DEVELOPMENT OF A FINITE ELEMENT TOOL FOR STRESS ANALYSIS OF A SURGICALLY ALTERED FEMUR

This paper reports the development of a tool for analyzing stresses in a surgically altered femur. The three-dimensional FE model incorporates a novel approach to implementing orthotropic and heterogeneous bone properties and non-uniform distributed loading. The model contains cortical, cancellous, and subchondral bone incorporating experimentally determined mechanical properties to characterize the anisotropy and heterogeneity of the bone. Ligaments and muscles of the joint are represented to more fully describe the loading condition. Use of the tool is demonstrated for an anterior cruciate ligament (ACL) reconstruction with button-type fixation and the knee joint at full extension. The stresses at the tunnel aperture on the femoral cortex produced from the fixation were noticeable for low levels of loading. Forces from the ligaments and muscles had only slight influence on the stresses at the aperture. Repeated compression of the femoral cortex at these stress levels may cause microdamage to the cortex eventually resulting in fatigue failure

Adding Value to Ready-to-Crustacean Products: Process optimization for "entire" crustaceans using novel technologies

El objetivo general de esta Tesis Doctoral fue optimizar y evaluar el potencial de diferentes tecnologías de procesado en la producción de buey de mar (Cancer pagurus) irlandés listo para el consumo. El primer capítulo de introducción general proporciona una visión global de las diferentes estrategias para la conservación de alimentos y de las tecnologías de procesado disponibles actualmente. Además, se lleva a cabo una revisión de la optimización del procesado de alimentos haciendo énfasis en los tratamientos térmicos. Finalmente, este capítulo resume una visión general del buey de mar, su importancia en la Industria Irlandesa y las prácticas actuales para su procesado. Tras el capítulo de introducción, en primer lugar, se caracterizó la principal flora bacteriana responsable de la alteración del buey de mar listo para consumo y su resistencia frente a los tratamientos térmicos. De los resultados obtenidos, se deduce la importancia de Bacillus spp. y Staphyloccocus spp. como los principales microorganismos presentes en el buey de mar listo para el consumo. El estudio de caracterización termobacteriológica demostró que el tratamiento para inactivar Listeria monocytogenes (F70°C7.5°C = 2 minutos), en este tipo de productos, es efectivo para inactivar todas las células vegetativas presentes de manera natural en el buey de mar. Sin embargo, el mismo estudio también reveló que el tratamiento más severo recomendado para inactivar Clostridium botulinum no proteolítico tipo E, en cangrejo, (F90°C8.6°C = 57 minutos) no resultaba suficiente para alcanzar un nivel similar de inactivación (6 ciclos logarítmicos) de la bacteria esporulada más termorresistente aislada del buey de mar, Bacillus weihenstephanensis. Tras la caracterización de la microbiota del buey de mar, se evaluó el potencial de incorporar la tecnología de ultrasonidos para mejorar el cocinado del buey de mar. Los resultados mostraron que la incorporación de ultrasonidos al cocinado del buey de mar mejoraba los fenómenos de transferencia de calor, lo cual permitió reducir el tiempo total del proceso hasta un 15%. Además, los ultrasonidos también probaron ser efectivos para mejorar los procesos de transferencia de masa producidos durante el cocinado mejorando así la limpieza de los cangrejos en el cocinado. Esto permitiría evitar la etapa de limpieza de los cangrejos antes del envasado que se realiza actualmente en el proceso industrial. Dado el potencial de los ultrasonidos para mejorar los procesos de transferencia de masa durante el cocinado del cangrejo, se evaluó su uso para reducir la concentración de cadmio del buey de mar. Los resultados obtenidos probaron que la combinación de los ultrasonidos con temperaturas moderadas de tratamiento es capaz de reducir el contenido total de cadmio del buey de mar hasta un 22.8%, abriendo la posibilidad de utilizar esta tecnología para afrontar este importante reto en la producción de estos productos.Tras la caracterización de las primeras etapas de la producción de buey de mar (cocción y lavado), se realizó un estudio de optimización del segundo tratamiento térmico, la pasteurización, basado en la cinética de cambio de calidad del producto. De los resultados obtenidos, se deduce que el color de la carne blanca es el parámetro de calidad que se ve más afectado debido al tratamiento térmico, por lo que se caracterizó su cinética de cambio de color, utilizándose como indicador para la optimización del proceso. En base a las ecuaciones desarrolladas en este estudio, el tratamiento térmico requerido para inactivar B. weihenstephanensis sería demasiado severo para retener una buena calidad en el producto final pasteurizado. Por este motivo, se evaluó el uso de tecnologías alternativas (Mano-Sonicacion, Mano-Termo-Sonicacion y radiaciones ionizantes aplicando electrones acelerados) para la inactivación de los esporos aislados del buey de mar. La combinación