The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

PubMed

Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

2017-05-01

The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and demonstrate supersaturation and precipitation of dipyridamole and ketoconazole. We therefore conclude that the GIS has been shown to be a good biopredictive tool to predict in vivo bioperformance of BCS class IIb drugs that can be used to optimize oral formulations. Copyright © 2017. Published by Elsevier B.V.

Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

PubMed

Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

2017-11-21

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique.

PubMed

Khames, Ahmed

2017-11-01

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10-30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE 25 , MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cp max , respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

Computer simulations for bioequivalence trials: Selection of analyte in BCS class II and IV drugs with first-pass metabolism, two metabolic pathways and intestinal efflux transporter.

PubMed

Mangas-Sanjuan, Victor; Navarro-Fontestad, Carmen; García-Arieta, Alfredo; Trocóniz, Iñaki F; Bermejo, Marival

2018-05-30

A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome. A total of 128 scenarios (2 Biopharmaceutics Classification System (BCS) drug types, 2 levels of K M Pgp , in 4 metabolic scenarios at 2 dose levels in 4 quality levels of the drug product) were simulated for BCS class II and IV drugs. Monte Carlo simulations of all bioequivalence studies were performed in NONMEM 7.3. Results showed the parent drug (PD) was the most sensitive analyte for bioequivalence trials in all the studied scenarios. PM and SM revealed less or the same sensitivity to detect differences in pharmaceutical quality as the PD. Another relevant result is that mean point estimate of C max and AUC methodology from Monte Carlo simulations allows to select more accurately the most sensitive analyte compared to the criterion on the percentage of failed or successful BE studies, even for metabolites which frequently show greater variability than PD. Copyright © 2018 Elsevier B.V. All rights reserved.

Is the full potential of the biopharmaceutics classification system reached?

PubMed

Bergström, Christel A S; Andersson, Sara B E; Fagerberg, Jonas H; Ragnarsson, Gert; Lindahl, Anders

2014-06-16

In this paper we analyse how the biopharmaceutics classification system (BCS) has been used to date. A survey of the literature resulted in a compilation of 242 compounds for which BCS classes were reported. Of these, 183 compounds had been reported to belong to one specific BCS class whereas 59 compounds had been assigned to multiple BCS classes in different papers. Interestingly, a majority of the BCS class 2 compounds had fraction absorbed (FA) values >85%, indicating that they were completely absorbed after oral administration. Solubility was computationally predicted at pH 6.8 for BCS class 2 compounds to explore the impact of the pH of the small intestine, where most of the absorption occurs, on the solubility. In addition, the solubilization capacity of lipid aggregates naturally present in the intestine was studied computationally and experimentally for a subset of 12 compounds. It was found that all acidic compounds with FA>85% were completely dissolved in the pH of the small intestine. Further, lipids at the concentration used in fasted state simulated intestinal fluid (FaSSIF) dissolved the complete dose given of the most lipophilic (logD6.5>3) compounds studied. Overall, biorelevant dissolution media (pure buffer of intestinal pH or FaSSIF) identified that for 20 of the 29 BCS class 2 compounds with FA>85% the complete dose given orally would be dissolved. These results indicate that a more relevant pH restriction for acids and/or dissolution medium with lipids present better forecast solubility-limited absorption in vivo than the presently used BCS solubility criterion. The analysis presented herein further strengthens the discussion on the requirement of more physiologically relevant dissolution media for the in vitro solubility classification performed to reach the full potential of the BCS. Copyright © 2013 Elsevier B.V. All rights reserved.

Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

PubMed

Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

2017-02-25

Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Insight into the Development of Dissolution Media for BCS Class II Drugs: A Review from Quality Control and Prediction of In Vivo Performance Perspectives.

PubMed

Wu, Chunnuan; Liu, Yan; He, Zhonggui; Sun, Jin

2016-01-01

To assess in vivo behavior through in vitro method, the dissolution test is mostly used, both for quality control (QC) and for development purpose. In view of the fact that a dissolution test can hardly achieve two goals at the same time, the design of dissolution testing generally varies along with the development stage of drug products and therefore the selection of dissolution media may change with the goals of the dissolution test. To serve the QC purpose, a dissolution medium is designed to provide a sink condition; for development purpose, the dissolution medium is required to simulate the physiological conditions in the gastrointestinal tract as far as possible. In this review, we intended to provide an initial introduction to the various dissolution media applied for QC and formulation development purposes for poorly water soluble drugs. We focused on these methods like addition of cosolvents, surfactants and utilization of biphasic media, applied to provide sink conditions which are difficult to be achieved by simple aqueous buffers for lipophilic drugs, and introduced the development of physiologically relevant media for human and animals like dog and rat with respect to the choice of buffers, bile salts, lipids and so on. In addition, we further discussed the influence of biorelevant dissolution media on the modification of drug Biopharmaceutical Classification System (BCS) classification, especially for BCS class II drugs with low solubility and high permeability, the solubility of which is relatively sensitive to the presence of bile salts and lipids.

Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice.

PubMed

Tehler, Ulrika; Fagerberg, Jonas H; Svensson, Richard; Larhed, Mats; Artursson, Per; Bergström, Christel A S

2013-03-28

Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

PubMed

Zur, Moran; Hanson, Allison S; Dahan, Arik

2014-09-30

While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

BCS and generalized BCS superconductivity in relativistic quantum field theory. II. Numerical calculations

NASA Astrophysics Data System (ADS)

Ohsaku, Tadafumi

2002-08-01

We solve numerically various types of the gap equations developed in the relativistic BCS and generalized BCS framework, presented in part I of this paper. We apply the method for not only the usual solid metal but also other physical systems by using homogeneous fermion gas approximation. We examine the relativistic effects on the thermal properties and the Meissner effect of the BCS and generalized BCS superconductivity of various cases.

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension.

PubMed

Lennernäs, Hans; Abrahamsson, Bertil

2005-03-01

Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.

Disparities in the Initial Local Treatment of Older Women with Early-Stage Breast Cancer: A Population-Based Study.

PubMed

LeMasters, Traci J; Madhavan, Suresh S; Sambamoorthi, Usha; Vyas, Ami M

2017-07-01

Although breast cancer is most prevalent among older women, the majority are diagnosed at an early stage. When diagnosed at an early stage, women have the option of breast-conserving surgery (BCS) plus radiation therapy (RT) or mastectomy for the treatment of early-stage breast cancer (ESBC). Omission of RT when receiving BCS increases the risk for recurrence and poor survival. Yet, a small subset of older women may omit RT after BCS. This study examines the current patterns of local treatment for ESBC among older women. This study conducted a retrospective observational analysis using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked dataset of women age ≥66 diagnosed with stage I-II breast cancer in 2003-2009. SEER-Medicare data was additionally linked with data from the Area Resource File (ARF) to examine the association between area-level healthcare resources and treatment. Two logistic regression models were used to estimate how study factors were associated with receiving (1) BCS versus BCS+RT and (2) Mastectomy versus BCS+RT. A stratified analysis was also conducted among women aged <70 years. Among 45,924 patients, 55% received BCS+RT, 23% received mastectomy, and 22% received BCS only. Women of increasing age, comorbidity, primary care provider visits, stage II disease, and nonwhite race were more likely to have mastectomy or BCS only, than BCS+RT. Women diagnosed in 2004-2006, treated by an oncology surgeon, residing in metro areas, areas of greater education and income, were less likely to receive mastectomy or BCS only, than BCS+RT. While women aged <70 years were more likely to receive BCS+RT, socioeconomic and physician specialties were associated with receiving BCS only. Over half of older women with ESBC initially receive BCS+RT. The likelihood for mastectomy and BCS only increases with age, comorbidity, and vulnerable socio-demographic characteristics. Findings demonstrate continued treatment disparities among certain vulnerable populations.

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules.

PubMed

Dave, Vivek S; Gupta, Deepak; Yu, Monica; Nguyen, Phuong; Varghese Gupta, Sheeba

2017-02-01

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-emulsifying lipid-based formulations.

PubMed

Pestieau, Aude; Krier, Fabrice; Brouwers, Adeline; Streel, Bruno; Evrard, Brigitte

2016-09-20

Fenofibrate, a BCS class II compound, has a low bioavailability especially when taken orally on an empty stomach. The challenge to find a new formulation for providing bioavailability, independent of food, is still ongoing. If the development of a suitable oral delivery formulation of BCS class II compounds is a frequent and great challenge to formulation scientists, the in vitro evaluation of these new formulations is also a great challenge. The purpose of this study was therefore to select an in vitro dissolution test that would be useful and as biorelevant as possible for the development of fenofibrate self-emulsifying lipid-based formulations. In this context, three different fenofibrate formulations, for which in vivo data are available in the literature, were tested using different dissolution tests until we found the one that was the most suitable. As part of this approach, we started with the simplest in vitro dissolution tests and progressed to tests that were increasingly more complex. The first tests were different single phase dissolution tests: a test under sink conditions based on the USP monograph, and different tests under non-sink conditions in non-biorelevant and biorelevant media. Given the inconclusive results obtained with these tests, biphasic dissolution systems were then tested: one with USP apparatus type II alone and another which combined USP apparatus types II and IV. This last combined test seemed the most suitable in vitro dissolution test for the development of the future fenofibrate lipid-based formulations we intend to develop in our own laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

[Trade-offs in the development of various dosage form (overview)].

PubMed

Uchida, Takahiro

2015-01-01

In this symposium we focused on trade-offs which might occur in the process of development of many types of formulation and corresponding dissolution methods. Firstly, we focused on a solubility-permeability trade-off in the case of micelle with surfactant or molecular complex with CyD. The micelle would be successful in increasing drug solubility, however it rather decreased permeability of model drug progesterone (Biopharmaceutics Classfication System (BCS) Class II) as an overall flux. Secondly in order to reduce bitterness of branched chain amino acid (BCAA), increasing particle sizes of each amino acid crystals involved in formulation was effective since the release rate of amino acid was restricted efficiently. Thirdly, in the case of injection of paclitaxel (BCS Class II)formulation, the drug was adsorbed to albumin. Thereby the risk of allergy was dramatically decreased compared to the case when non-ionic surfactant was used as an additive. Fourth, anticancer drug was incorporated into the internal (core) phase of an orally disintegrating tablet (ODT), this is also merit to avoid exposure of the drug to a nursing person or individual working person in manufacturing process. Fifth, the convenient syringe type kit pharmaceutical preparation for administration of total parenteral nutrition (TPN) to avoid incompatibility and its risk management effect was briefly discussed. Finally, the risk of an additive such as alcohol for a preterm infant was described.

Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.

PubMed

Fong, Sophia Yui Kau; Ibisogly, Asiye; Bauer-Brandl, Annette

2015-12-30

The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

PubMed

Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

2014-02-01

Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers.

PubMed

Abalos, Ivana S; Rodríguez, Yanina I; Lozano, Verónica; Cereseto, Marina; Mussini, Maria V; Spinetto, Marta E; Chiale, Carlos; Pesce, Guido

2012-09-01

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group). Since biperiden permeability was higher than those obtained for high permeability drugs, we classified it as a BCS class I compound. On the other hand, as no differences were obtained for permeability values when apical to basolateral and basolateral to apical fluxes were studied, this drug cannot act as a substrate of efflux transporters. As a consequence of our results, we suggest that the widely used antiparkinsonian drug, biperiden, should be candidate for a waiver of in vivo bioequivalence studies. Copyright © 2012 Elsevier B.V. All rights reserved.

pH-Dependent solubility and permeability criteria for provisional biopharmaceutics classification (BCS and BDDCS) in early drug discovery.

