Cross-Cultural Association Between Dietary Animal Protein and Hip Fracture: An Hypothesis

Age-adjusted female hip fracture incidence has been noted to be higher in industrialized countries than non-industrialized countries. A possible explanation which has received little attention is that elevated metabolic acid production associated with a high animal protein diet might lead to chronic bone buffering and bone dissolution. In an attempt to examine this hypothesis, cross-cultural variations in animal protein consumption and hip fracture incidence were studied. When female fracture rates derived from 34 published studies in 16 countries were regressed against estimates of dietary animal protein, a strong, positive association was found. This association could not plausibly be explained by variations in either dietary calcium or total caloric intake. Recent studies suggest that the animal protein-hip fracture association could have a biologically tenable basis. We conclude that further study of the metabolic acid-osteoporosis hypothesis is warranted

Doctor of Philosophy

dissertationThis thesis describes the synthesis and properties of polymer or oligonucleotide-modified nanoporous membranes and nanopores which exhibit a response to external stimuli, synthesized with the intention of mimicking biological protein channels. The responsiveness of these systems arises as a function of the polymer or oligonucleotide modifier, which exhibit a change in conformation with exposure to temperature, pH, introduction of a small molecule, or electric potential. First, the transport of ions through supported silica colloidal films modified with poly(L-alanine) on platinum electrodes was studied using cyclic voltammetry. By monitoring the flux of a redox species through the polymer-modified colloidal film it is demonstrated that the polymer expands and contracts when the temperature was increased and decreased, respectively. We also observed an expansion and contraction as the pH was increased and decreased, respectively. Transport of a neutral dye molecule through free-standing silica colloidal films modified with poly(L-alanine) was also studied. As noted previously, the polymer expands and contracts as the pH is increased and decreased, respectively. Next, the transport was monitored through both silica colloidal film-modified Pt microelectrodes and Pt single nanopore electrodes as an oligonucleotide-based binder, or aptamer, was attached. The aptamer is responsive to a small molecule, cocaine where, in the absence of cocaine, only one "arm" of the aptamer is folded in on itself, leaving the rest of the chain partially unfolded, blocking the nanopores. However, when the cocaine molecule is introduced into solution, the aptamer folds completely in on itself, forming a three-armed structure with the small molecule encapsulated in the middle. This change in conformation is monitored by observing the change in transport of a redox species through the pores as cocaine is introduced into the system. We observed an increase rate of transport as the aptamer bound to cocaine in both systems, consistent with previous reports of aptamer behavior. Next, two types of electro-active polymers, polypyrrole (PPy) or poly(3,4-ethylene-dioxythiophene) (PEDOT), were vapor-phase polymerized onto the surface of a commercially available aluminum oxide nanoporous membrane, or Anodisc. These polymers expand in the reduced state and contract in the oxidized state to produce a responsive membrane

Silica colloidal membranes with enantioselective permeability

Robust mesoporous membranes composed of silica spheres were surface-modified with chiral selector moieties, including small molecules, macrocycles, and polymers. Diffusion rates of enantiomers of a chiral dye through the resulting asymmetrically modified colloidal membranes were measured and the corresponding permselectivities were calculated. The membranes showed enantioselectivities in the range of 1.2-1.8, which were not significantly affected by the structure of the surface-immobilized chiral electors. This selectivity is on par with most reported polymer-based solid membranes and bulk liquid membranes. The enantioselectivity results from the surface-facilitated mechanism of transport of enantiomers through the mesopores. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on Dietary Reference Values for protein

This opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) deals with the setting of Dietary Reference Values (DRVs) for protein. The Panel concludes that a Population Reference Intake (PRI) can be derived from nitrogen balance studies. Several health outcomes possibly associated with protein intake were also considered but data were found to be insufficient to establish DRVs. For healthy adults of both sexes, the average requirement (AR) is 0.66 g protein/kg body weight per day based on nitrogen balance data. Considering the 97.5th percentile of the distribution of the requirement and assuming an efficiency of utilisation of dietary protein for maintenance of 47 %, the PRI for adults of all ages was estimated to be 0.83 g protein/kg body weight per day and is applicable both to high quality protein and to protein in mixed diets. For children from six months onwards, age-dependent requirements for growth estimated from average daily rates of protein deposition and adjusted by a protein efficiency for growth of 58 % were added to the requirement for maintenance of 0.66 g/kg body weight per day. The PRI was estimated based on the average requirement plus 1.96 SD using a combined SD for growth and maintenance.For pregnancy, an intake of 1, 9 and 28 g/d in the first, second and third trimesters, respectively, is proposed in addition to the PRI for non-pregnant women. For lactation, a protein intake of 19 g/d during the first six months, and of 13 g/d after six months, is proposed in addition to the PRI for non-lactating women. Data are insufficient to establish a Tolerable Upper Intake Level (UL) for protein. Intakes up to twice the PRI are regularly consumed from mixed diets by some physically active and healthy adults in Europe and are considered safe

