An integrated approach to remanufacturing: model of a remanufacturing system

Remanufacturing is the process of rebuilding used products that ensures that the quality of remanufactured products is equivalent to that of new ones. Although the theme is gaining ground, it is still little explored due to lack of knowledge, the difficulty of visualizing it systemically, and implementing it effectively. Few models treat remanufacturing as a system. Most of the studies still treated remanufacturing as an isolated process, preventing it from being seen in an integrated manner. Therefore, the aim of this work is to organize the knowledge about remanufacturing, offering a vision of remanufacturing system and contributing to an integrated view about the theme. The methodology employed was a literature review, adopting the General Theory of Systems to characterize the remanufacturing system. This work consolidates and organizes the elements of this system, enabling a better understanding of remanufacturing and assisting companies in adopting the concept.The authors would like to extend sincere thanks to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for supporting this research topic

Alteraciones en proteínas asociadas al manejo del calcio intracelular en corazón del modelo murino de enfermedad de Fabry

La Enfermedad de Fabry es una patología de almacenamiento lisosomal genética que entre varios órganos, afecta también al tejido cardíaco. Resultados previos de nuestro grupo revelaron menor contractilidad del ventrículo izquierdo, de músculos papilares y de miocitos aislados, asociado a menor amplitud del transitorio de calcio (Ca2+) en el modelo murino de Enfermedad de Fabry (knockout para el gen de alfagalactosidasa A) (RF) en comparación con los de la cepa salvaje (RWT). El objetivo del presente trabajo es analizar el estado de las proteínas asociadas a la homeostasis del Ca2+ miocárdico en corazones de ratones RF y RWT.Facultad de Ciencias Médica

Prevalence of Fabry Disease in Young Patients with Stroke in Argentina.

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in youngadults, but the frequency of this association is largely unknown. We estimatedthe prevalence of FD in a nationwide cohort of young adults who had stroke andtransient ischemic attack (TIA) in Argentina. Methods: This was a prospective, multicenterstudy of stroke and FD in young adults (18-55 years) conducted in Argentinabetween 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemicor hemorrhagic stroke within the previous 180 days. FD was diagnosed bymeasuring α-galactosidase A activity (males) and through genetic studies (females).Results: We enrolled 311 patients (54% men, mean age: 41 years). Ischemic eventsoccurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes)had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene.Her only other manifestation of FD was angiokeratoma. Eighteen females hadnonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients hadthe nonpathogenic mutation D313Y, while a third had the likely benign mutationS126G. Conclusions: FD was identified in 1 patient (.3%) in this first LatinAmerican study. The patient presented with a late-onset oligo-symptomatic formof the disease. A large number of nonpathogenic mutations were present in ourcohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment.Fil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; ArgentinaFil: Mazziotti, Julieta. Hospital Británico de Buenos Aires; ArgentinaFil: León Cejas, Luciana. Hospital Británico de Buenos Aires; ArgentinaFil: Zinnerman, Alberto. Hospital Posadas; ArgentinaFil: Bonardo, Pablo. Hospital Británico de Buenos Aires; ArgentinaFil: Fernandez Pardal, M.. Hospital Británico de Buenos Aires; ArgentinaFil: Martinez, A.. Hospital Posadas; ArgentinaFil: Riccio, Patricia. Fundación Favaloro; ArgentinaFil: Ameriso, Sebastián. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bendersky, Eduardo. INAREPS; ArgentinaFil: Nofal, Pedro. Sanatorio Parque Tucumán; ArgentinaFil: Cairola, Patricia. CEMIC; ArgentinaFil: Jure, Lorena. Sanatorio Parque Rosario; ArgentinaFil: Sotelo, Andrea. Sanatorio Adventista del Plata; ArgentinaFil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ceci, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Casas Parera, Ignacio Faustino. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Sánchez Luceros, Analía Gabriela. Academia de Medicina; Argentin

Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative.

OBJECTIVES: The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation. DESIGN AND SETTING: Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists' free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed. RESULTS: A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages. CONCLUSIONS: PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised

Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative

Objectives The PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) initiative aimed to reach consensus among a panel of global experts on early indicators of disease progression that may justify FD-specific treatment initiation. Design and setting Anonymous feedback from panellists via online questionnaires was analysed using a modified Delphi consensus technique. Questionnaires and data were managed by an independent administrator directed by two non-voting cochairs. First, possible early indicators of renal, cardiac and central/peripheral nervous system (CNS/PNS) damage, and other disease and patient-reported indicators assessable in routine clinical practice were compiled by the cochairs and administrator from panellists’ free-text responses. Second, the panel scored indicators for importance (5-point scale: 1=not important; 5=extremely important); indicators scoring ≥3 among >75% of panellists were then rated for agreement (5-point scale: 1=strongly disagree; 5=strongly agree). Indicators awarded an agreement score ≥4 by >67% of panellists achieved consensus. Finally, any panel-proposed refinements to consensus indicator definitions were adopted if >75% of panellists agreed. Results A panel of 21 expert clinicians from 15 countries provided information from which 83 possible current indicators of damage (kidney, 15; cardiac, 15; CNS/PNS, 13; other, 16; patient reported, 24) were compiled. Of 45 indicators meeting the importance criteria, consensus was reached for 29 and consolidated as 27 indicators (kidney, 6; cardiac, 10; CNS/PNS, 2; other, 6; patient reported, 3) including: (kidney) elevated albumin:creatinine ratio, histological damage, microalbuminuria; (cardiac) markers of early systolic/diastolic dysfunction, elevated serum cardiac troponin; (CNS/PNS) neuropathic pain, gastrointestinal symptoms suggestive of gastrointestinal neuropathy; (other) pain in extremities/neuropathy, angiokeratoma; (patient-reported) febrile crises, progression of symptoms/signs. Panellists revised and approved proposed chronologies of when the consensus indicators manifest. The panel response rate was >95% at all stages. Conclusions PREDICT-FD captured global opinion regarding current clinical indicators that could prompt FD-specific treatment initiation earlier than is currently practised.Instituto de Estudios Inmunológicos y Fisiopatológico

Gaucher disease-associated alterations in mesenchymal stem cells reduce osteogenesis and favour adipogenesis processes with concomitant increased osteoclastogenesis

Gaucher disease (GD) is caused by pathogenic mutations in GBA1, the gene that encodes the lysosomal enzyme β-glucocerebrosidase. Until now, treatments for GD cannot completely reverse bone problems. The aim of this work was to evaluate the potential of MSCs from GD patients (GD MSCs) to differentiate towards the osteoblast (GD Ob) and adipocyte (GD Ad) lineages, and their role in osteoclastogenesis. We observed that GD Ob exhibited reduced mineralization, collagen deposition and alkaline phosphatase activity (ALP), as well as decreased gene expression of RUNX2, COLA1 and ALP. We also evaluated the process of osteoclastogenesis and observed that conditioned media from GD MSCs supernatants induced an increase in the number of osteoclasts. In this model, osteoclastogenesis was induced by RANKL and IL-1β. Furthermore, results showed that in GD MSCs there was a promotion in NLRP3 and PPAR-γ gene expression. Adipogenic differentiation revealed that GD Ad had an increase in PPAR-γ and a reduced RUNX2 gene expression, promoting adipocyte differentiation. In conclusion, our results show that GD MSCs exhibited deficient GD Ob differentiation and increased adipogenesis. In addition, we show that GD MSCs promoted increased osteoclastogenesis through RANKL and IL-1β. These changes in GD MSCs are likely to contribute to skeletal imbalance observed in GD patients.Fil: Crivaro, Andrea Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Bondar, Constanza María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Mucci, Juan Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ormazabal, Maximiliano Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Feldman, Ricardo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Delpino, María Victoria. University of Maryland School of Medicine. Department of Microbiology and Immunology; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentin

Two-Dimensional Speckle Tracking Echocardiography for Early Detection of Myocardial Damage in Young Patients with Fabry Disease

Fabry disease (FD) is characterized by left ventricular hypertrophy (LVH). Conventional echocardiography is not sensitive enough to perform the preclinical diagnosis To assess whether longitudinal myocardial strain of the left ventricle (LV), using speckle tracking, is useful to detect early myocardial involvement in FD. Forty‐four patients with FD who were diagnosed with genetic testing were prospectively included and were compared to a sex‐matched control group. They were divided into three groups: 22 with LVH (Group I), 22 without LVH (Group II), and 22 healthy volunteers (Group III). LV longitudinal strain was measured from the apical views. An ANOVA test was used for multiple comparisons for variables with a normal distribution, and a Kruskal–Wallis test was used for variables with non‐Gaussian distribution. Longitudinal LV strain was different in the three groups: it was ≥−15% in at least one segment in all Group I patients, in 50% of patients of Group II and in no patient of Group III. Seventy percent of the segments with abnormal strain in Group II were located in the basal regions (32/46). These findings show that the presence of at least one strain value ≥−15% demonstrates subclinical myocardial dysfunction in patients with preclinical FD. Longitudinal myocardial LV strain measured with speckle tracking is a useful tool to detect early myocardial involvement in young patients with FD. This information allows the detection and treatment of myocardial dysfunction at an early stage, which is of high clinical importance.Fil: Saccheri, María C.. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Cianciulli, Tomás F.. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Lax, Jorge A.. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Gagliargi, Juan A.. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor "Dr. Cosme Argerich"; ArgentinaFil: Caceres, Guillermo L.. Centro para la Enfermedad de Fabry; ArgentinaFil: Quarin, Alejandra E.. Centro para la Enfermedad de Fabry; ArgentinaFil: Kisinovsky, Issac. Centro para la Enfermedad de Fabry; ArgentinaFil: Rozenfeld, Paula Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Laboratorio de Investigaciones del Sistema Inmune; ArgentinaFil: Reisin, Ricardo C.. Hospital Británico de Buenos Aires; Argentin