PubMed

Varma, Manthena V; Gardner, Iain; Steyn, Stefanus J; Nkansah, Paul; Rotter, Charles J; Whitney-Pickett, Carrie; Zhang, Hui; Di, Li; Cram, Michael; Fenner, Katherine S; El-Kattan, Ayman F

2012-05-07

The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a basis for predicting the oral absorption of drugs. These concepts have been extended in the Biopharmaceutics Drug Disposition Classification System (BDDCS) to explain the potential mechanism of drug clearance and understand the effects of uptake and efflux transporters on absorption, distribution, metabolism, and elimination. The objective of present work is to establish criteria for provisional biopharmaceutics classification using pH-dependent passive permeability and aqueous solubility data generated from high throughput screening methodologies in drug discovery settings. The apparent permeability across monolayers of clonal cell line of Madin-Darby canine kidney cells, selected for low endogenous efflux transporter expression, was measured for a set of 105 drugs, with known BCS and BDDCS class. The permeability at apical pH 6.5 for acidic drugs and at pH 7.4 for nonacidic drugs showed a good correlation with the fraction absorbed in human (Fa). Receiver operating characteristic (ROC) curve analysis was utilized to define the permeability class boundary. At permeability ≥ 5 × 10(-6) cm/s, the accuracy of predicting Fa of ≥ 0.90 was 87%. Also, this cutoff showed more than 80% sensitivity and specificity in predicting the literature permeability classes (BCS), and the metabolism classes (BDDCS). The equilibrium solubility of a subset of 49 drugs was measured in pH 1.2 medium, pH 6.5 phosphate buffer, and in FaSSIF medium (pH 6.5). Although dose was not considered, good concordance of the measured solubility with BCS and BDDCS solubility class was achieved, when solubility at pH 1.2 was used for acidic compounds and FaSSIF solubility was used for basic, neutral, and zwitterionic compounds. Using a cutoff of 200 μg/mL, the data set suggested a 93% sensitivity and 86% specificity in predicting both the BCS and BDDCS solubility classes. In conclusion, this study identified pH-dependent permeability and solubility criteria that can be used to assign provisional biopharmaceutics class at early stage of the drug discovery process. Additionally, such a classification system will enable discovery scientists to assess the potential limiting factors to oral absorption, as well as help predict the drug disposition mechanisms and potential drug-drug interactions.

Effect of gastric pH on the pharmacokinetics of a BCS class II compound in dogs: utilization of an artificial stomach and duodenum dissolution model and GastroPlus,™ simulations to predict absorption.

PubMed

Bhattachar, Shobha N; Perkins, Everett J; Tan, Jeffrey S; Burns, Lee J

2011-11-01

Dogs are one of the most commonly used non-rodent species in toxicology studies and are known to have basal stomach pH ranging from 2 to 7 in the fasted state. Thus absorption and resulting plasma exposure of weakly basic compounds administered as crystalline suspensions to dogs are often variable. LY2157299 is a potent and selective transforming growth factor (TGF)-beta receptor type 1 kinase (TGF-βRI) inhibitor that displayed variable absorption in early dog studies. This molecule is a weakly basic Biopharmaceutics Classification System (BCS)Class II compound, and depends on the rate and extent of dissolution to drive oral absorption. An artificial stomach and duodenum (ASD) dissolution model was utilized to evaluate potential effect of gastric pH on the absorption of suspension and buffered solution formulations. GastroPlus™ was also employed to predict the magnitude of gastric pH changes on LY2157299 absorption. The ASD experiments demonstrated that administration of a buffered acidic solution could improve the potential for absorption by normalizing gastric pH and enabling supersaturation in the duodenum. GastroPlus™ modeling suggested that direct modulation of gastric pH could lead to marked changes in bioavailability. Pharmacokinetic experiments were conducted in dogs to evaluate the effect of gastric pH modification on plasma exposure. The data were qualitatively consistent with the predictions. Copyright © 2011 Wiley-Liss, Inc.

Regional-dependent intestinal permeability and BCS classification: elucidation of pH-related complexity in rats using pseudoephedrine.

PubMed

Fairstein, Moran; Swissa, Rotem; Dahan, Arik

2013-04-01

Based on its lower Log P value relative to metoprolol, a marker for the low/high-permeability (P(eff)) class boundary, pseudoephedrine was provisionally classified as BCS low-permeability compound. On the other hand, following oral administration, pseudoephedrine fraction dose absorbed (F(abs)) and systemic bioavailability approaches 100%. This represents a challenge to the generally recognized P(eff)-F(abs) correlation. The purpose of this study was to elucidate the underlying mechanisms behind the confusion in pseudoephedrine's BCS classification. Pseudoephedrine's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Pseudoephedrine was found to be unequivocally a high-solubility compound. All of the permeability studies revealed similar phenomenon; at any given intestinal segment/pH, the permeability of metoprolol was higher than that of pseudoephedrine, however, as the intestinal region becomes progressively distal, and the pH gradually increases, pseudoephedrine's permeability rises above that of metoprolol in the former segment. This unique permeability pattern likely explains pseudoephedrine's complete absorption. In conclusion, pseudoephedrine is a BCS Class I compound; no discrepancy between P(eff) and F(abs) is involved in its absorption. Rather, it reflects the complexity behind P(eff) when considering the whole of the intestine. We propose to allow high-permeability classification to drugs with P(eff) that matches/exceeds the low/high class benchmark anywhere throughout the intestinal tract and not restricted necessarily to the jejunum.

[A report of two Chinese familial Budd-Chiari syndrome].

PubMed

Feng, B; Xu, K; Jiang, H; Fu, W; Li, H; Guo, M; Liu, X; Wang, Z

2000-09-01

To investigate the etiology of two Chinese familial Budd-Chiari syndrome (BCS). Four patients with familial BCS (from A and B families), and the other 41 family members were detected by angiography, ultrasound Dopler, etiology analysis and Factor V Leiden (FvL) mutation analysis. Four BCS patients were proved by angiography, 2 by ultra sound Dopler in family A. Ten members in family A were varicosis in low extremeties. FvL mutation was detected in 4 of 6 patients and 2 normal family members. A II(2), A III(7, 11, 15,) B II(10) and B III(5) had FvL mutation. The FvL mutations were compatible with Mendel hereditary law. FvL mutation may be one of main risk factors and varicosis in low extremeties may be another risk factors for familial BCS.

Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence.

PubMed

García-Arieta, Alfredo

2014-12-18

The aim of the present paper is to illustrate the impact that excipients may have on the bioavailability of drugs and to review existing US-FDA, WHO and EMA regulatory guidelines on this topic. The first examples illustrate that small amounts of sorbitol (7, 50 or 60mg) affect the bioavailability of risperidone, a class I drug, oral solution, in contrast to what is stated in the US-FDA guidance. Another example suggests, in contrast to what is stated in the US-FDA BCS biowaivers guideline, that a small amount of sodium lauryl sulphate (SLS) (3.64mg) affects the bioavailability of risperidone tablets, although the reference product also includes SLS in an amount within the normal range for that type of dosage form. These factors are considered sufficient to ensure that excipients do not affect bioavailability according to the WHO guideline. The alternative criterion, defined in the WHO guideline and used in the FIP BCS biowaivers monographs, that asserts that excipients present in generic products of the ICH countries do not affect bioavailability if used in normal amounts, is shown to be incorrect with an example of alendronate (a class III drug) tablets, where 4mg of SLS increases bioavailability more than 5-fold, although a generic product in the USA contains SLS. Finally, another example illustrates that a 2mg difference in SLS may affect bioavailability of a generic product of a class II drug, even if SLS is contained in the comparator product, and in all cases its amount was within the normal range. Therefore, waivers of in vivo bioequivalence studies (e.g., BCS biowaivers, waivers of certain dosage forms in solution at the time of administration and variations in the excipient composition) should be assessed more cautiously. Copyright © 2014 Elsevier B.V. All rights reserved.

Biowaiver monographs for immediate release solid oral dosage forms: ibuprofen.

PubMed

Potthast, H; Dressman, J B; Junginger, H E; Midha, K K; Oeser, H; Shah, V P; Vogelpoel, H; Barends, D M

2005-10-01

Literature data are reviewed on the properties of ibuprofen related to the biopharmaceutics classification system (BCS). Ibuprofen was assessed to be a BCS class II drug. Differences in composition and/or manufacturing procedures were reported to have an effect on the rate, but not the extent of absorption; such differences are likely to be detectable by comparative in vitro dissolution tests. Also in view of its therapeutic use, its wide therapeutic index and uncomplicated pharmacokinetic properties, a biowaiver for immediate release (IR) ibuprofen solid oral drug products is scientifically justified, provided that the test product contains only those excipients reported in this paper in their usual amounts, the dosage form is rapidly dissolving (85% in 30 min or less) in buffer pH 6.8 and the test product also exhibits similar dissolution profiles to the reference product in buffer pH 1.2, 4.5, and 6.8. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Survival in stage I-III breast cancer patients by surgical treatment in a publicly funded health care system.

PubMed

Fisher, S; Gao, H; Yasui, Y; Dabbs, K; Winget, M

2015-06-01

Recent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada. Surgically treated stage I-III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan-Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received. A total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13-1.48; stage III HR = 1.74, 95% CI 1.24-2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09-1.76; stage III HR = 1.79, 95% CI 1.21-2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival. Stage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and appropriate. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs - a case study with valsartan.

PubMed

Chella, Naveen; Tadikonda, Ramarao

2015-06-01

Solid dispersion (SD) technique is a promising strategy to improve the solubility and dissolution of BCS class II drugs. However, only few products are marketed till today based on SD technology due to poor flow properties and stability. The present work was intended to solve these problems by using combination approach, melt dispersion and surface adsorption technologies. The main aim of the present work is to improve the absorption in the stomach (at lower pH) where the absorption window exists for the drug by improving the dissolution, resulting in the enhancement of oral bioavailability of poorly soluble, weakly acidic drug with pH dependant solubility, i.e. valsartan. Melt dispersion granules were prepared in different ratios using different carriers (Gelucire 50/13, PEG 8000 and Pluronic F-68) and lactose as an adsorbent. Similarly, physical mixtures were also prepared at corresponding ratios. The prepared dispersion granules and physical mixtures were characterized by FTIR, DSC and in vitro dissolution studies. DSC studies revealed reduction in the crystallinity with a possibility of presence of amorphous character of drug in the dispersion granules. From dissolution studies, valsartan Gelucire dispersion (GSD4; 1:4 ratio) showed complete drug release in 30 min against the plain drug which showed only 11.31% of drug release in 30 min. Pharmacokinetic studies of optimized formulation in male Wistar rats showed 2.65-fold higher bioavailability and 1.47-fold higher Cmax compared to pure drug. The melt dispersion technology has the potential to improve dissolution and the bioavailability of BCS class II drugs.

Effect of induced body condition score differences on physiological response, productive and reproductive performance of Malpura ewes kept in a hot, semi-arid environment.

PubMed

Sejian, V; Maurya, V P; Naqvi, S M K; Kumar, D; Joshi, A

2010-04-01

This study was undertaken to study the influence of induced body condition score (BCS) differences on physiological response, productive and reproductive performance of Malpura ewes to optimise BCS for these ewes for maximising production making it economically viable. The study was conducted for a period of 1 year using thirty healthy Malpura ewes (2-4 year old). The animals were randomly divided and different BCS was induced within three groups named Group I (BCS 2.5; n = 10), Group II (BCS 3.0-3.5; n = 10) and Group III (BCS 4.0; n = 10). The parameters included in the study were allometric measurements, physiological response, wool yield and reproductive performance. BCS had a significant influence on allometric measurements, respiration rate and different reproductive parameters studied, while wool production differed significantly during spring and non-significantly during autumn. The results revealed that the reproductive performance of Malpura ewes with a BCS of 3.0-3.5 was better in comparison with the groups with lower and higher BCS. It may be concluded from this study that an active management of breeding sheep flock to achieve a BCS of 3.0-3.5 may prove to result in an economically viable return from these flocks.

Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

PubMed

Stavchansky, Salomon

2008-06-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

The Bellevue Classification System: nursing's voice upon the library shelves*†

PubMed Central

Mages, Keith C

2011-01-01

This article examines the inspiration, construction, and meaning of the Bellevue Classification System (BCS), created during the 1930s for use in the Bellevue School of Nursing Library. Nursing instructor Ann Doyle, with assistance from librarian Mary Casamajor, designed the BCS after consulting with library leaders and examining leading contemporary classification systems, including the Dewey Decimal Classification and Library of Congress, Ballard, and National Health Library classification systems. A close textual reading of the classes, subclasses, and subdivisions of these classification systems against those of the resulting BCS, reveals Doyle's belief that the BCS was created not only to organize the literature, but also to promote the burgeoning intellectualism and professionalism of early twentieth-century American nursing. PMID:21243054

Transfer Behavior of the Weakly Acidic BCS Class II Drug Valsartan from the Stomach to the Small Intestine During Fasted and Fed States.

PubMed

Hamed, Rania; Alnadi, Sabreen Hasan

2018-05-07

The objective of this study was to investigate the transfer behavior of the weakly acidic BCS class II drug valsartan from the stomach to the small intestine during fasted and fed states. An in vitro transfer model previously introduced by Kostewicz et al. (J Pharm Pharmacol 56(1):43-51, 2004) based on a syringe pump and a USP paddle apparatus was used to determine the concentration profiles of valsartan in the small intestine. Donor phases of simulated gastric fluid during fasted (FaSSGF) and fed (FeSSGF) states were used to predisperse Diovan® tablets (160 mg valsartan). The initial concentrations of valsartan in FaSSGF and FeSSGF were 6.2 and 91.8%, respectively. Valsartan dispersions were then transferred to acceptor phases that simulate intestinal fluid and cover the physiological properties (pH, buffer capacity, and ionic strength) of the gastrointestinal fluid at a flow rate of 2 mL/min. The pH measurements were reported at time intervals corresponded to those of the transfer experiments to investigate the effect of percent dissolved of valsartan in the donor phase on lowering the pH of the acceptor phases. The f2 similarity test was used to compare the concentration profiles in the acceptor phases. In fasted state, the concentration of valsartan in the acceptor phases ranged between 33.1 and 89.4% after 240 min. Whereas in fed state, valsartan was fully dissolved in all acceptor phases within a range of 94.5-104.9% after 240 min. Therefore, the transfer model provides a useful screen for the concentrations of valsartan in the small intestine during fasted and fed states.

Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning.

PubMed

Marano, Stefania; Barker, Susan Anne; Raimi-Abraham, Bahijja Tolulope; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Craig, Duncan Q M

2016-06-01

Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a Weakly Basic BCS Class II Drug.

PubMed

Hamed, Rania; Awadallah, Areeg; Sunoqrot, Suhair; Tarawneh, Ola; Nazzal, Sami; AlBaraghthi, Tamadur; Al Sayyad, Jihan; Abbas, Aiman

2016-04-01

The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1-2591.4 μg/mL within the pH range 1.2-5.0) and low solubility at high pH (5.8-51.9 μg/mL within the pH range 6.5-7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8-98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

Solubilization of the poorly water soluble drug, telmisartan, using supercritical anti-solvent (SAS) process.

PubMed

Park, Junsung; Cho, Wonkyung; Cha, Kwang-Ho; Ahn, Junhyun; Han, Kang; Hwang, Sung-Joo

2013-01-30

Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability. Because of its unique characteristics, the supercritical anti-solvent (SAS) process was used to BCS class II drug in a variety of ways including micronization, amorphization and solid dispersion. Solid dispersions were prepared using hydroxypropylmethylcellulose/polyvinylpyrrolidone (HPMC/PVP) at 1:0.5, 1:1, and 1:2 weight ratios of drug to polymer, and pure telmisartan was also treated using the SAS process. Processed samples were characterized for morphology, particle size, crystallinity, solubility, dissolution rate and polymorphic stability. After the SAS process, all samples were converted to the amorphous form and were confirmed to be hundreds nm in size. Solubility and dissolution rate were increased compared to the raw material. Solubility tended to increase with increases in the amount of polymer used. However, unlike the solubility results, the dissolution rate decreased with increases in polymer concentration due to gel layer formation of the polymer. Processed pure telmisartan showed the best drug release even though it had lower solubility compared to other solid dispersions; however, because there were no stabilizers in processed pure telmisartan, it recrystallized after 1 month under severe conditions, while the other solid dispersion samples remained amorphous form. We conclude that after controlling the formulation of solid dispersion, the SAS process could be a promising approach for improving the solubility and dissolution rate of telmisartan. Copyright © 2012 Elsevier B.V. All rights reserved.

Facilitators of Survivorship Care Among Underserved Breast Cancer Survivors: a Qualitative Study.

PubMed

Ustjanauskas, Amy E; Quinn, Gwendolyn P; Pan, Tonya M; Rivera, Maria; Vázquez-Otero, Coralia; Ung, Danielle; Roetzheim, Richard G; Laronga, Christine; Johnson, Kenneth; Norton, Marilyn; Carrizosa, Claudia; Muñoz, Dariana; Goldenstein, Marissa; Nuhaily, Sumayah; Wells, Kristen J

2017-12-01

Research investigating facilitators of survivorship care among underserved breast cancer survivors (BCS) is sparse. This study aimed to explore facilitators of survivorship care among underserved BCS within the first 5 years following chemotherapy, radiation, or surgery for breast cancer. In-depth interviews were conducted, using a semi-structured interview guide, with underserved BCS exploring survivorship care experiences. Content analysis of the verbatim transcripts was applied, and results were summarized according to themes related to facilitators of breast cancer survivorship care. Interviews were conducted with 25 BCS. Eight main themes were identified: coordination of care; positive perceptions of health care providers; communication between patient and health care providers; financial and insurance facilitators; information, classes, and programs provided; assistance provided by organizations and health care professionals; transportation facilitators; and job flexibility. This study provides a comprehensive look at facilitators of survivorship care among underserved BCS. BCS endorsed several facilitators of their survivorship care, mainly at the interpersonal, organizational, and societal level. This study adds to the research literature on catalysts of care among underserved BCS. Results from this study are currently being used to inform a patient navigation intervention to facilitate care among this population.

Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

PubMed

Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

2013-02-01

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches.

PubMed

Lozoya-Agullo, Isabel; Zur, Moran; Wolk, Omri; Beig, Avital; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival; Dahan, Arik

2015-03-01

Intestinal drug permeability has been recognized as a critical determinant of the fraction dose absorbed, with direct influence on bioavailability, bioequivalence and biowaiver. The purpose of this research was to compare intestinal permeability values obtained by two different intestinal rat perfusion methods: the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop) rat perfusion method. A list of 15 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was constructed. We assessed the rat intestinal permeability of these 15 model drugs in both SPIP and the Doluisio methods, and evaluated the correlation between them. We then evaluated the ability of each of these methods to predict the fraction dose absorbed (Fabs) in humans, and to assign the correct BCS permeability class membership. Excellent correlation was obtained between the two experimental methods (r(2)=0.93). An excellent correlation was also shown between literature Fabs values and the predictions made by both rat perfusion techniques. Similar BCS permeability class membership was designated by literature data and by both SPIP and Doluisio methods for all compounds. In conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method are both equally useful for obtaining intestinal permeability values that can be used for Fabs prediction and BCS classification. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of automatic body condition scoring using a low-cost 3-dimensional Kinect camera.

PubMed

Spoliansky, Roii; Edan, Yael; Parmet, Yisrael; Halachmi, Ilan

2016-09-01

Body condition scoring (BCS) is a farm-management tool for estimating dairy cows' energy reserves. Today, BCS is performed manually by experts. This paper presents a 3-dimensional algorithm that provides a topographical understanding of the cow's body to estimate BCS. An automatic BCS system consisting of a Kinect camera (Microsoft Corp., Redmond, WA) triggered by a passive infrared motion detector was designed and implemented. Image processing and regression algorithms were developed and included the following steps: (1) image restoration, the removal of noise; (2) object recognition and separation, identification and separation of the cows; (3) movie and image selection, selection of movies and frames that include the relevant data; (4) image rotation, alignment of the cow parallel to the x-axis; and (5) image cropping and normalization, removal of irrelevant data, setting the image size to 150×200 pixels, and normalizing image values. All steps were performed automatically, including image selection and classification. Fourteen individual features per cow, derived from the cows' topography, were automatically extracted from the movies and from the farm's herd-management records. These features appear to be measurable in a commercial farm. Manual BCS was performed by a trained expert and compared with the output of the training set. A regression model was developed, correlating the features with the manual BCS references. Data were acquired for 4 d, resulting in a database of 422 movies of 101 cows. Movies containing cows' back ends were automatically selected (389 movies). The data were divided into a training set of 81 cows and a test set of 20 cows; both sets included the identical full range of BCS classes. Accuracy tests gave a mean absolute error of 0.26, median absolute error of 0.19, and coefficient of determination of 0.75, with 100% correct classification within 1 step and 91% correct classification within a half step for BCS classes. Results indicated good repeatability, with all standard deviations under 0.33. The algorithm is independent of the background and requires 10 cows for training with approximately 30 movies of 4 s each. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet.

PubMed

Cheng, Ching-Ling; Yu, Lawrence X; Lee, Hwei-Ling; Yang, Chyun-Yu; Lue, Chang-Sha; Chou, Chen-Hsi

2004-07-01

The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-infinity) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

Improving the dissolution and bioavailability of 6-mercaptopurine via co-crystallization with isonicotinamide.

PubMed

Wang, Jian-Rong; Yu, Xueping; Zhou, Chun; Lin, Yunfei; Chen, Chen; Pan, Guoyu; Mei, Xuefeng

2015-03-01

6-Mercaptopurine (6-MP) is a clinically important antitumor drug. The commercially available form was provided as monohydrate and belongs to BCS class II category. Co-crystallization screening by reaction crystallization method (RCM) and monitored by powder X-ray diffraction led to the discovery of a new co-crystal formed between 6-MP and isonicotinamide (co-crystal 1). Co-crystal 1 was thoroughly characterized by X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analysis. Noticeably, the in vitro and in vivo studies revealed that co-crystal 1 possesses improved dissolution rate and superior bioavailability on animal model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bacterial cellulose synthesis mechanism of facultative anaerobe Enterobacter sp. FY-07.

PubMed

Ji, Kaihua; Wang, Wei; Zeng, Bing; Chen, Sibin; Zhao, Qianqian; Chen, Yueqing; Li, Guoqiang; Ma, Ting

2016-02-25

Enterobacter sp. FY-07 can produce bacterial cellulose (BC) under aerobic and anaerobic conditions. Three potential BC synthesis gene clusters (bcsI, bcsII and bcsIII) of Enterobacter sp. FY-07 have been predicted using genome sequencing and comparative genome analysis, in which bcsIII was confirmed as the main contributor to BC synthesis by gene knockout and functional reconstitution methods. Protein homology, gene arrangement and gene constitution analysis indicated that bcsIII had high identity to the bcsI operon of Enterobacter sp. 638; however, its arrangement and composition were same as those of BC synthesizing operon of G. xylinum ATCC53582 except for the flanking sequences. According to the BC biosynthesizing process, oxygen is not directly involved in the reactions of BC synthesis, however, energy is required to activate intermediate metabolites and synthesize the activator, c-di-GMP. Comparative transcriptome and metabolite quantitative analysis demonstrated that under anaerobic conditions genes involved in the TCA cycle were downregulated, however, genes in the nitrate reduction and gluconeogenesis pathways were upregulated, especially, genes in three pyruvate metabolism pathways. These results suggested that Enterobacter sp. FY-07 could produce energy efficiently under anaerobic conditions to meet the requirement of BC biosynthesis.