de ultrasonidos con presión y temperatura mostró un efecto sinérgico para la inactivación de las bacterias esporuladas, lo cual permitiría reducir hasta un 80% el tiempo total de procesado manteniendo unos niveles de inactivación adecuados. La irradiación también probó ser una tecnología efectiva para inactivar las bacterias esporuladas a dosis de tratamiento por debajo del límite establecido por la WHO de 10kGy. Además, la irradiación fue la tecnología para la inactivación de bacterias esporuladas menos afectada por cambios en la especie microbiana contaminante o en las condiciones del medio de tratamiento, lo cual reduciría el riesgo sanitario de los productos pasteurizados si se produjese un error al definir el microorganismo diana o en la composición del producto. Los resultados de esta Tesis Doctoral muestran por tanto el potencial del uso de tecnologías de procesado alternativas a los procesos tradicionales, principalmente el calor, para mejorar la producción de buey de mar irlandés listo para su consumo y afrontar sus retos presentes y futuros. The aim of the present study was to optimize and evaluate the potential of novel technological interventions in the production of ready-to-eat Irish edible crab (Cancer pagurus). The Thesis begins with a general overview of food preservation and main characteristics of edible crab including its significance for the Irish seafood industry. An initial study characterized the main microbiota present in raw and ready-to-eat brown crab and their thermal resistance. Results obtained showed the importance of Bacillus spp. and Staphylococcus spp. in these products. Characterisation of bacterial thermal resistance proved the effectiveness of recommended heat treatments to inactivate Listeria monocytogenes (F70°C7.5°C = 2 minutes). However, the study also revealed that the most severe heat treatment currently recommended, which has Clostridium botulinum non-proteolytic type E as a target microorganism (F90°C8.6°C = 57 minutes), is not sufficient to achieve a comparable inactivation (i.e. 6 Log10 cycles) of the most heat resistant bacterial spore isolated from crab samples namely, Bacillus weihenstephanensis. Following the microbial characterization studies, the potential for incorporating ultrasound to improve early stages in ready-to-eat crab production (i.e. the initial cooking step) was evaluated. The application of ultrasound during cooking enhanced the rate of heat transfer, allowing up to a 15% reduction in total cooking time. In addition, ultrasound also proved its efficacy for enhancing mass transfer from the crab to the cooking water. This improved crab cleaning during cooking would in turn allow the omission of the normal post cook cleaning process prior to packaging. Ultrasounds potential to enhance mass transfer from crab to the cooking water also prompted an investigation into its possible use to remove cadmium from crab. Results showed that ultrasound combined with mild temperatures has the capability to reduce the total cadmium content in edible crab by up to 22.8%. The results open the possibility for using ultrasound as alternative to resolve this issue for the crab industry. Following these studies the second heat treatment step (i.e. in-pack pasteurization) of ready-to-eat crab was optimized to minimize the impact of the treatment on the quality of the final product. Results showed that the colour of crab white meat was the parameter most affected by the heat treatment and therefore, a colour change kinetic for these heat induced changes was developed and used as a quality indicator for process optimization. Based on this study an optimal set of treatment conditions were proposed for the inactivation of C. botulinum non-proteolytic type E. However, based on the models developed the required heat treatment for a process which is solely thermal, would be too severe to retain a good quality. This situation would be further aggravated by the requirement for even more severe heat treatments if B. weihenstephanensis is considered as the target microorganism. Therefore, the use of alternative technologies (i.e. mano-sonication, mano-thermo-sonication and electron beam ionizing radiation) for the inactivation of the main bacterial spores isolated from brown crab was also evaluated. The use of ultrasound in combination with pressure and mild temperatures (i.e. Mano-Thermos-Sonication) showed a synergistic effect in terms of bacterial spore inactivation, which in turn would allow a reduction in the total processing time by over a 80% while still maintaining a similar level of inactivation to heat only. The use of irradiation also proved to be an effective technology to inactivate bacterial spores while still remaining below the limit of 10kGy established by WHO. In addition radiation was the technology least affected by changes in bacterial species or treatment media composition. Overall, the results of this thesis shows the potential for a number of alternative technologies and technical interventions to improve the processing of Irish edible crab and address present and future challenges in the production of these ready-to-eat products. <br /