Molecular gated nanoporous anodic alumina for the detection of cocaine

[EN] We present herein the use of nanoporous anodic alumina (NAA) as a suitable support to implement molecular gates for sensing applications. In our design, a NAA support is loaded with a fluorescent reporter (rhodamine B) and functionalized with a short single-stranded DNA. Then pores are blocked by the subsequent hybridisation of a specific cocaine aptamer. The response of the gated material was studied in aqueous solution. In a typical experiment, the support was immersed in hybridisation buffer solution in the absence or presence of cocaine. At certain times, the release of rhodamine B from pore voids was measured by fluorescence spectroscopy. The capped NAA support showed poor cargo delivery, but presence of cocaine in the solution selectively induced rhodamine B release. By this simple procedure a limit of detection as low as 5 × 10−7 M was calculated for cocaine. The gated NAA was successfully applied to detect cocaine in saliva samples and the possible re-use of the nanostructures was assessed. Based on these results, we believe that NAA could be a suitable support to prepare optical gated probes with a synergic combination of the favourable features of selected gated sensing systems and NAA.We thank Projects MAT2015-64139-C4-1-R and TEC2015-71324-R (MINECO/FEDER), the Catalan Government (Project 2014 SGR 1344), the ICREA (ICREA2014 Academia Award) and the Generalitat Valenciana (Project PROMETEOII/2014/047) for support. We also thank to the Agencia Espanola del Medicamento y Productos Sanitarios for its concessions. A.R. thanks the UPV for her predoctoral fellowship. The authors also thank the Electron Microscopy Service at UPV for support.Ribes, À.; Xifre Perez, E.; Aznar, E.; Sancenón Galarza, F.; Pardo Vicente, MT.; Marsal, LF.; Martínez-Máñez, R. (2016). Molecular gated nanoporous anodic alumina for the detection of cocaine. 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Stimulus-response mesoporous silica nanoparticle-based chemiluminescence biosensor for cocaine determination. Biosens. Bioelectro. 75, 8–14 (2016).Pascual, L. L. et al. Oligonucleotide-Capped Mesoporous Silica Nanoparticles as DNA-Responsive Dye Delivery Systems for Genomic DNA Detection. Chem. Commun. 51, 1414–1416 (2015).Qian, R., Ding, I. & Ju, H. Switchable Fluorescent Imaging of Intracellular Telomerase Activity Using Telomerase-Responsive Mesoporous Silica Nanoparticle. J. Am. Chem. Soc. 135, 13282–13285 (2013).Ren, K., Wu, J., Zhang, Y., Yan, F. & Ju, H. Proximity Hybridization Regulated DNA Biogate for Sensitive Electrochemical Immunoassay. Anal. Chem. 86, 7494–7499 (2014).Chen, Y., Santos, A., Wang, Y., Wang, C. & Losic, D. Biomimetic Nanoporous Anodic Alumina Distributed Bragg Reflectors in the Form of Films and Microsized Particles for Sensing Applications. ACS Appl Mater Interfaces. 7, 19816–19824 (2015).Aw, M. S., Bariana, M. & Losic, D. In Nanoporous Alumina. Fabrication, Structure, Properties and Applications (ed. Losic, D., Santos, A. ) 319–354 (Springer International Publishing, 2015).Urteaga, R. & Berli, C. L. In Nanoporous Alumina. Fabrication, Structure, Properties and Applications (ed. Losic, D., Santos, A. ) 249–269 (Springer International Publishing, 2015).Vojkuvka, L., Marsal, L. F., Ferré-Borrull, J., Formentin, P. & Pallarés, J. Self-Ordered Porous Alumina Membranes with Large Lattice Constant Fabricated by Hard Anodization. Superlattices Microstruct. 44, 577–582 (2008).De la Escosura-Muñiz, A. & Merkoçi, A. Nanochannels Preparation and Application in Biosensing. ACS Nano. 6, 7556–7583 (2012).Kumeria, T. et al. Nanoporous Anodic Alumina Rugate Filters for Sensing of Ionic Mercury: Toward Environmental Point-of-Analysis Systems. ACS Appl. Mater. Interfaces. 6, 12971−12978 (2014).Santos, A., Kumeria, T. & Losic, D. Nanoporous Anodic Alumina: A Versatile Platform for Optical Biosensors. Materials. 7, 4297–4320 (2014).Ferré-Borrull, J., Pallarès, J., Macías, G. & Marsal, L. F. Nanostructural Engineering of Nanoporous Anodic Alumina for Biosensing Applications. Materials. 7, 5225–5253 (2014).Gong, D., Yadavalli, V., Paulose, M., Pishko, M. & Grimes, C. A. Controlled Molecular Release Using Nanoporous Alumina Capsules. Biomed Microdevices. 5, 75–80 (2003).Alvarez, S. D., Li, C.-P., Chiang, C. E., Schuller, I. K. & Sailor, M. J. A Label-Free Porous Alumina Interferometric Immunosensor. ACSNano. 3, 3301–3307 (2009).Krismastuti, F. S. H., Bayat, H., Voelcker, N. H. & Schönherr, H. Real Time Monitoring of Layer-by-Layer Polyelectrolyte Deposition and Bacterial Enzyme Detection in Nanoporous Anodized Aluminum Oxide Anal. Chem. 87, 3856–3863 (2015).Ma, D.-L. et al. A Luminescent Cocaine Detection Platform Using a Split G-Quadruplex-Selective Iridium (III) Complex and a Three-Way DNA Junction Architecture. ACS Appl. Mater. Interfaces. 7, 19060−19067 (2015).Kohli, P. et al. DNA-Functionalized Nanotube Membranes with Single-Base Mismatch Selectivity. Science 305, 984–986 (2004).Abelow, A. E. et al. Biomimetic glass nanopores employing aptamer gates responsive to a small molecule. Chem. Commun. 46, 7984–7986 (2010).Ma, D.-L., Chan, D. S.-H. & Leung, C.-H. Group 9 Organometallic Compounds for Therapeutic and Bioanalytical Applications. Acc. Chem. Res. 47, 3614–3631 (2014).Wanga, G., Zhua, Y., Chena, L. & Zhanga, X. Photoinduced electron transfer (PET) based label-free aptasensor for platelet-derived growth factor-BB and its logic gate application. Biosens. Bioelectron. 63, 552–557 (2015).Laptenko, O. et al. The p53 C Terminus Controls Site-Specific DNA Binding and Promotes Structural Changes within the Central DNA Binding Domain. Molec. Cell. 57, 1034–1046 (2015).McKeague, M. & DeRosa, M. C. Challenges and Opportunities for Small Molecule Aptamer Development. J. Nucleic Acids. 2012, 1–20 (2012).McKeague, M. et al. 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Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products