Bacterial cellulose synthesis mechanism of facultative anaerobe Enterobacter sp. FY-07

PubMed Central

Ji, Kaihua; Wang, Wei; Zeng, Bing; Chen, Sibin; Zhao, Qianqian; Chen, Yueqing; Li, Guoqiang; Ma, Ting

2016-01-01

Enterobacter sp. FY-07 can produce bacterial cellulose (BC) under aerobic and anaerobic conditions. Three potential BC synthesis gene clusters (bcsI, bcsII and bcsIII) of Enterobacter sp. FY-07 have been predicted using genome sequencing and comparative genome analysis, in which bcsIII was confirmed as the main contributor to BC synthesis by gene knockout and functional reconstitution methods. Protein homology, gene arrangement and gene constitution analysis indicated that bcsIII had high identity to the bcsI operon of Enterobacter sp. 638; however, its arrangement and composition were same as those of BC synthesizing operon of G. xylinum ATCC53582 except for the flanking sequences. According to the BC biosynthesizing process, oxygen is not directly involved in the reactions of BC synthesis, however, energy is required to activate intermediate metabolites and synthesize the activator, c-di-GMP. Comparative transcriptome and metabolite quantitative analysis demonstrated that under anaerobic conditions genes involved in the TCA cycle were downregulated, however, genes in the nitrate reduction and gluconeogenesis pathways were upregulated, especially, genes in three pyruvate metabolism pathways. These results suggested that Enterobacter sp. FY-07 could produce energy efficiently under anaerobic conditions to meet the requirement of BC biosynthesis. PMID:26911736

Chemical Modification and Structure-property Relationships of Acrylic and Ionomeric Thermoplastic Elastomer Gels

NASA Astrophysics Data System (ADS)

Vargantwar, Pruthesh Hariharrao

Block copolymers (BCs) have remained at the forefront of materials research due to their versatility in applications ranging from hot-melt/pressure-sensitive adhesives and impact modifiers to compatibilizing agents and vibration-dampening/nanotemplating media. Of particular interest are macromolecules composed of two or more chemically dissimilar blocks covalently linked together to form triblock or pentablock copolymers. If the blocks are sufficiently incompatible and the copolymer behaves as a thermoplastic elastomer, the molecules can spontaneously self-assemble to form nanostructured materials that exhibit shape memory due to the formation of a supramolecular network. The BCs of these types are termed as conventional. When BCs contain blocks having ionic moieties such as sulfonic acid groups, they are termed as block ionomers. Designing new systems based on either conventional or ionic BCs, characterizing their structure-property relationships and later using them as electroacive polymers form the essential objectives of this work. Electroactive polymers (EAPs) exhibit electromechanical actuation when stimulated by an external electric field. In the first part of this work, it is shown that BCs resolve some of the outstanding problems presently encountered in the design of two different classes of EAP actuators: dielectric elastomers (DEs) and ionic polymer metal composites (IPMCs). All-acrylic triblock copolymer gels used as DEs actuate with high efficacy without any requirement of mechanical prestrain and, thus, eliminate the need for bulky and heavy hardware essential with prestrained dielectric actuators, as well as material problems associated with stress relaxation. The dependence of actuation behavior on gel morphology as evaluated from mechanical and microstructure studies is observed. In the case of IPMCs, ionic BCs employed in this study greatly facilitate processing compared to other contenders such as NafionRTM, which is commonly used in this class of EAPs. The unique copolymer investigated here (i) retains its mechanical integrity when highly solvated by polar solvents, (ii) demonstrates a high degree of actuation when tested in a cantilever configuration, and (iii) avoids the shortcomings of back-relaxation/overshoot within the testing conditions when used in combination with an appropriate solvent. In the second part of this work, two chemical strategies to design midblock sulfonated block ionomers are explored. In one case, selective sulfonation of the midblocks in triblock copolymers is achieved via a dioxane:sulfur trioxide chemistry, while in the other acetyl sulfate is used for the same purpose. Excellent control on the degree of sulfonation (DOS) is achieved. The block ionomers swell in different solvents while retaining their mechanical integrity. They show disorder-order, order-order, and order-reduced order morphological transitions as DOS varies. These transitions in morphologies are reflected in their thermal behavior as well. The microstructures show periodicity, which is, again, a function of DOS. The transitions are explained in terms of the molar volume expansion and volume densification of the blocks on sulfonation. The ionic levels, morphology and periodicity in microstructure are important for applications such as actuators, sensors and fuel cell membranes. The ability to tune these aspects in the ionomers designed in this work make them potential candidates for these applications.

Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors.

PubMed

Wang, Shushu; Zhang, Yi; Yang, Xinhua; Fan, Linjun; Qi, Xiaowei; Chen, Qingqiu; Jiang, Jun

2013-07-24

Breast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients' quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT. Ninety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining. The residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2. Three types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.

Purely in silico BCS classification: science based quality standards for the world's drugs.

PubMed

Dahan, Arik; Wolk, Omri; Kim, Young Hoon; Ramachandran, Chandrasekharan; Crippen, Gordon M; Takagi, Toshihide; Bermejo, Marival; Amidon, Gordon L

2013-11-04

BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs according to the BCS, using in silico methods. Three different in silico methods were examined: the well-established group contribution (CLogP) and atom contribution (ALogP) methods, and a new method based solely on the molecular formula and element contribution (KLogP). Metoprolol was used as the benchmark for the low/high permeability class boundary. Solubility was estimated in silico using a thermodynamic equation that relies on the partition coefficient and melting point. The validity of each method was affirmed by comparison to reference data and literature. We then used each method to provisionally classify the orally administered, IR drug products found in the WHO Model list of Essential Medicines, and the top-selling oral drug products in the United States (US), Great Britain (GB), Spain (ES), Israel (IL), Japan (JP), and South Korea (KR). A combined list of 363 drugs was compiled from the various lists, and 257 drugs were classified using the different in silico permeability methods and literature solubility data, as well as BDDCS classification. Lastly, we calculated the solubility values for 185 drugs from the combined set using in silico approach. Permeability classification with the different in silico methods was correct for 69-72.4% of the 29 reference drugs with known human jejunal permeability, and for 84.6-92.9% of the 14 FDA reference drugs in the set. The correlations (r(2)) between experimental log P values of 154 drugs and their CLogP, ALogP and KLogP were 0.97, 0.82 and 0.71, respectively. The different in silico permeability methods produced comparable results: 30-34% of the US, GB, ES and IL top selling drugs were class 1, 27-36.4% were class 2, 22-25.5% were class 3, and 5.46-14% were class 4 drugs, while ∼8% could not be classified. The WHO list included significantly less class 1 and more class 3 drugs in comparison to the countries' lists, probably due to differences in commonly used drugs in developing vs industrial countries. BDDCS classified more drugs as class 1 compared to in silico BCS, likely due to the more lax benchmark for metabolism (70%), in comparison to the strict permeability benchmark (metoprolol). For 185 out of the 363 drugs, in silico solubility values were calculated, and successfully matched the literature solubility data. In conclusion, relatively simple in silico methods can be used to estimate both permeability and solubility. While CLogP produced the best correlation to experimental values, even KLogP, the most simplified in silico method that is based on molecular formula with no knowledge of molecular structure, produced comparable BCS classification to the sophisticated methods. This KLogP, when combined with a mean melting point and estimated dose, can be used to provisionally classify potential drugs from just molecular formula, even before synthesis. 49-59% of the world's top-selling drugs are highly soluble (class 1 and class 3), and are therefore candidates for waivers of in vivo bioequivalence studies. For these drugs, the replacement of expensive human studies with affordable in vitro dissolution tests would ensure their bioequivalence, and encourage the development and availability of generic drug products in both industrial and developing countries.

Preparation and evaluation of cilnidipine microemulsion

PubMed Central

Tandel, Hemal; Raval, Krunal; Nayani, Anil; Upadhay, Manish

2012-01-01

Cilnidipine, a calcium channel blocker having neuroprotective action and BCS Class II drug, hence formulating in Microemulsion will increase solubility, absorption and bioavailability. The formulation was prepared using titration method by tocotrienol, tween 20 and transcutol HP as oil, surfactant and co-surfactant and characterized for dilutability, dye solubility, assay (98.39±0.06), pH (6.6±1.5), Viscosity (98±1.0 cps) and Conductivity (0.2±0.09 μS/cm). The formulation was optimized on basis of percentage transmittance (99.269±0.23 at 700 nm), Globule size (13.31±4.3 nm) and zeta potential (–11.4±2.3 mV). Cilnidipine microemulsion was found to be stable for 3 months. PMID:23066184

Low-viscosity hydroxypropylcellulose (HPC) grades SL and SSL: versatile pharmaceutical polymers for dissolution enhancement, controlled release, and pharmaceutical processing.

PubMed

Sarode, Ashish; Wang, Peng; Cote, Catherine; Worthen, David R

2013-03-01

Hydroxypropylcellulose (HPC)-SL and -SSL, low-viscosity hydroxypropylcellulose polymers, are versatile pharmaceutical excipients. The utility of HPC polymers was assessed for both dissolution enhancement and sustained release of pharmaceutical drugs using various processing techniques. The BCS class II drugs carbamazepine (CBZ), hydrochlorthiazide, and phenytoin (PHT) were hot melt mixed (HMM) with various polymers. PHT formulations produced by solvent evaporation (SE) and ball milling (BM) were prepared using HPC-SSL. HMM formulations of BCS class I chlorpheniramine maleate (CPM) were prepared using HPC-SL and -SSL. These solid dispersions (SDs) manufactured using different processes were evaluated for amorphous transformation and dissolution characteristics. Drug degradation because of HMM processing was also assessed. Amorphous conversion using HMM could be achieved only for relatively low-melting CBZ and CPM. SE and BM did not produce amorphous SDs of PHT using HPC-SSL. Chemical stability of all the drugs was maintained using HPC during the HMM process. Dissolution enhancement was observed in HPC-based HMMs and compared well to other polymers. The dissolution enhancement of PHT was in the order of SE>BM>HMM>physical mixtures, as compared to the pure drug, perhaps due to more intimate mixing that occurred during SE and BM than in HMM. Dissolution of CPM could be significantly sustained in simulated gastric and intestinal fluids using HPC polymers. These studies revealed that low-viscosity HPC-SL and -SSL can be employed to produce chemically stable SDs of poorly as well as highly water-soluble drugs using various pharmaceutical processes in order to control drug dissolution.

Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

PubMed

Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-12-01

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Cellulose Microfibril Formation by Surface-Tethered Cellulose Synthase Enzymes.

