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

Limiea Woolf, Mildred E. Mowe, Madge E. Iverson, Cynthia Cynthia J. Willett, Reve J. Abelow, Ruth S. Elderkin, Carl Locke, Rev. Brown, Barbara Dascher, John H. Doscker to James Meredith (7 October 1962)

https://egrove.olemiss.edu/mercorr_pro/2039/thumbnail.jp

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

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

A multi-centre randomized controlled trial comparing electrothermal arthroscopic capsulorrhaphy versus open inferior capsular shift for patients with shoulder instability: Protocol implementation and interim performance: Lessons learned from conducting a multi-centre RCT [ISRCTN68224911; NCT00251160]

BACKGROUND: The shoulder is the most frequently dislocated joint in the body. Multiple causes and pathologies account for the various types of shoulder instability. Multi-directional instability (MDI) and multi-directional laxity with antero-inferior instability (MDL-AII) are similar in pathology, less common and more difficult to treat. These instabilities are caused by ligamentous capsular redundancy. When non-operative management fails for these patients, quality of life is significantly impaired and surgical treatment is required to tighten the ligaments and joint capsule. The current reference (gold) standard treatment for MDI/MDL-AII is an open inferior capsular shift (ICS) surgical procedure. An alternative treatment involves arthroscopic thermal shrinkage of redundant capsular tissue to tighten the joint. However, there is a lack of scientific evidence to support the use of this technique called, electrothermal arthroscopic capsulorrhaphy (ETAC). This trial will compare the effectiveness of ETAC to open ICS in patients with MDI and MDL-AII, using patient-based quality of life outcome assessments. METHODS: This study is a multi-centre randomized clinical trial with a calculated sample size of 58 patients (p = 0.05, 80% power). Eligible patients are clinically diagnosed with MDI or MDL-AII and have failed standardized non-operative management. A diagnostic shoulder arthroscopy is performed to confirm eligibility, followed by intra-operative randomization to the ETAC or ICS surgical procedure. The primary outcome is the disease-specific quality of life questionnaire (Western Ontario Shoulder Instability Index), measured at baseline, 3, 6, 12 and 24 months. Secondary outcomes include shoulder-specific measures (American Shoulder and Elbow Surgeons Score and Constant Score). Other outcomes include recurrent instability, complications and operative time. The outcome measurements will be compared on an intention-to-treat basis, using two-sample independent t-tests to assess statistical significance. A Generalized Estimated Equations (GEE) analysis will determine whether there is an effect over time. DISCUSSION: This ongoing trial has encountered unexpected operational and practical issues, including slow patient enrollment due to high intra-operative exclusion rates. However, the authors have a greater understanding of multi-directional laxity in the shoulder and anticipate the results of this trial will provide the medical community with the best scientific clinical evidence on the efficacy of ETAC compared to open ICS

The Role of Soy in Vegetarian Diets

Soyfoods have long been prized among vegetarians for both their high protein content and versatility. Soybeans differ markedly in macronutrient content from other legumes, being much higher in fat and protein, and lower in carbohydrate. In recent years however, soyfoods and specific soybean constituents, especially isoflavones, have been the subject of an impressive amount of research. Nearly 2,000 soy-related papers are published annually. This research has focused primarily on the benefits that soyfoods may provide independent of their nutrient content. There is particular interest in the role that soyfoods have in reducing risk of heart disease, osteoporosis and certain forms of cancer. However, the estrogen-like effects of isoflavones observed in animal studies have also raised concerns about potential harmful effects of soyfood consumption. This review addresses questions related to soy and chronic disease risk, provides recommendations for optimal intakes, and discusses potential contraindications. As reviewed, the evidence indicates that, with the exception of those individuals allergic to soy protein, soyfoods can play a beneficial role in the diets of vegetarians. Concerns about adverse effects are not supported by the clinical or epidemiologic literature. Based on the soy intake associated with health benefits in the epidemiologic studies and the benefits noted in clinical trials, optimal adult soy intake would appear to be between two and four servings per day