Collective Bargaining: A Management View

In the area of grievance and arbitration machinery, unions are demanding protection against damage claims and court actions and insisting that arbitration be the sole and exclusive remedy for all disputes. Not only are unions insisting upon arbitration of grievances arising under the contract, but they are also insisting upon arbitration of other types of disputes growing out of the relationship between the parties, whether covered by the contract or not. Unions also seek immunity from damage claims in the event of so-called wildcat strikes and fiercely resist provisions which would enable management to obtain relief from courts when no-strike clauses are violated. Management is faced with the problem of finding an accommodation between its objectives of operating efficiently, remaining competitive, paying fair wages, granting reasonable fringe benefits,remaining strike-free, and the objectives of the union in getting more pay for employees, protecting jobs and job opportunities, making the union more secure, and obtaining a voice in the running of the business. In a recent negotiation in which the writer was involved, it took two months to settle the so-called non-money issues and only two days to agree upon money matters. It will be the purpose of this article to discuss some of the changes that unions are now seeking and will continue to seek in forthcoming contract negotiations and to suggest some approaches which management may take

Aportación de los Cultivos Celulares (Condocritos) en las Lesiones de las Articulaciones Dañadas. Regeneración del Cartílago. Desde ACI a MACI y desde ICC a IPC. Discurso de Investidura como Doctor Honoris Causa, 12 de Junio de 2015

Medicin