PubMed

Basu, Snehasish; Omadjela, Okako; Gaddes, David; Tadigadapa, Srinivas; Zimmer, Jochen; Catchmark, Jeffrey M

2016-02-23

Cellulose microfibrils are pseudocrystalline arrays of cellulose chains that are synthesized by cellulose synthases. The enzymes are organized into large membrane-embedded complexes in which each enzyme likely synthesizes and secretes a β-(1→4) glucan. The relationship between the organization of the enzymes in these complexes and cellulose crystallization has not been explored. To better understand this relationship, we used atomic force microscopy to visualize cellulose microfibril formation from nickel-film-immobilized bacterial cellulose synthase enzymes (BcsA-Bs), which in standard solution only form amorphous cellulose from monomeric BcsA-B complexes. Fourier transform infrared spectroscopy and X-ray diffraction techniques show that surface-tethered BcsA-Bs synthesize highly crystalline cellulose II in the presence of UDP-Glc, the allosteric activator cyclic-di-GMP, as well as magnesium. The cellulose II cross section/diameter and the crystal size and crystallinity depend on the surface density of tethered enzymes as well as the overall concentration of substrates. Our results provide the correlation between cellulose microfibril formation and the spatial organization of cellulose synthases.

The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters-an Update.

PubMed

Zhang, Wenpeng; Li, Yanyan; Zou, Peng; Wu, Man; Zhang, Zhenqing; Zhang, Tao

2016-07-01

Accumulating evidence from the last decade has shown that many pharmaceutical excipients are not pharmacologically inert but instead have effects on metabolic enzymes and/or drug transporters. Hence, the absorption, distribution, metabolism, and elimination (ADME) of active pharmaceutical ingredients (APIs) may be altered due to the modulation of their metabolism and transport by excipients. The impact of excipients is a potential concern for Biopharmaceutics Classification System (BCS)-based biowaivers, particularly as the BCS-based biowaivers have been extended to class 3 drugs in certain dosage forms. The presence of different excipients or varying amounts of excipients between formulations may result in bio-inequivalence. The excipient impact may lead to significant variations in clinical outcomes as well. The aim of this paper is to review the recent findings of excipient effects on gastrointestinal (GI) absorption, focusing on their interactions with the metabolic enzymes and transporters in the GI tract. A wide range of commonly used excipients such as binders, diluents, fillers, solvents, and surfactants are discussed here. We summarized the reported effects of those excipients on GI tract phase I and phase II enzymes, uptake and efflux transporters, and relevant clinical significance. This information can enhance our understanding of excipient influence on drug absorption and is useful in designing pharmacokinetic studies and evaluating the resultant data.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam.

PubMed

Petruševska, Marija; Berglez, Sandra; Krisch, Igor; Legen, Igor; Megušar, Klara; Peternel, Luka; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Mehta, Mehul; Polli, James E; Shah, Vinod P; Dressman, Jennifer

2015-09-01

Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open literature. On the basis of the overall evidence, it appears unlikely that a BCS-based biowaiver approach for levetiracetam IR solid oral dosage forms formulated with established excipients would expose patients to undue risks. Thus, the BCS-based biowaiver approach procedure is recommended for IR solid oral dosage form containing levetiracetam, provided the excipients in the formulation are also present in products that have been approved in countries belonging to or associated with the International Committee on Harmonization and are used in their usual quantities, and provided the dissolution profiles of the test and reference product comply with the current requirements for BCS-based biowaivers. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Comparison of different pairing fluctuation approaches to BCS-BEC crossover

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levin, Kathryn; Chen Qijin; Zhejiang Institute of Modern Physics and Department of Physics, Zhejiang University, Hangzhou, Zhejiang 310027

2010-02-15

The subject of BCS-Bose-Einstein condensation (BEC) crossover is particularly exciting because of its realization in ultracold atomic Fermi gases and its possible relevance to high temperature superconductors. In this paper we review the body of theoretical work on this subject, which represents a natural extension of the seminal papers by Leggett and by Nozieres and Schmitt-Rink (NSR). The former addressed only the ground state, now known as the 'BCS-Leggett' wave-function, and the key contributions of the latter pertain to calculations of the superfluid transition temperature T{sub c}. These two papers have given rise to two main and, importantly, distinct, theoreticalmore » schools in the BCS-BEC crossover literature. The first of these extends the BCS-Leggett ground state to finite temperature and the second extends the NSR scheme away from T{sub c} both in the superfluid and normal phases. It is now rather widely accepted that these extensions of NSR produce a different ground state than that first introduced by Leggett. This observation provides a central motivation for the present paper which seeks to clarify the distinctions in the two approaches. Our analysis shows how the NSR-based approach views the bosonic contributions more completely but treats the fermions as 'quasi-free'. By contrast, the BCS-Leggett based approach treats the fermionic contributions more completely but treats the bosons as 'quasi-free'. In a related fashion, the NSR-based schemes approach the crossover between BCS and BEC by starting from the BEC limit and the BCS-Leggett based scheme approaches this crossover by starting from the BCS limit. Ultimately, one would like to combine these two schemes. There are, however, many difficult problems to surmount in any attempt to bridge the gap in the two theory classes. In this paper we review the strengths and weaknesses of both approaches. The flexibility of the BCS-Leggett based approach and its ease of handling make it widely used in T=0 applications, although the NSR-based schemes tend to be widely used at T{ne}0. To reach a full understanding, it is important in the future to invest effort in investigating in more detail the T=0 aspects of NSR-based theory and at the same time the T{ne}0 aspects of BCS-Leggett theory.« less

Childhood socioeconomic position and adult mental wellbeing: Evidence from four British birth cohort studies.

PubMed

Wood, Natasha; Bann, David; Hardy, Rebecca; Gale, Catharine; Goodman, Alissa; Crawford, Claire; Stafford, Mai

2017-01-01

There is much evidence showing that childhood socioeconomic position is associated with physical health in adulthood; however existing evidence on how early life disadvantage is associated with adult mental wellbeing is inconsistent. This paper investigated whether childhood socioeconomic position (SEP) is associated with adult mental wellbeing and to what extent any association is explained by adult SEP using harmonised data from four British birth cohort studies. The sample comprised 20,717 participants with mental wellbeing data in the Hertfordshire Cohort Study (HCS), the MRC National Survey of Health and Development (NSHD), the National Child Development Study (NCDS), and the British Cohort Study (BCS70). Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) scores at age 73 (HCS), 60-64 (NSHD), 50 (NCDS), or 42 (BCS70) were used. Harmonised socioeconomic position (Registrar General's Social Classification) was ascertained in childhood (age 10/11) and adulthood (age 42/43). Associations between childhood SEP, adult SEP, and wellbeing were tested using linear regression and multi-group structural equation models. More advantaged father's social class was associated with better adult mental wellbeing in the BCS70 and the NCDS. This association was independent of adult SEP in the BCS70 but fully mediated by adult SEP in the NCDS. There was no evidence of an association between father's social class and adult mental wellbeing in the HCS or the NSHD. Socioeconomic conditions in childhood are directly and indirectly, through adult socioeconomic pathways, associated with adult mental wellbeing, but findings from these harmonised data suggest this association may depend on cohort or age.

Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development

PubMed Central

Wolk, Omri; Agbaria, Riad; Dahan, Arik

2014-01-01

The main objective of this work was to investigate in-silico predictions of physicochemical properties, in order to guide oral drug development by provisional biopharmaceutics classification system (BCS). Four in-silico methods were used to estimate LogP: group contribution (CLogP) using two different software programs, atom contribution (ALogP), and element contribution (KLogP). The correlations (r2) of CLogP, ALogP and KLogP versus measured LogP data were 0.97, 0.82, and 0.71, respectively. The classification of drugs with reported intestinal permeability in humans was correct for 64.3%–72.4% of the 29 drugs on the dataset, and for 81.82%–90.91% of the 22 drugs that are passively absorbed using the different in-silico algorithms. Similar permeability classification was obtained with the various in-silico methods. The in-silico calculations, along with experimental melting points, were then incorporated into a thermodynamic equation for solubility estimations that largely matched the reference solubility values. It was revealed that the effect of melting point on the solubility is minor compared to the partition coefficient, and an average melting point (162.7°C) could replace the experimental values, with similar results. The in-silico methods classified 20.76% (±3.07%) as Class 1, 41.51% (±3.32%) as Class 2, 30.49% (±4.47%) as Class 3, and 6.27% (±4.39%) as Class 4. In conclusion, in-silico methods can be used for BCS classification of drugs in early development, from merely their molecular formula and without foreknowledge of their chemical structure, which will allow for the improved selection, engineering, and developability of candidates. These in-silico methods could enhance success rates, reduce costs, and accelerate oral drug products development. PMID:25284986

Childhood socioeconomic position and adult mental wellbeing: Evidence from four British birth cohort studies

PubMed Central

Bann, David; Hardy, Rebecca; Gale, Catharine; Goodman, Alissa; Crawford, Claire; Stafford, Mai

2017-01-01

Background There is much evidence showing that childhood socioeconomic position is associated with physical health in adulthood; however existing evidence on how early life disadvantage is associated with adult mental wellbeing is inconsistent. This paper investigated whether childhood socioeconomic position (SEP) is associated with adult mental wellbeing and to what extent any association is explained by adult SEP using harmonised data from four British birth cohort studies. Methods The sample comprised 20,717 participants with mental wellbeing data in the Hertfordshire Cohort Study (HCS), the MRC National Survey of Health and Development (NSHD), the National Child Development Study (NCDS), and the British Cohort Study (BCS70). Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) scores at age 73 (HCS), 60–64 (NSHD), 50 (NCDS), or 42 (BCS70) were used. Harmonised socioeconomic position (Registrar General’s Social Classification) was ascertained in childhood (age 10/11) and adulthood (age 42/43). Associations between childhood SEP, adult SEP, and wellbeing were tested using linear regression and multi-group structural equation models. Results More advantaged father’s social class was associated with better adult mental wellbeing in the BCS70 and the NCDS. This association was independent of adult SEP in the BCS70 but fully mediated by adult SEP in the NCDS. There was no evidence of an association between father’s social class and adult mental wellbeing in the HCS or the NSHD. Conclusions Socioeconomic conditions in childhood are directly and indirectly, through adult socioeconomic pathways, associated with adult mental wellbeing, but findings from these harmonised data suggest this association may depend on cohort or age. PMID:29069091

Application of laboratory prepared and commercially available biochars to adsorption of cadmium, copper and zinc ions from water.

PubMed

Bogusz, Aleksandra; Oleszczuk, Patryk; Dobrowolski, Ryszard

2015-11-01

The goal of the presented work was the evaluation and comparison of two biochars (produced from Sida hermaphrodita - BCSH/laboratory produced and from wheatstraw - BCS/commercial available) to adsorb heavy metal ions (Cd(II), Cu(II) and Zn(II)) from water. Kinetics of the sorption as well as sorption isotherms, the influence of solution pH and interfering ions were investigated. Different physico-chemical properties of biochars had the great influence on adsorption capacity. The greater adsorption efficiency was observed for BCSH than for BCS in the case of all investigated metals. The adsorption efficiency of BCSH was correlated with higher content of carbon and oxygen, what is equal with higher content of polar-groups on the BCSH surface e.g., -COOH. Furthermore, the molar ratio of O/C as well as polarity index (which was higher for BCSH) was also important parameters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

PubMed

Teixeira, M C; Carbone, C; Souto, E B

2017-10-01

Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

Solid dispersions, part II: new strategies in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

PubMed

Bikiaris, Dimitrios N

2011-12-01

The absorption of poorly water-soluble drugs, when presented in the crystalline state to the gastrointestinal tract, is typically dissolution rate-limited, and according to BCS these drugs belong mainly to class II. Both dissolution kinetics and solubility are particle size dependent. Nowadays, various techniques are available to the pharmaceutical industry for dissolution rate enhancement of such drugs. Among such techniques, nanosuspensions and drug formulation in solid dispersions are those with the highest interest. This review discusses strategies undertaken over the last 10 years, which have been applied for the dissolution enhancement of poorly water-soluble drugs; such processes include melt mixing, electrospinning, microwave irradiation and the use of inorganic nanoparticles. Many problems in this field still need to be solved, mainly the use of toxic solvents, and for this reason the use of innovative new procedures and materials will increase over the coming years. Melt mixing remains extremely promising for the preparation of SDs and will probably become the most used method in the future for the preparation of solid drug dispersions.

Advantageous Solubility-Permeability Interplay When Using Amorphous Solid Dispersion (ASD) Formulation for the BCS Class IV P-gp Substrate Rifaximin: Simultaneous Increase of Both the Solubility and the Permeability.

PubMed

Beig, Avital; Fine-Shamir, Noa; Lindley, David; Miller, Jonathan M; Dahan, Arik

2017-05-01

Rifaximin is a BCS class IV (low-solubility, low-permeability) drug and also a P-gp substrate. The aims of this work were to assess the efficiency of different rifaximin amorphous solid dispersion (ASDs) formulations in achieving and maintaining supersaturation and to investigate the consequent solubility-permeability interplay. Spray-dried rifaximin ASDs were prepared with different hydrophilic polymers and their ability to achieve and maintain supersaturation was assessed. Then, rifaximin's apparent intestinal permeability was investigated as a function of increasing supersaturation both in vitro using the parallel artificial membrane permeability assay (PAMPA) and in vivo using the single-pass rat intestinal perfusion (SPIP) model. The efficiency of the different ASDs to achieve and maintain supersaturation of rifaximin was found to be highly polymer dependent, and the copovidone/HPC-SL formulation was found to be superior to the other two, allowing supersaturation of 200× that of the crystalline solubility for 20 h. In vitro, rifaximin flux was increased and the apparent permeability was constant as a function of increasing supersaturation level. In vivo, on the other hand, absorption rate coefficient (k a ) was first constant as a function of increasing supersaturation, but at 250×, the crystalline solubility k a was doubled, similar to the k a in the presence of the strong P-gp inhibitor GF120918. In conclusion, a new and favorable nature of solubility-permeability interplay was revealed in this work: delivering high supersaturation level of the BCS class IV drug rifaximin via ASD, thereby saturating the drugs' P-gp-mediated efflux transport, led to the favorable unique win-win situation, where both the solubility and the permeability increased simultaneously.

Severe fatigue after treatment of ductal carcinoma in situ: A comparison with age-matched breast cancer survivors and healthy controls.

PubMed

Abrahams, H J G; Smits, L; Lugt, M de; Roos, W K de; Kamm, Y; Heins, M J; Verhagen, C A H H V M; Gielissen, M F M; Knoop, H

2017-02-01

Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients. 89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength. 23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue. The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of two bioelectrical impedance analysis instruments for determining body composition in adolescent girls

PubMed Central

Nichols, J.; Going, S.; Loftin, M.; Stewart, D.; Nowicki, E.; Pickrel, J.

2007-01-01

The purpose of this study was to compare fat-free mass (FFM) and percent body fat determined by two bio-electrical impedance analysis (BIA) instruments against criterion estimates determined by dual-energy x-ray absorptiometry (DXA) in a multi-racial/ethnic sample of adolescent girls. BIA was assessed in 151 girls (n=51 African-American; n=45 Hispanic; n=55 Caucasian; age 12.2 ± 1.2 yr) using the RJL Quantum II and the American Weights and Measures Body-Comp Scale (BCS). Percent body fat determined by BIA was significantly related to that determined by DXA (R2=0.87, SEE=2.8% for RJL vs DXA, P<0.0001; R2=0.71, SEE=4.4% for BCS vs DXA, P<0.0001). The agreement between DXA and BIA for FFM was also significant (R2=0.91, SEE=0.03 kg for RJL, P <0.0001; R2=0.79, SEE=0.04 kg for BCS, P <0.0001). The BCS overestimated FFM by 2.7 kg (P<0.0001) and underestimated percent body fat by over 4% (P<0.001). There were no differences in percent body fat between DXA and the RJL, and although the RJL significantly overestimated FFM, the absolute difference was <1 kg. Within each ethnic group, the RJL instrument more closely estimated FFM and percent body fat than did the BCS. Although both BIA instruments compared favorably with DXA, the RJL had better stability and accuracy than the BCS, for both the total sample and for the three ethnic groups. Considering its relatively low cost and minimal time required for technical training, BIA is a useful and appropriate technique for assessing body composition in adolescent girls. PMID:17607326

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

PubMed

Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, Dirk W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

2018-07-01

Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Chitosan-palmitic acid based polymeric micelles as promising carrier for circumventing pharmacokinetic and drug delivery concerns of tamoxifen.

PubMed

Thotakura, Nagarani; Dadarwal, Mukesh; Kumar, Rajendra; Singh, Bhupinder; Sharma, Gajanand; Kumar, Pramod; Katare, Om Prakash; Raza, Kaisar

2017-09-01

Being a BCS class II drug and a good substrate for microsomal enzymes, tamoxifen (TAM) offers a scope for research owing to poor aqueous solubility and compromised bioavailability. The present study designs a novel copolymer derived from palmitic acid and chitosan, and evaluate the derived TAM-loaded micelles for various delivery attributes. The nanometric micellar carriers not only substantially loaded the drug, but also controlled the rate of release of TAM. The designed nanocarrier significantly enhanced the cytotoxicity of TAM on MCF-7 cancer cells. The developed system was designed for intravenous route and was observed to be substantially haemo-compatible with an enhancement of approx. 5 times in AUC vis-a-vis plain drug. The findings employing new polymer-based carrier are promising in nature for the better delivery of similar drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigating the Discriminatory Power of BCS-Biowaiver in Vitro Methodology to Detect Bioavailability Differences between Immediate Release Products Containing a Class I Drug.

PubMed

Colón-Useche, Sarin; González-Álvarez, Isabel; Mangas-Sanjuan, Victor; González-Álvarez, Marta; Pastoriza, Pilar; Molina-Martínez, Irene; Bermejo, Marival; García-Arieta, Alfredo

2015-09-08

The purpose of this work is to investigate the discriminatory power of the Biopharmaceutics Classification System (BCS)-biowaiver in vitro methodology, i.e., to investigate if a BCS-biowaiver approach would have detected the Cmax differences observed between two zolpidem tablets and to identify the cause of the in vivo difference. Several dissolution conditions were tested with three zolpidem formulations: the reference (Stilnox), a bioequivalent formulation (BE), and a nonbioequivalent formulation (N-BE). Zolpidem is highly soluble at pH 1.2, 4.5, and 6.8. Its permeability in Caco-2 cells is higher than that of metoprolol and its transport mechanism is passive diffusion. None of the excipients (alone or in combination) showed any effect on permeability. All formulations dissolved more than 85% in 15 min in the paddle apparatus at 50 rpm in all dissolution media. However, at 30 rpm the nonbioequivalent formulation exhibited a slower dissolution rate. A slower gastric emptying rate was also observed in rats for the nonbioequivalent formulation. A slower disintegration and dissolution or a delay in gastric emptying might explain the Cmax infra-bioavailability for a highly permeable drug with short half-life. The BCS-biowaiver approach would have declared bioequivalence, although the in vivo study was not conclusive but detected a 14% mean difference in Cmax that precluded the bioequivalence demonstration. Nonetheless, these findings suggest that a slower dissolution rate is more discriminatory and that rotation speeds higher than 50 rpm should not be used in BCS-biowaivers, even if a coning effect occurs.

Fibrinolysis status in the Budd-Chiari syndrome in China.

PubMed

Ke, Zhang; Hao, Xu; Ning, Wei; Zu, Mao-heng; Fun, Yu-fei

2015-10-01

Pathogenesis and clinical characteristics of the Budd-Chiari syndrome (BCS) in Asia are somewhat different from the ones observed in Western countries. Obstruction of the inferior vena cava (IVC) or of the hepatic veins is caused to a greater extent by membranous webs than by thrombosis. Impaired fibrinolysis has been found in European patients with BCS, but its status in Chinese patients with this condition is still unknown. To explore the characteristics of fibrinolysis in BCS patients in this country, we measured the euglobulin lysis time (ELT) for overall fibrinolysis and the plasma levels of five fibrinolytic components in 65 Chinese patients with BCS and 43 healthy controls. In patients, ELTs were slightly shorter than in controls (mean, 293 vs. 357 min, P < 0.02), tissue type plasminogen activator levels were higher than in controls (mean, 239 vs. 185 pg/ml, P < 0.01), and plasminogen activator inhibitor 1 levels were lower than in controls (mean, 1.43 vs. 1.73 ng/ml, P < 0.001). To explore BCS in more detail, we subgrouped the cases according to age, type of venous occlusion, Child-Pugh score, and thrombosis. As a result of this analysis, we found that young patients (age <30 years) had a longer ELT (mean, 440 min) than the older patient groups (30 ≤ age ≤ 44, 45 ≤ age ≤ 54, age>54 years; mean ELT = 242, 198, and 289 min, respectively, all P < 0.05). The independent hepatic vein occlusion subgroup showed a longer ELT (mean, 367 min) than the combined hepatic vein and IVC or the independent IVC occlusion subgroup (mean ELT = 233 and 260 min, both P < 0.05). ELT did not show significant differences between Child-Pugh class A and B subgroups (mean, 267 vs. 333 min, P > 0.05). ELT in the subgroup without thrombosis was shorter than in controls (mean, 288 vs. 358 min, P < 0.05), and in the subgroup with thrombosis, it was also slightly shorter than in controls, without reaching statistical significance (mean, 306 vs. 358 min, P > 0.05). By and large, overall fibrinolytic potential was slightly increased in Chinese patients with BCS in this study, but fibrinolysis differed according to its baseline characteristics. Compared with the one seen in BCS patients from Western countries, BCS in China exhibits certain special changes in fibrinolysis and we were able to explain some of these changes.

A functional approach to the body condition assessment of lactating donkeys as a tool for welfare evaluation

PubMed Central

Raspa, Federica; Giribaldi, Marzia; Barbero, Raffaella; Bergagna, Stefania; Antoniazzi, Sara; Mc Lean, Amy K.; Minero, Michela; Cavallarin, Laura

2017-01-01

Background The breeding of lactating donkeys is increasing in Western Europe; with it the evaluation of body condition is growing in importance since it is considered a key principle for their welfare. However, assessment of body condition is a complex task, since several factors are involved. The aim of the present study is to investigate which animal-based indicators are the most reliable to describe the body condition of lactating donkeys. For this purpose, new animal-based indicators, which are easy to measure in field conditions (including body measurements, fatty neck score (FNS), dental score), are recorded and their relationship with BCS (a proxy measure for overall adiposity) was assessed. The ones that reveal an association with the BCS are included in an integrated principal component analysis to understand which are the most related to BCS. Methods Fifty-three healthy lactating donkeys of various breeds, including 7 Martina Franca, 10 Ragusano, 2 Romagnolo and 34 crossbreeds, were evaluated. The animal-based indicators that were recorded were: length (OP, olecranon tuber-pinbone and SH, shoulder-hip), heart girth (HG), abdominal circumference (AC), neck length (NL), neck height (NH) and neck thickness (NT) at 0.50 and neck circumference (NC) at 0.25, 0.50 and 0.75, body condition score (BCS) and fatty neck score (FNS). The owners’ evaluation of the BCS was also considered. A dental assessment was performed and the month of lactation and age of each animal was recorded. Results No correlation was found between BCS and the other morphometric body measurements. On the contrary the FNS was correlated with the morphometric measurements of the neck (positive correlation to 0.50 NH and 0.50 NT, 0.50 NC, 0.75 mean NC, and negative correlation to the mean NC:NH and mean NC:NT, 0.50 NC:NT and 0.50 NC:NH ratios). A significant inverse relationship was identified between BCS and dental score. A Principal Component analysis (PCA) separated the BCS classes on the first principal component (PC1). PC1 revealed a meaningful positive correlation between the BCS and the neck measurements (NT, NH and FNS), with high positive loadings, while a negative correlation was found for dental abnormalities. The owners’ evaluation of BCS was different from the expert evaluator’ assessment, since they tended to give higher score that was slightly but significantly correlated to AC. Discussion A new scoring system, called Fatty Neck Score (FNS), has been proposed for the judgement of the adiposity status of donkey neck. The results suggest that caregivers might use the proposed animal based indicators (BCS, FNS and dental scores) together as a tool for the evaluation of the body condition of lactating donkeys. Our findings highlight that caregivers need to be trained in order to be able to properly record these indicators. Ultimately use of these indicators may help to improve the welfare of lactating donkeys. PMID:28367363

Solubility behavior and biopharmaceutical classification of novel high-solubility ciprofloxacin and norfloxacin pharmaceutical derivatives.