A MICROFLUIDIC MODEL FOR THE MIGRATION OF CHONDROCYTE UNDER PULSED ELECTROMAGNETIC FIELD

ABSTRACT Pulsed electromagnetic field (PEMF) treatment is a potentially non-invasive method for tissue engineering. In this paper, a theoretical model is established to simulate the regeneration of articular cartilage for Osteoarthritis by means of pulsed electromagnetic fields (PEMF). The electrical field, flow field, single particle motion and concentration field during the growth of chondrocyte are obtained by solving the theoretical model numerically, which accounts for cell distribution in the culture dish. The induced electric field strength can be numerically obtained by Maxwell&apos;s equation and then the potential distribution by the Poisson equation and Laplace equation. The chondrocytes can be driven to move once the electric field is built up. In the calculation of the flow field, the continuity and momentum equation are applied to obtain the bulk electroosmotic velocity field which will affect the motion of the charged cell due to viscous drag forces. The motion of a single particle can be obtained by the classic Newton&apos;s second law. In addition to a single particle, the concentration distribution of particles which indicates the migration of chondrocytes can be described by the conservation law of mass. Boundary conditions are required to solve these sets of equations numerically. A comparison between model results and actual experimental data for the growth and migration of chondrocytes is performed. The results presented here allow a better understanding of the role PEMF in the treatment of Osteoarthritis

Metabolic syndrome across Europe: Different clusters of risk factors

BACKGROUND: Metabolic syndrome (MetS) remains a controversial entity. Specific clusters of MetS components - rather than MetS per se - are associated with accelerated arterial ageing and with cardiovascular (CV) events. To investigate whether the distribution of clusters of MetS components differed cross-culturally, we studied 34,821 subjects from 12 cohorts from 10 European countries and one cohort from the USA in the MARE (Metabolic syndrome and Arteries REsearch) Consortium. METHODS: In accordance with the ATP III criteria, MetS was defined as an alteration three or more of the following five components: elevated glucose (G), fasting glucose ≥110 mg/dl; low HDL cholesterol, &lt; 40mg/dl for men or &lt;50 mg/dl for women; high triglycerides (T), ≥150 mg/dl; elevated blood pressure (B), ≥130/≥85 mmHg; abdominal obesity (W), waist circumference &gt;102 cm for men or &gt;88 cm for women. RESULTS: MetS had a 24.3% prevalence (8468 subjects: 23.9% in men vs. 24.6% in women, p &lt; 0.001) with an age-associated increase in its prevalence in all the cohorts. The age-adjusted prevalence of the clusters of MetS components previously associated with greater arterial and CV burden differed across countries (p &lt; 0.0001) and in men and women (p &lt; 0.0001). In details, the cluster TBW was observed in 12% of the subjects with MetS, but was far more common in the cohorts from the UK (32.3%), Sardinia in Italy (19.6%), and Germany (18.5%) and less prevalent in the cohorts from Sweden (1.2%), Spain (2.6%), and the USA (2.5%). The cluster GBW accounted for 12.7% of subjects with MetS with higher occurrence in Southern Europe (Italy, Spain, and Portugal: 31.4, 18.4, and 17.1% respectively) and in Belgium (20.4%), than in Northern Europe (Germany, Sweden, and Lithuania: 7.6, 9.4, and 9.6% respectively). CONCLUSIONS: The analysis of the distribution of MetS suggested that what follows under the common definition of MetS is not a unique entity rather a constellation of cluster of MetS components, likely selectively risky for CV disease, whose occurrence differs across countries

