Surface Texture and Micromechanics of Ultra High Molecular Weight Polyethylene (UHMWPE) Orthopaedic Implant Bearings

Tibial bearings of ultra-high molecular weight polyethylene (UHMWPE) were characterized to identify differences in morphology, surface texture (roughness and skewness), and micro-scale mechanical behavior. These orthopaedic implant components were fabricated by direct molding or by machining after isostatic compression molding. Sterilization was by gamma irradiation (3.3 Mrad) in air, followed by shelf aging for 2 years. Comparisons were made between unsterile and sterile bearings to identify differences in structure and properties related to wear debris. Characterization methods included confocal optical microscopy, nanoindentation , small angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and polarized light microscopy. Morphology was compared between bulk and surface (top and bottom) specimens of the bearings. Cryo-microtomy was used to prepare thin specimens transverse to the top surface for polarized microscopy. Nanoindentation was performed on the top bearing surfaces, near areas examined by confocal microscopy. Processing methods affected both small- and large-scale morphology of UHMWPE. Direct molding produced thinner lamellae, thicker long periods, and slightly lower crystallinity than isostatic compression molding. Both bearing types contained a thick interface between the crystalline and amorphous phases. Interfacial free energy varied with interface thickness. Resin particles were consolidated better in direct molded bearings than in machined bearings. Segregated amorphous regions were observed in the machined bearings. Sterilization and shelf aging affected nanometer-scale morphology. Chain scission significantly decreased the interface thickness, causing an increase in lamellar thickness and a small increase in crystallinity. Only a small decrease in the amorphous thickness resulted. Heterogeneous oxidation increased these changes in interface thickness and lamellar thickness at the surfaces. Thin lamellae were created in the direct molded bearing, uniformly through its thickness, following chain scission and crystallization at low temperature. Both surface roughness and morphology affected micromechanical behavior by nanoindentation. Indents must extend deeper than the peak-to-valley height (2 - 11 m) of surface features, near the scale of wear debris. Hardness and elastic modulus correlated with lamellar thickness. Machined bearings were harder and stiffer than direct molded bearings. Sterilization increased lamellar thickness, so properties of the sterile, molded bearing approached those of the unsterile, machined bearing

Design and Validation of Two Predictive Models for Mortality and Readmission Following Surgery in Patients with Liver Cirrhosis

Cirrhosis is the 12th leading cause of death in the United States. By 2020, it is expected to affect more than 1 million Americans. Cirrhosis is a costly, chronic condition requiring frequent hospitalizations and unplanned readmissions. Patients with cirrhosis often require routine surgeries including hernia repair, coronary artery by-pass surgery and orthopedic hip or knee replacements. These procedures present a greater risk of morbidity and mortality for cirrhotic patients, including a 8-fold increase in risk of mortality and higher hepatic decompensation after surgery. Predicting post-operative mortality prior to surgery or post-operative readmission would allow patients and clinicians to make informed decisions that optimize survival and reduce readmission costs. Currently, the MELD score is often used, inappropriately, to assess risk of procedures in patients with decompensated cirrhosis. However, no models exist that predict mortality or readmission among patients with cirrhosis. This study aimed to develop and validate two predictive models; one for mortality among all patients with cirrhosis undergoing surgery; the other will predict readmission among cirrhosis patients discharged alive after the index surgery. Each two model was then compared to the MELD score. The NSQIP Mortality Model was significantly better than the MELD score at predicting mortality (p<0.001) and had an area under the receiver operating characteristic (AUROC) curve of 0.84. The readmission model was also significantly better than the MELD score (p<0.001), with an AUROC of 0.75. Both models provide the basis for developing two decision tools that can assist clinicians and patients in making informed decisions that optimize survival and reduce unplanned readmissions.Doctor of Philosoph

Consumption orientations may support (or hinder)transitions to more plant-based diets

There have been increasing calls for triggering and sustaining a large-scale transition toward healthier and more sustainable food systems. To help materialize this transition, the present work aims to inform efforts for developing, marketing and promoting plant-based meals and plant-forward lifestyles, following a consumption-focused approach. The findings (N participants = 1600, Portugal; 52.6% female, M age = 48.30) allowed to identify trends and differences on three sets of variables – (a)current eating habits (i.e., meat, fish, and plant-based meals), (b)consumer willingness to change (i.e., reduce meat consumption, follow a plant-based diet, maintain the status quo), and (c)enablers for eating plant-based meals more often (i.e., capability, opportunity, motivation)–, considering consumer orientations toward consumption in general, and food consumption in particular. Taken together, the results suggested that some consumption orientations were aligned with the transition to more plant-based diets (e.g., food orientation toward naturalness), others were open to – but not yet materialized in – the transition (e.g., general orientation toward consumption as exploration), and still others were in tension with the transition (e.g., food orientation toward pleasure). The discussion calls for developing and testing pathways to reduce meat consumption and increase plant-based eating which capture and build upon a range of consumption orientations, rather than against them.info:eu-repo/semantics/acceptedVersio

Beyond immune escape:a variant surface glycoprotein causes suramin resistance in Trypanosoma brucei