PubMed

Breda, Susana A; Jimenez-Kairuz, Alvaro F; Manzo, Ruben H; Olivera, María E

2009-04-17

The hydrochlorides of the 1:3 aluminum:norfloxacin and aluminum:ciprofloxacin complexes were characterized according to the Biopharmaceutics Classification System (BCS) premises in comparison with their parent compounds. The pH-solubility profiles of the complexes were experimentally determined at 25 and 37 degrees C in the range of pH 1-8 and compared to that of uncomplexed norfloxacin and ciprofloxacin. Both complexes are clearly more soluble than the antibiotics themselves, even at the lowest solubility pHs. The increase in solubility was ascribed to the species controlling solubility, which were analyzed in the solid phases at equilibrium at selected pHs. Additionally, permeability was set as low, based on data reported in the scientific literature regarding oral bioavailability, intestinal and cell cultures permeabilities and also considering the influence of stoichiometric amounts of aluminum. The complexes fulfill the BCS criterion to be classified as class 3 compounds (high solubility/low permeability). Instead, the active pharmaceutical ingredients (APIs) currently used in solid dosage forms, norfloxacin and ciprofloxacin hydrochloride, proved to be BCS class 4 (low solubility/low permeability). The solubility improvement turns the complexes as potential biowaiver candidates from the scientific point of view and may be a good way for developing more dose-efficient formulations. An immediate release tablet showing very rapid dissolution was obtained. Its dissolution profile was compared to that of the commercial ciprofloxacin hydrochloride tablets allowing to dissolution of the complete dose at a critical pH such as 6.8.

The low/high BCS permeability class boundary: physicochemical comparison of metoprolol and labetalol.

PubMed

Zur, Moran; Gasparini, Marisa; Wolk, Omri; Amidon, Gordon L; Dahan, Arik

2014-05-05

Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability class boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability class reference drug. Labetalol's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5-7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol-buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitro PAMPA permeability assay. The results of the in vivo perfusion studies in rats lay between the two contradictory in vitro studies; metoprolol was shown to have moderately higher rat intestinal permeability than labetalol. Theoretical distribution of the ionic species of the drugs was in corroboration with the experimental in vitro and the in vivo data. We propose three characteristics that the optimal permeability class reference drug should exhibit: (1) fraction dose absorbed in the range of 90%; (2) the optimal marker drug should be absorbed largely via passive transcellular permeability, with no/negligible carrier-mediated active intestinal transport (influx or efflux); and (3) the optimal marker drug should preferably be nonionizable. The data presented in this paper demonstrate that neither metoprolol nor labetalol can be regarded as optimal low/high-permeability class boundary standard. While metoprolol is too conservative due to its complete absorption, labetalol has been shown to be a substrate for P-gp-mediated efflux transport, and both drugs exhibit significant segmental-dependent permeability along the gastrointestinal tract. Nevertheless, the use of metoprolol as the marker compound does not carry a risk of bioinequivalence: Peff value similar to or higher than metoprolol safely indicates high-permeability classification. On the other hand, a more careful data analysis is needed if labetalol is used as the reference compound.

Soft gelatin capsules (softgels).

PubMed

Gullapalli, Rampurna Prasad

2010-10-01

It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds.

Hydrophobin-nanofibrillated cellulose stabilized emulsions for encapsulation and release of BCS class II drugs.

PubMed

Paukkonen, Heli; Ukkonen, Anni; Szilvay, Geza; Yliperttula, Marjo; Laaksonen, Timo

2017-03-30

The purpose of this study was to construct biopolymer-based oil-in-water emulsion formulations for encapsulation and release of poorly water soluble model compounds naproxen and ibuprofen. Class II hydrophobin protein HFBII from Trichoderma reesei was used as a surfactant to stabilize the oil/water interfaces of the emulsion droplets in the continuous aqueous phase. Nanofibrillated cellulose (NFC) was used as a viscosity modifier to further stabilize the emulsions and encapsulate protein coated oil droplets in NFC fiber network. The potential of both native and oxidized NFC were studied for this purpose. Various emulsion formulations were prepared and the abilities of different formulations to control the drug release rate of naproxen and ibuprofen, used as model compounds, were evaluated. The optimal formulation for sustained drug release consisted of 0.01% of drug, 0.1% HFBII, 0.15% oxidized NFC, 10% soybean oil and 90% water phase. By comparison, the use of native NFC in combination with HFBII resulted in an immediate drug release for both of the compounds. The results indicate that these NFC originated biopolymers are suitable for pharmaceutical emulsion formulations. The native and oxidized NFC grades can be used as emulsion stabilizers in sustained and immediate drug release applications. Furthermore, stabilization of the emulsions was achieved with low concentrations of both HFBII and NFC, which may be an advantage when compared to surfactant concentrations of conventional excipients traditionally used in pharmaceutical emulsion formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Cooper-pair and Bose-Einstein condensations in two dimensions: A critical analysis based on the Nozieres and Schmitt-Rink formalism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tokumitu, A.; Miyake, K.; Yamada, K.

1993-05-01

The crossover between the Cooper-pair condensation and the Bose-Einstein condensation of di-electronic'' molecules in two-dimensional superconductors is investigated in detail on the basis of the Nozieres and Schmitt-Rink formalism. It is shown that temperature dependence of the chemical potential [mu] so calculated is classified into two classes as decreasing temperatures; i.e., class (a) where [mu] approaches the point of Bose-Einstein condensation of two-dimensional ideal Bose gas of di-electronic'' molecules, and class (b) where [mu] diverges positively along the line of BCS-type mean-field pair condensation. This feature is rather universal irrespective of strength [ital V] of the attractive interaction of themore » [ital s]-wave type. While the former class (a) has been found by Schmitt-Rink, Varma, and Ruckenstein, existence of the latter class (b) is recognized here. In the case where [ital V] is fixed, class (a) is realized for electron number density [ital N] smaller than [ital N][sub cr], which is an increasing function of [ital V], and class (b) is realized for [ital N] larger than [ital N][sub cr]. If [ital N][much gt][ital N][sub cr] in particular, there exists a regime, where the Fermi-liquid-like description is valid, between the BCS-type mean-field transition temperature and the Fermi temperature. In the situation where [ital V] is changed with [ital N] being fixed, low-temperature states for the strong-coupling case belong to class (a) while those for the weak-coupling case belong to class (b). Therefore, with decreasing [ital V], the chemical potential [mu]([ital T]), at temperatures far below the Fermi temperature, shows a discontinuous jump at [ital V]=[ital V][sub cr]([ital N]) corresponding to the transition from class (a) to (b).« less

Quality of preimplantation embryos recovered in vivo from dairy cows in relation to their body condition.

PubMed

Makarevich, A V; Stádník, L; Kubovičová, E; Hegedüšová, Z; Holásek, R; Louda, F; Beran, J; Nejdlová, M

2016-06-01

This study examined the impact of cow body condition on the quality of bovine preimplantation embryos. The embryos (n = 107) were flushed from dairy cows and classified according to a five-point scale body condition score (BCS2 n = 17; BCS3 n = 31; BCS4 n = 11) on the 7th day after insemination and then analyzed for development, dead cell index (DCI), cell number and actin cytoskeleton quality. The highest embryo recovery rate (P < 0.05) was recorded in the BCS3 group and the lowest in the BCS4 group. More transferable (morula, blastocyst) embryos were obtained from the BCS4 cows (79%), compared with the BCS2 (64%) or BCS3 (63%) animals. However, cell numbers were higher in the BCS2 and BCS3 groups (P < 0.05) compared with the BCS4 embryos. Conversely, the DCI was lowest in the BCS2 (3.88%; P < 0.05) and highest in the BCS4 (6.56%) embryos. The proportion of embryos with the best actin quality (grade I) was higher in the BCS2 and BCS3 cows compared with the BCS4 group. Almost 25% of all embryos showed fragmented morphology and a higher DCI (5.65%) than normal morulas (1.76%). More fragmented embryos were revealed in the BCS2 (28.6%) and BCS4 (31.25%) groups, and less (19.15%) in the BCS3 group. The cell numbers in such embryos were lower in the BCS4 (22.57) than in the BCS2 (46.25) or BCS3 (42.4) groups. In conclusion, the body condition of dairy cows affects the quality of preimplantation embryos. A BCS over 3.0 resulted in a higher incidence of poor (fragmented) embryos.

75 FR 27170 - Energy Conservation Program for Consumer Products: Determination Concerning the Potential for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-14

... issue a final rule determining whether to issue efficiency standards for battery chargers (BCs) and EPSs... Standards for Non- Class A External Power Supplies AGENCY: Office of Energy Efficiency and Renewable Energy... Office of Energy Efficiency and Renewable Energy's Web site at http://www.eere.energy.gov/buildings...

Influence of birthweight on childhood balance: Evidence from two British birth cohorts.

PubMed

Okuda, Paola Matiko Martins; Swardfager, Walter; Ploubidis, George B; Pangelinan, Melissa; Cogo-Moreira, Hugo

2018-01-26

Birthweight is an important predictor of various fundamental aspects of childhood health and development. To examine the impact of birthweight on childhood balance performance classification and verify if this is replicable and consistent in different populations. Prospective birth cohort study. To describe heterogeneity in balance skills, latent class analyses were conducted separately with data from the 1958 National Child Development Study - NCDS (n = 12,778), and the 1970 British Cohort Study - BCS (n = 12,115). Four balance tasks for NCDS and five balance tasks for BCS. Birthweight was assessed as a predictor of balance skills. In both cohorts, two latent classes (good and poor balance skills) were identified. In both cohorts, higher birthweight was associated with a higher likelihood of having good balance skills. Boys were less likely to have good balance compared to girls. The results establish the reproducibility and consistency of the effect of birthweight on balance skills and point to early intervention for individuals with lower birthweight to mitigate the impact of motor impairment. Copyright © 2018 Elsevier B.V. All rights reserved.