Schistosomiasis Mansoni: Novel Chemotherapy Using a Cysteine Protease Inhibitor

BACKGROUND: Schistosomiasis is a chronic, debilitating parasitic disease infecting more than 200 million people and is second only to malaria in terms of public health importance. Due to the lack of a vaccine, patient therapy is heavily reliant on chemotherapy with praziquantel as the World Health Organization–recommended drug, but concerns over drug resistance encourage the search for new drug leads. METHODS AND FINDINGS: The efficacy of the vinyl sulfone cysteine protease inhibitor K11777 was tested in the murine model of schistosomiasis mansoni. Disease parameters measured were worm and egg burdens, and organ pathology including hepato- and splenomegaly, presence of parasite egg–induced granulomas in the liver, and levels of circulating alanine aminotransferase activity as a marker of hepatocellular function. K11777 (25 mg/kg twice daily [BID]), administered intraperitoneally at the time of parasite migration through the skin and lungs (days 1–14 postinfection [p.i.]), resulted in parasitologic cure (elimination of parasite eggs) in five of seven cases and a resolution of other disease parameters. K11777 (50 mg/kg BID), administered at the commencement of egg-laying by mature parasites (days 30–37 p.i.), reduced worm and egg burdens, and ameliorated organ pathology. Using protease class-specific substrates and active-site labeling, one molecular target of K11777 was identified as the gut-associated cathepsin B1 cysteine protease, although other cysteine protease targets are not excluded. In rodents, dogs, and primates, K11777 is nonmutagenic with satisfactory safety and pharmacokinetic profiles. CONCLUSIONS: The significant reduction in parasite burden and pathology by this vinyl sulfone cysteine protease inhibitor validates schistosome cysteine proteases as drug targets and offers the potential of a new direction for chemotherapy of human schistosomiasis

Ecology and Geography of Plague Transmission Areas in Northeastern Brazil

Plague in Brazil is poorly known and now rarely seen, so studies of its ecology are difficult. We used ecological niche models of historical (1966-present) records of human plague cases across northeastern Brazil to assess hypotheses regarding environmental correlates of plague occurrences across the region. Results indicate that the apparently focal distribution of plague in northeastern Brazil is indeed discontinuous, and that the causes of the discontinuity are not necessarily only related to elevation—rather, a diversity of environmental dimensions correlate to presence of plague foci in the region. Perhaps most interesting is that suitable areas for plague show marked seasonal variation in photosynthetic mass, with peaks in April and May, suggesting links to particular land cover types. Next steps in this line of research will require more detailed and specific examination of reservoir ecology and natural history

Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk

Purpose: To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. Methods: Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). Results: Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (β = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, β = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC) was significantly and negatively influenced by blood GSH levels (β = -0.20, p = 0.042), and positively associated with FRS (β = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (β = -0.83, p = 0.013; and β = -0.22, p = 0.028, respectively). Conclusions: In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

The funding source (British Heart Foundation and UK National Institute for Health Research) provided salaries for research training (FZ, TT, DS, SW), but had no role in study design, collection, analysis, interpretation, writing, or decisions with regard to publication. This work was undertaken at University College London Hospital, which received a proportion of funding from the UK Department of Health National Institute for Health Research Biomedical Research Centres funding scheme. We are grateful to King’s College London Laboratories for processing the collagen biomarker panel

Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration

View full abstracthttps://openworks.mdanderson.org/leading-edge/1055/thumbnail.jp

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P \u3c .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy