March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS v23.0/STATA v12. Results: Of 1212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-entero-pancreatic primary (49%, n=42) followed by lung (25%, n=21), unknown primary (20%, n=17), and “others” (6%, n=5). Two-thirds (n=57) had G1-2 neuroendocrine tumours, and 41% (n=35) had functional tumours. Overall, 28% (n=24) presented with synchronous BMs at first NEN diagnosis, and 55% (n=47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n=38), median time to development of BMs was 14.0 months. BMs were ‘widespread’ in 61% (n=52). Although only 22% (n=19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n=37). Radiotherapy and bisphosphonates were used in 34% (n=29) and 22% (n=19), respectively. Surgery was rarely performed (2%, n=2). Median OS from identification of BMs was 31.0 months, and 18.9 months from development of BMs-related symptoms. Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients’ quality of life and survival outcomes

Metabolic Syndrome and Risk for Incident Alzheimer's Disease or Vascular Dementia: The Three-City Study

OBJECTIVE—Associations between metabolic syndrome and its individual components with risk of incident dementia and its different subtypes are inconsistent

Determination of parameters for the evaluation of Phosphorus/Calcium metabolism in adult normal dogs

Diseases that facilitate alterations in the metabolism of calcium (Ca) and phosphorus (Pi) are\ndiverse. Knowing and interpreting normal parameters is fundamental to making a diagnosis.\nIn this study both minerals were evaluated in the blood and urine of 52 healthy adult dogs in\nthree age ranges in years old (group A: from 1 to 5, group B: from 6 to 10, and group C: older\nthan 10).\nCalcium levels exhibited no significant difference across age groups. A significant increase (p = 0.03)\nin phosphorus was found in group C in relation to the other two groups.\nBased on the elimination of both minerals through the urine, evaluated from the fractional\nexcretion (DIP and DICa) and the relation Ca or Pi / Creatinine, a non-significant tendency\nof a lower elimination of Pi through urine was observed, according to DIP values of group C\n(p = 0.055).\nThe values of DIP and DICa were correlated with the ones in Pi or Ca/Cr in urine (r = 0.9, p < 0.0001).\nThese results allow us to infer that the mineral/Cr relation can be used when evaluating\nelimination by urine. The age range must be taken into account when interpreting results of\nphosphorus in blood and urine, since groups older than 10 years old have higher minimum\nand maximum threshold levels than the other two groups.Fil: Martiarena, B. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Clínica Médica de Pequeños Animales; ArgentinaFil: Castillo, V. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Pequeños Animales. Unidad de Endocrinología; ArgentinaFil: Regonat, M. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Patología Clínica; ArgentinaFil: Regonat, M. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Pequeños Animales. Unidad de Laboratorio; ArgentinaFil: Quintana, H. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Nutrición; ArgentinaFil: Quintana, H. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Pequeños Animales. Unidad de Nutrición; ArgentinaFil: Brandi, G. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Patología Clínica; ArgentinaFil: Brandi, G. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Pequeños Animales. Unidad de Laboratorio; ArgentinaFil: Lamarca, G. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Clínica Médica de Pequeños Animales; ArgentinaFil: Molina, E. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Hospital Escuela de Pequeños Animlaes. Unidad de Nefrología y Urología; ArgentinaFil: Ruidiaz, V. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Clínica Médica de Pequeños Animales; ArgentinaFil: Visintini, A. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Clínica Médica de Pequeños Animales; ArgentinaLas enfermedades que alteran el metabolismo fósforo (Pi)/calcio (Ca) son variadas. Para\ndiagnosticarlas es necesario conocer e interpretar parámetros normales. Se estudiaron ambos\nminerales, en sangre y orina, en 52 perros adultos sanos, agrupados según rango etario en años:\nGA de 1 a 5; GB de 6 a 10 y GC ? de 10.\nNo se encontraron diferencias significativas para la calcemia entre los grupos. Hubo un\nincremento significativo para la fosfatemia (p 0.03) y el producto Ca x Pi (p 0.02) en el GC\nrespecto al resto.\nDe la eliminación de ambos minerales en orina, evaluada mediante la excreción fraccional (DIP\ny DICa) y por la relación Calcio o fósforo/creatinina, se observó una tendencia, no significativa,\na una menor eliminación de fósforo, según los valores de DIP en el grupo C (p 0.055). Los\nvalores de DIP y DICa se correlacionaron con los de Fósforo o Calcio/Creatinina (r 0.9, p < 0.0001),\nhaciendo que dichas relaciones pueden ser utilizadas para evaluar la excreción urinaria.\nEl rango etario debe tenerse en cuenta para interpretar resultados del fósforo en sangre y orina,\ndado que los valores de cortes mínimos y máximos son más elevados en los mayores de 10 años

RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models

Preeclampsia, with the hallmark features of new-onset hypertension and proteinuria after 20 weeks of gestation, is a major cause of fetal and maternal morbidity and mortality. Studies have demonstrated a role for the renin-angiotensin system (RAS) in its pathogenesis; however, small-molecule RAS blockers are contraindicated because of fetal toxicity. We evaluated whether siRNA targeting maternal hepatic angiotensinogen (Agt) could ameliorate symptoms of preeclampsia without adverse placental or fetal effects in 2 rodent models. The first model used a cross of females expressing human Agt with males expressing human renin, resulting in upregulation of the circulating and uteroplacental RAS. The second model induced ischemia/reperfusion injury and subsequent local and systemic inflammation by surgically reducing placental blood flow midgestation (reduced uterine perfusion pressure [RUPP]). These models featured hypertension, proteinuria, and fetal growth restriction, with altered biomarkers. siRNA treatment ameliorated the preeclamptic phenotype in both models, reduced blood pressure, and improved intrauterine growth restriction, with no observed deleterious effects on the fetus. Treatment also improved the angiogenic balance and proteinuria in the transgenic model, and it reduced angiotensin receptor activating antibodies in both. Thus, an RNAi therapeutic targeting Agt ameliorated the clinical sequelae and improved fetal outcomes in 2 rodent models of preeclampsia