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. Scientific Reports. 6. https://doi.org/10.1038/srep38649S386496Nadrah, P., Planinšek, O. & Gaberšček, M. Stimulus-responsive Mesoporous Silica Particles. J. Mater. Sci. 49, 481–495 (2014).Baeza, A., Colilla, M. & Vallet-Regí, M. Advances in Mesoporous Silica Nanoparticles for Targeted Stimuli-Responsive Drug Delivery. Expert Opin. Drug Deliv. 12, 319–337 (2015).Karimi, M., Mirshekari, H., Aliakbari, M., Zangabad, P. S. & Hamblin, M. R. Smart Mesoporous Silica Nanoparticles for Controlled-Release Drug Delivery. Nanotech. Rev. 5, 195–207 (2016).Aznar, E. et al. Gated Materials for On-Command Release of Guest Molecules. Chem. Rev. 116, 561−718 (2016).Sancenón, F., Pascual, Ll., Oroval, M., Aznar, E. & Martínez-Máñez, R. Gated Silica Mesoporous Materials in Sensing Applications. Chemistry Open. 4, 418–437 (2015).Lu, C.-H., Willner, B. & Willner, I. DNA nanotechnology: From sensing and DNA machines to drug-delivery systems. ACSNano 7, 8320–8332 (2013).Klajn, R., Stoddart, J. F. & Grzybowski, B. A. Nanoparticles Functionalized With Reversible Molecular And Supramolecular Switches. Chem. Soc. Rev. 39, 2203–2237 (2010).Wei, R., Martin, T. G., Rant, U. & Dietz, H. DNA Origami Gatekeepers for Solid-State Nanopores. Angew. Chem. Int. Ed. 51, 4864 4867 (2012).Zhu, C. L., Lu, C. H., Song, X. Y., Yang, H. H. & Wang, X. R. Bioresponsive Controlled Release Using Mesoporous Silica Nanoparticles Capped with Aptamer-Based Molecular Gate. J. Am. Chem. Soc. 133, 1278–1281 (2011).Özalp, V. C., Pinto, A., Nikulina, E., Chulivin, A. & Schäfer, T. In Situ Monitoring of DNA-Aptavalve Gating Function on Mesoporous Silica Nanoparticles. Part. Part. Sys. Charact. 31, 161–167 (2014).Choi, Y. L., Jaworski, J., Seo, M. L., Lee, S. J. & Jung, J. H. Controlled release using mesoporous silica nanoparticles functionalized with 18-crown-6 derivative. J. Mater. Chem. 21, 7882–7885 (2011).Zhang, Z., Wang, F., Balogh, D. & Willner, I. pH-controlled release of substrates from mesoporous SiO2 nanoparticles gated by metal ion-dependent DNAzymes. J. Mater. Chem. B. 2, 4449–4455 (2014).Fu, L. et al. Portable and Quantitative Monitoring of Heavy Metal Ions Using Dnazyme-Capped Mesoporous Silica Nanoparticles with a Glucometer Readout. J. Mater. Chem. B. 1, 6123–6128 (2013).Díez, P. et al. Toward the Design of Smart Delivery Systems Controlled by Integrated Enzyme-Based Biocomputing Ensembles. J. Am. Chem. Soc. 136, 9116–9123 (2014).Tang, D. et al. Low-Cost and Highly Sensitive lmmunosensing Platform for Aflatoxins Using One-Step Competitive Displacement Reaction Mode and Portable Glucometer-Based Detection. Anal. Chem. 86, 11451–11458 (2014).Hou, L., Zhu, C., Wu, X., Chen, G. & Tang, D. Bioresponsive Controlled Release from Mesoporous Silica Nanocontainers with Glucometer Readout. Chem. Commun. 50, 1441–1443 (2014).Chen, Z. et al. 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. Analysis of In Vitro Aptamer Selection Parameters, J. Mol. Evol. 81, 150–161 (2015).Ellington, A. D. & Szostak, J. W. In vitro selection of RNA molecules that bind specific ligands. Nature. 346, 818–822 (1990).Wochner, A. et al. A DNA aptamer with high affinity and specificity for therapeutic anthracyclines. Anal Biochem. 373, 34–42 (2008).Song, K. M., Jeong, E., Jeon, W., Cho, M. & Ban, C. Aptasensor for ampicillin using gold nanoparticle based dual fluorescence-colorimetric methods. Anal. Bioanal. Chem. 402, 2153–2161 (2012).Özalp, V. C. & Schäfer, T. Aptamer-Based Switchable Nanovalves for Stimuli-Responsive Drug Delivery. Chem. Eur. J. 17, 9893–9896 (2011).Stojanovic, M. N., de Prada, P. & Landry, D. W. Aptamer-Based Folding Fluorescent Sensor for Cocaine. J. Am. Chem Soc. 123, 4928–4931 (2001).Wen, Y. et al. DNA-based intelligent logic controlled release systems. Chem. Commun. 48, 8410–8412 (2012).Chen, L. et al. Programmable DNA switch for bioresponsive controlled release. J. Mater. Chem. 21, 13811–13816 (2011).Oroval, M. et al. An aptamer-gated silica mesoporous material for thrombin detection. Chem. Commun. 49, 5480–5482 (2013).Barroso, M., Gallardo, E. & Queiroz, J. A. Bioanalytical methods for the determination of cocaine and metabolites in human biological samples. Bioanalysis. 1, 977–1000 (2009).Phan, H. M., Yoshizuka, K., Murry, D. J. & Perry, P. J. Drug testing in the workplace. Pharmacotherapy. 32, 649–656 (2012).Kidwell, D. A., Blanco, M. A. & P. Smith, F. P. Cocaine detection in a university population by hair analysis and skin swab testing. Forensic Sci. Int. 84, 75–86 (1997).Swensen, J. S. et al. Continuous, Real-Time Monitoring of Cocaine in Undiluted Blood Serum via a Microfluidic, Electrochemical Aptamer-Based Sensor. J. Am. Chem. Soc. 131, 4262–4266 (2009).Cai, Q. et al. Determination of cocaine on banknotes through an aptamer-based electrochemiluminescence biosensor. Anal. Bioanal. Chem. 400, 289–294 (2011).Zou, R. et al. Highly specific triple-fragment aptamer for optical detection of cocaine. RSC Adv. 2, 4636–4638 (2012).Qiu, L. et al. A novel label-free fluorescence aptamer-based sensor method for cocaine detection based on isothermal circular strand-displacement amplification and graphene oxide absorption. New J. Chem. 37, 3998 (2013).Marsal, L. F., Vojkuvka, L., Formentin, P., Pallarés, J. & Ferré-Borrull, J. Fabrication and Optical Characterization of Nanoporous Alumina Films Annealed at Different Temperatures. Optical Mater. 31, 860–864 (2009).Bosker, W. M. & Huestis, M. A. Oral Fluid Testing for Drugs of Abuse. Clinical Chem. 55, 1910–1931 (2009).Kolbrich, E. A. et al. Cozart® RapiScan Oral Fluid Drug Testing System: An Evaluation of Sensitivity, Specificity, and Efficiency for Cocaine Detection Compared with ELISA and GC-MS Following Controlled Cocaine Administration. J. Anal Toxicol. 27, 407–411 (2003).Cooper, G., Wilson, L., Reid, C., Main, L. & Hand, C. Evaluation of the Cozart® RapiScan drug test system for opiates and cocaine in oral fluid. Forensic Sci. Int. 150, 239–243 (2005).Chang, Y. H. et al. Cocaine detection by a mid-infrared waveguide integrated with a microfluidic chip. Lab Chip. 12, 3020–3023 (2012).Walczak, R. et al. Toward Portable Instrumentation for Quantitative Cocaine Detection with Lab-on-a-Paper and Hybrid Optical Readout. Procedia Chem. 1, 999–1002 (2009).Qiu, L. et al. A novel label-free fluorescence aptamer-based sensor method for cocaine detection based on isothermal circular strand-displacement amplification and graphene oxide absorption. New J. Chem. 37, 3998–4003 (2013)

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