Suramin is one of the first drugs developed in a medicinal chemistry program (Bayer, 1916), and it is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by Trypanosoma brucei rhodesiense. Cellular uptake of suramin occurs by endocytosis, and reverse genetic studies with T. b. brucei have linked downregulation of the endocytic pathway to suramin resistance. Here we show that forward selection for suramin resistance in T. brucei spp. cultures is fast, highly reproducible and linked to antigenic variation. Bloodstream-form trypanosomes are covered by a dense coat of variant surface glycoprotein (VSG), which protects them from their mammalian hosts' immune defenses. Each T. brucei genome contains over 2000 different VSG genes, but only one is expressed at a time. An expression switch to one particular VSG, termed VSGSur , correlated with suramin resistance. Reintroduction of the originally expressed VSG gene in resistant T. brucei restored suramin susceptibility. This is the first report of a link between antigenic variation and drug resistance in African trypanosomes

Leadership Opportunities in the Emerging Field of Translational Science: Forging a Path for Biomarkers from Academic Discovery to Clinical Laboratory Use

Translational science is focused on improving human health by bringing scientific discoveries from the academic research laboratory (bench) into clinical practice (bedside). In September 2004, the National Institutes of Health established a roadmap for medical research to overcome major hurdles of moving technologies from bench to bedside. Since then there have been great successes in the areas of therapeutics, medical devices and community interventions. However, translation of biomarkers from discovery to the clinical laboratory has remained sluggish. Rapid translation calls for a more defined path from academic discovery to clinical use. Leadership opportunities in academia and industry abound as this path is forged in the clinical diagnostic arena. Rapid translation of laboratory diagnostics is vital to patient care. Clinical laboratory diagnostics are primary tools used by clinicians to make decisions impacting patient care. Proteomic and genomic discoveries in the academic arena are vast yet rarely move into clinical validation and transfer to industry due to intellectual property disputes, scarce funding resources for validation, method development expertise and lack of communication between academia and industry. The objective of this paper is to define the barriers that exist for a biomarker along the path to a widely adopted assay in the clinical laboratory, offer solutions and define potential leadership opportunities in this emerging field. Barriers to translation of biomarkers from discovery to clinical use continue to persist. There may be limited communication between academic researchers and clinical laboratory leaders. Methods used to discover useful biomarkers may not be suitable for clinical laboratory high-volume testing. Often, development, method and clinical validation of the biomarker are necessary before an industry partner is interested in investing in the high-risk/high-return discovery as a potential clinical diagnostic assay. It has been challenging to secure funding for prospective clinical validation of diagnostic assays in the academic setting. Additionally, there is a gap in training and personnel at the academic level to take a biomarker beyond the discovery phase. The expertise to develop methods utilized in clinical laboratories lies in the hands of industry research and development experts cautious to invest in early method development of a 3 biomarker without evidence of its performance in the target population. Thus, many biomarkers never make it out of the discovery phase. A review of current literature reveals great opportunities exist for collaboration between clinical laboratories, academic researchers and industry leaders to move biomarkers rapidly from bench to bedside. During review of the literature and my own experience translating biomarkers for clinical use, it was discovered that no curriculum exist academia to train future scientists for method development on platforms suitable for clinical laboratory use. Just as communication has improved between basic science researchers and clinicians to facilitate translation of therapeutics into practice, so must the clinical laboratory, diagnostic industry and academia collaborate to form a clear path to translate biomarkers into useful clinical tools. Barriers and solutions to translation of biomarkers are discussed and recommendations provided for forging a clear path for biomarkers using the existing NIH Clinical and Translational Science infrastructure across college campuses in the United States as well as the Early Detection Research Network and the Biomarker Consortium resources. By rapidly delivering efficacious and effective diagnostic tools to clinicians, the implications for public health are many. Sensitive diagnostic laboratory assays may prevent costly treatment and extend quality life years. Screening assays may reduce the incidence of disease and allow effective interventions. Prognostic assays may assist patients and clinicians in making decisions about costly and high-risk interventions.Master of Public Healt

A Swine Model of Soy Protein-Induced Food Allergy: Implications in Human and Swine Nutrition

There is extensive literature on the development and management of food allergy, but some basic questions such as why some proteins are allergenic while closely related proteins from other species are not allergenic, remain to be answered. This paper is not a detailed review of food allergies, but rather an overview of current knowledge regarding soy food allergies, with a focus on the pig as a model for the study of soy allergies and with additional information on how soy allergies and use of soybean-sourced feed can affect production animal agriculture

A Swine Model of Soy Protein-Induced Food Allergy: Implications in Human and Swine Nutrition

There is extensive literature on the development and management of food allergy, but some basic questions such as why some proteins are allergenic while closely related proteins from other species are not allergenic, remain to be answered. This paper is not a detailed review of food allergies, but rather an overview of current knowledge regarding soy food allergies, with a focus on the pig as a model for the study of soy allergies and with additional information on how soy allergies and use of soybean-sourced feed can affect production animal agriculture

Assessing the Future of the Bioeconomy in Greene County, Iowa

The bioeconomy is changing the landscape of some U.S. Corn Belt states. Not surprisingly, Iowans are experiencing significant effects from the developing ethanol industry, and many, including Greene County residents, are becoming more aware of bioeconomic trends. Knowing that positive and negative impacts arise as bioeconomic initiatives evolve in Iowa, this case study addresses the following central question: What should Greene County do to minimize the potentially negative impacts and maximize the positive prospects of the bioeconomy? The phases of the study were: (1) analyze current conditions with respect to feedstock potential and transportation; (2) determine residents’ opinions about topics related to the bioeconomy, such as environment, water resources, and livestock; and (3) assess potential impacts and make recommendations. Geographic information systems (GIS) technology was used in part to address these phases. This study represents a replicable first step for analyzing growth of the bioeconomy in a rural Midwest county

Transgenic soybean production of bioactive human epidermal growth factor (EGF)

Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother's breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N' terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform