An image-based kinematic model of the tibiotalar and subtalar joints and its application to gait analysis in children with Juvenile Idiopathic Arthritis

In vivo estimates of tibiotalar and the subtalar joint kinematics can unveil unique information about gait biomechanics, especially in the presence of musculoskeletal disorders affecting the foot and ankle complex. Previous literature investigated the ankle kinematics on ex vivo data sets, but little has been reported for natural walking, and even less for pathological and juvenile populations. This paper proposes an MRI-based morphological fitting methodology for the personalised definition of the tibiotalar and the subtalar joint axes during gait, and investigated its application to characterise the ankle kinematics in twenty patients affected by Juvenile Idiopathic Arthritis (JIA). The estimated joint axes were in line with in vivo and ex vivo literature data and joint kinematics variation subsequent to inter-operator variability was in the order of 1°. The model allowed to investigate, for the first time in patients with JIA, the functional response to joint impairment. The joint kinematics highlighted changes over time that were consistent with changes in the patient’s clinical pattern and notably varied from patient to patient. The heterogeneous and patient-specific nature of the effects of JIA was confirmed by the absence of a correlation between a semi-quantitative MRI-based impairment score and a variety of investigated joint kinematics indexes. In conclusion, this study showed the feasibility of using MRI and morphological fitting to identify the tibiotalar and subtalar joint axes in a non-invasive patient-specific manner. The proposed methodology represents an innovative and reliable approach to the analysis of the ankle joint kinematics in pathological juvenile populations

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Monolithic triglyceride matrices: a controlled-release system for proteins

Matrices made of glyceryl trimyristate as a bioerodible and biocompatible material were manufactured by compression in dimensions that would still allow an application via injection. Pyranine, as a low molecular hydrophilic compound with a low detection limit, and tetramethylrhodamine labeled bovine serum albumin (TAMRA-BSA), as a high molecular weight (66 kDa) protein compound, served as model drugs for release investigations. In vitro studies with pyranine revealed that release depends substantially on the gelatin content of the matrices, which proved to be a useful tool as a release modifier. The duration of the drug release period can be adjusted to a desired time interval ranging from days to weeks by choosing the right gelatin content. Moreover, results illustrated the importance of the molecular weight and the nature of the compound to be incorporated into such matrices, since investigations with TAMRA-BSA showed a more pronounced burst release and altered release profiles and periods. Experiments with hyaluronidase, which served as a model enzyme to assess the problem of protein integrity in such matrices, suggested that proteins may display sufficient stability during the manufacturing procedure of the cylinders or while in contact with the triglyceride matrices. In addition to in vitro investigations, a study in mice revealed that after 15 days of subcutaneous implantation the matrices showed a good in vivo stability. The main conclusion that could be drawn from these results was that triglycerides are a promising alternative to biodegradable polymers for the development of parenteral release systems for protein and peptide drugs

Producción de compuestos volátiles por enzimas lipasas para quesos en un sistema modelo de leche

El uso de enzimas esterasas/lipasas de diferentes orígenes en la industria quesera es una estrategia muy empleada en algunas tecnologías particulares para potenciar la formación de compuestos aromáticos característicos derivados de la grasa (ácidos grasos, ésteres, cetonas, alcoholes), diversificar el flavor y acelerar la maduración. La actividad de estos biocatalizadores depende del origen de la enzima, concentración y disponibilidad del sustrato y de las condiciones del medio (temperatura, tiempo, pH), entre otros. El objetivo de este trabajo fue evaluar en un sistema modelo de leche la capacidad de la lipasa EstA (E1) de E. faecalis JH2-2 obtenida en forma recombinante en Escherichia coli BL21 (DE3), y de una lipasa comercial de alta pureza de Rhizomucor miehei (E2), de producir compuestos volátiles derivados de la grasa. Para ello, diferentes condiciones fueron ensayadas: contenido de materia grasa de la leche y aplicación de homogeneización para modificar el estado fisicoquímico del sustrato; de esta manera se tienen muestras con 2,8 y 6% y de grasa y homogeneizadas (H) y nativas es decir sin aplicar homogeneización (N). Se evaluó la formación de compuestos del flavor luego de la incubación en condiciones estandarizadas (37°C/3-5h/agitación), por microextracción en fase sólida y cromatografía de gases (SPME-GC/FID). Los perfiles fueron analizados por componentes principales. Las mayores diferencias fueron encontradas para E2 cuando se trabajó con 2.8% grasa, siendo la homogeneización efectiva en disminuir la compartimentalización enzima-sustrato. Se encontraron niveles incrementados de los ácidos butanoico, hexanoico y octanoico, de ésteres etílicos (butanoato, hexanoato y octanoato) y de algunas metilcetonas (acetoína y 2-nonanona) y diacetilo, en H versus N. E1 mostró un comportamiento muy diferente, ya que las diferencias con los controles fueron mínimas. Los resultados obtenidos con la enzima comercial ponen en evidencia la buena performance del sistema modelo propuesto y del procedimiento de trabajo ensayado (aplicación de homogeneización y análisis de perfiles de compuestos voláltiles por SPME) para evaluar actividad de enzimas esterasas/lipasas como estrategia de selección de condiciones que podrían ser utilizadas posteriormente en elaboraciones de quesos.Fil: Vélez, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Wolf, Irma Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Acciarri, Giuliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Espariz, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Magni, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Hynes, Erica Rut. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Perotti, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaXXI Congreso Latinoamericano y del Caribe de Ciencia y Tecnología de Alimentos y XVII Congreso Argentino de Ciencia y Tecnología de AlimentosBuenos AiresArgentinaAsociación Argentina de Tecnólogos AlimentariosAsociación Latinoamericana y del Caribe de Ciencia y Tecnología de Alimento

Study of volatile compounds profiles in milk matrices using Enterococcus faecalis EstA and Rhizomucor miehei lipase

The use of esterase/lipase enzymes of different origins in food industry is a widely employed strategy to enhance the formation of characteristic aromatic compounds derived from fat and diversify flavour. In the present work, we studied EstA enzyme of Enterococcus faecalis and a high purity Rhizomucor miehei lipase (Palatase). EstA was obtained recombinantly in Escherichia coli BL21 (DE3), and optimum esterase activity was detected at pH 6.75 and 40 °C. We evaluated the effect of the enzymes on milk mixtures prepared with different fat contents (2.8 and 6%) and structure (native or homogenized) on volatile compounds profiles. The milk fat structure before and after the application of low homogenization was characterized by dynamic light dispersion and microscopy. Native milk fat mixtures presented particles of 4.6 μm and 184 nm and homogenized mixtures had particles of 1.4 μm and 258 nm; microscopy images were in concordance with these results. Fifteen volatile compounds were identified, including ketones, esters, alcohols, and acids. We showed the key role of milk fat levels and microstructure in the nature of the volatile compounds produced by the R. miehei enzyme. Both in native or homogenized states, the highest content of fat favored a higher production of acids whereas the lowest fat level favored a higher esters production along with a more balanced volatile profile. For EstA enzyme, results showed a limited action on fat, as biosynthesis of esters only increased with the highest fat level homogenized.Fil: Vélez, María Ayelén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Wolf, Irma Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Espariz, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Acciarri, Giuliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Magni, Christian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Hynes, Erica Rut. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Perotti, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; Argentin

Ecological Impact of End-of-Life-Tire (ELT)-Derived Rubbers: Acute and Chronic Effects at Organism and Population Levels

Considering the large amount of tires that reach the end of life every year, the aim of this study was the evaluation of both acute and chronic effects of end-of-life-tire (ELT)-derived rubber granules (ELT-dg) and powder (ELT-dp) on a freshwater trophic chain represented by the green alga Pseudokirchneriella subcapitata, the crustacean Daphnia magna and the teleost Danio rerio (zebrafish). Adverse effects were evaluated at the organism and population levels through the classical ecotoxicological tests. Acute tests on D. magna and D. rerio revealed a 50% effect concentration (EC50) > 100.0 mg/L for both ELT-dg and ELT-dp. Chronic exposures had a lowest observed effect concentration (LOEC) of 100.0 mg/L for both ELT-dg and ELT-dp on P. subcapitata grow rate and yield. LOEC decreased in the other model organisms, with a value of 9.8 mg/L for D. magna, referring to the number of living offspring, exposed to ELT-dg suspension. Similarly, in D. rerio, the main results highlighted a LOEC of 10.0 mg/L regarding the survival and juvenile weight parameters for ELT-dg and a LOEC of 10.0 mg/L concerning the survival and abnormal behavior in specimens exposed to ELT-dp. Tested materials exhibited a threshold of toxicity of 9.8 mg/L, probably a non-environmental concentration, although further investigations are needed to clarify the potential ecological impact of these emerging contaminants