Layer-specific gene expression in epileptogenic type II focal cortical dysplasia: normal-looking neurons reveal the presence of a hidden laminar organization

PubMed Central

2014-01-01

Background Type II focal cortical dysplasias (FCDs) are malformations of cortical development characterised by the disorganisation of the normal neocortical structure and the presence of dysmorphic neurons (DNs) and balloon cells (BCs). The pathogenesis of FCDs has not yet been clearly established, although a number of histopathological patterns and molecular findings suggest that they may be due to abnormal neuronal and glial proliferation and migration processes. In order to gain further insights into cortical layering disruption and investigate the origin of DNs and BCs, we used in situ RNA hybridisation of human surgical specimens with a neuropathologically definite diagnosis of Type IIa/b FCD and a panel of layer-specific genes (LSGs) whose expression covers all cortical layers. We also used anti-phospho-S6 ribosomal protein antibody to investigate mTOR pathway hyperactivation. Results LSGs were expressed in both normal and abnormal cells (BCs and DNs) but their distribution was different. Normal-looking neurons, which were visibly reduced in the core of the lesion, were apparently located in the appropriate cortical laminae thus indicating a partial laminar organisation. On the contrary, DNs and BCs, labelled with anti-phospho-S6 ribosomal protein antibody, were spread throughout the cortex without any apparent rule and showed a highly variable LSG expression pattern. Moreover, LSGs did not reveal any differences between Type IIa and IIb FCD. Conclusion These findings suggest the existence of hidden cortical lamination involving normal-looking neurons, which retain their ability to migrate correctly in the cortex, unlike DNs which, in addition to their morphological abnormalities and mTOR hyperactivation, show an altered migratory pattern. Taken together these data suggest that an external or environmental hit affecting selected precursor cells during the very early stages of cortical development may disrupt normal cortical development. PMID:24735483

Evaluation of the use of partition coefficients and molecular surface properties as predictors of drug absorption: a provisional biopharmaceutical classification of the list of national essential medicines of Pakistan

PubMed Central

Shawahna, R.; Rahman, NU.

2011-01-01

Background and the purpose of the study Partition coefficients (log D and log P) and molecular surface area (PSA) are potential predictors of the intestinal permeability of drugs. The aim of this investigation was to evaluate and compare these intestinal permeability indicators. Methods Aqueous solubility data were obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability data were predicted based on log P, log D at pH 6.0 (log D6.0), and PSA. Results Metoprolol's log P, log D6.0, and a PSA of <65 Å correctly predicted 55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P, log D6.0 and PSA correctly predicted 54.2%, 64.4% and 61% of permeability classes, respectively. Log D6.0 correlated well (81%) with Caco-2 permeability (Papp). Of the list of national essential medicines, 135 orally administered drugs were classified into biopharmaceutical classification system (BCS). Of these, 57 (42.2%), 28 (20.7%), 44 (32.6%), and 6 (4.4%) were class I, II, III and IV respectively. Conclusion Log D6.0 showed better prediction capability than log P. Metoprolol as permeability internal standard was more conservative than labetalol. PMID:22615645

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

PubMed

Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

2014-03-18

To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Patient, hospital, and neighborhood factors associated with treatment of early-stage breast cancer among Asian American women in California

PubMed Central

Gomez, Scarlett Lin; Press, David J.; Lichtensztajn, Daphne; Keegan, Theresa H. M.; Shema, Sarah J.; Le, Gem M.; Kurian, Allison W.

2012-01-01

Background Clinical guidelines recommend breast conserving surgery (BCS) with radiation as a viable alternative to mastectomy for treatment of early-stage breast cancer. Yet, Asian Americans (AA) are more likely than other groups to have mastectomy or omit radiation after BCS. Methods We applied polytomous logistic regression and recursive partitioning (RP) to analyze factors associated with mastectomy, or BCS without radiation, among 20,987 California AAs diagnosed with stage 0–II breast cancer from 1990–2007. Results The percentage receiving mastectomy ranged from 40% among US-born Chinese to 58% among foreign-born Vietnamese. Factors associated with mastectomy included tumor characteristics such as larger tumor size, patient characteristics such as older age and foreign birthplace among some AA ethnicities, and additional factors including hospital (smaller hospital size, not NCI cancer center, low socioeconomic status (SES) patient composition, and high hospital AA patient composition) and neighborhood characteristics (ethnic enclaves of low SES). These hospital and neighborhood characteristics were also associated with BCS without radiation. Through RP, the highest mastectomy subgroups were defined by tumor characteristics such as size and anatomic location, in combination with diagnosis year and nativity. Conclusions Tumor characteristics and, secondarily, patient, hospital and neighborhood factors, are predictors of mastectomy and omission of radiation following BCS among AAs. Impact By focusing on interactions among patient, hospital, and neighborhood factors in the differential receipt of breast cancer treatment, our study identifies subgroups of interest for further study, and translation into public health and patient-focused initiatives to ensure that all women are fully informed about treatment options. PMID:22402290

Pediatric Biopharmaceutical Classification System: Using Age-Appropriate Initial Gastric Volume.

PubMed

Shawahna, Ramzi

2016-05-01

Development of optimized pediatric formulations for oral administration can be challenging, time consuming, and financially intensive process. Since its inception, the biopharmaceutical classification system (BCS) has facilitated the development of oral drug formulations destined for adults. At least theoretically, the BCS principles are applied also to pediatrics. A comprehensive age-appropriate BCS has not been fully developed. The objective of this work was to provisionally classify oral drugs listed on the latest World Health Organization's Essential Medicines List for Children into an age-appropriate BCS. A total of 38 orally administered drugs were included in this classification. Dose numbers were calculated using age-appropriate initial gastric volume for neonates, 6-month-old infants, and children aging 1 year through adulthood. Using age-appropriate initial gastric volume and British National Formulary age-specific dosing recommendations in the calculation of dose numbers, the solubility classes shifted from low to high in pediatric subpopulations of 12 years and older for amoxicillin, 5 years, 12 years and older for cephalexin, 9 years and older for chloramphenicol, 3-4 years, 9-11 and 15 years and older for diazepam, 18 years and older (adult) for doxycycline and erythromycin, 8 years and older for phenobarbital, 10 years and older for prednisolone, and 15 years and older for trimethoprim. Pediatric biopharmaceutics are not fully understood where several knowledge gaps have been recently emphasized. The current biowaiver criteria are not suitable for safe application in all pediatric populations.

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

PubMed

Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr

2018-02-01

The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

Supramolecular Cocrystals of Gliclazide: Synthesis, Characterization and Evaluation.

PubMed

Chadha, Renu; Rani, Dimpy; Goyal, Parnika

2017-03-01

To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties. Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters. The generation of new, single and pure crystal forms was characterized by DSC and PXRD. The crystal structure determination from PXRD revealed the existence of both cocrystals in triclinic (P-1) crystal system. The hydrogen bonded network, determined by material studio was well supported by shifts in FTIR and SSNMR. Both the new solid forms displayed improved solubility, IDR, antidiabetic activity and pharmacokinetic parameters as compared to GL. The improvement in these physicochemical and biopharmaceutical properties corroborated the fact that the supramolecular cocrystallization may be useful in the development of pharmaceutical crystalline materials with interesting network and properties.

Analysis of the cellulose synthase operon genes, bcsA, bcsB, and bcsC in Cronobacter species: Prevalence among species and their roles in biofilm formation and cell-cell aggregation.

PubMed

Hu, Lan; Grim, Christopher J; Franco, Augusto A; Jarvis, Karen G; Sathyamoorthy, Vengopal; Kothary, Mahendra H; McCardell, Barbara A; Tall, Ben D

2015-12-01

Cronobacter species are emerging food-borne pathogens that cause severe sepsis, meningitis, and necrotizing entercolitis in neonates and infants. Bacterial pathogens such as Escherichia coli and Salmonella species produce extracellular cellulose which has been shown to be involved in rugosity, biofilm formation, and host colonization. In this study the distribution and prevalence of cellulose synthase operon genes (bcsABZC) were determined by polymerase chain reaction (PCR) analysis in 231 Cronobacter strains isolated from clinical, food, environmental, and unknown sources. Furthermore, bcsA and bcsB isogenic mutants were constructed in Cronobacter sakazakii BAA894 to determine their roles. In calcofluor binding assays bcsA and bcsB mutants did not produce cellulose, and their colonial morphotypes were different to that of the parent strain. Biofilm formation and bacterial cell-cell aggregation were significantly reduced in bcsA and bcsB mutants compared to the parental strain. bcsA or bcsAB PCR-negative strains of C. sakazakii did not bind calcofluor, and produced less biofilm and cell-cell aggregation compared to strains possessing bcsAB genes. These data indicated that Cronobacter bcsABZC were present in all clinical isolates and most of food and environmental isolates. bcsA and bcsB genes of Cronobacter were necessary to produce cellulose, and were involved in biofilm formation and cell-cell aggregation. Published by Elsevier Ltd.

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets

PubMed Central

Anumolu, P. D.; Sunitha, G.; Bindu, S. Hima; Satheshbabu, P. R.; Subrahmanyam, C. V. S.

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias. PMID:26180277

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets.

PubMed

Anumolu, P D; Sunitha, G; Bindu, S Hima; Satheshbabu, P R; Subrahmanyam, C V S

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias.

BCS: the Scientific "Love of my Life"

NASA Astrophysics Data System (ADS)

Anderson, Philip W.

After short comments on my early addenda to BCS — gauge invariance and the Anderson-Higgs mechanism, the dirty superconductor "theorem," and the spinor representation — I focus on the interaction mechanisms which cause electron-electron pairing. These bifurcate into two almost non-overlapping classes. In order to cause electrons to pair in spite of the strong, repulsive, instantaneous Coulomb vertex, the electrons can evade each others' propinquity on the same site at the same time either dynamically, by retaining D° (s-wave) relative symmetry, but avoiding each other in time — called "dynamic screening" — or by assuming a non-symmetric relative wave function, avoiding each other in space. All simple metals and alloys, including all the (so far) technically useful superconductors, follow the former scheme. But starting with the first discovery of "heavy-electron" super-conductors in 1979, and continuing with the "organics" and the magnetic transition metal compounds such as the cuprates and the iron pnictides, it appears that the second class may turn out to be numerically superior and theoretically more fascinating. The basic interaction in many of these cases appears to be the "kinetic exchange" or superexchange characteristic of magnetic insulators.

An outcome survey of 43 patients with Budd-Chiari syndrome due to Behçet's syndrome followed up at a single, dedicated center.

PubMed

Seyahi, Emire; Caglar, Erkan; Ugurlu, Serdal; Kantarci, Fatih; Hamuryudan, Vedat; Sonsuz, Abdullah; Melikoglu, Melike; Yurdakul, Sebahattin; Yazici, Hasan

2015-04-01

Behçet's syndrome (BS) is a well-recognized cause of Budd-Chiari syndrome (BCS); however, information about its clinical characteristics and outcome is limited. We reviewed the records of about 9000 patients with BS registered at the multidisciplinary Behçet's syndrome outpatient clinic at Cerrahpasa Medical Faculty between July 1977 and October 2013. We identified 43 (40 M/3 F) patients who were diagnosed as having BCS. Their outcome was evaluated between September 2012 and October 2013. In total, 33 patients (77%) had presented with liver-related symptoms (Group I), while 10 (23%) were asymptomatic for liver disease (Group II). This latter group had presented with symptoms related to the presence of major vessel disease such as fever, leg swelling, or dyspnea. The site of venous obstruction determined in 41 patients was inferior vena cava (IVC) and hepatic veins combined in 25 (61%), IVC alone in 12 (29%), and only hepatic veins in 4 patients (10%). The number of patients with concurrent obstruction in the hepatic veins and the IVC was less in Group II than in Group I (3/10 vs 22/31, p = 0.06). A total of 20 (19 M/1 F) patients (47%) had died at a median of 10 months after diagnosis. Mortality was significantly lower in Group II (10%) than in Group I (58%), (p = 0.011). By the end of the survey, 23 patients were alive, of whom 21 could be re-evaluated at the clinic. BCS associated with BS is usually due to IVC thrombosis with or without hepatic vein thrombosis. Silent cases exist and have a better prognosis. The mortality rate among the patients symptomatic for liver disease remains high. Copyright © 2014 Elsevier Inc. All rights reserved.

Toward an In Vivo Dissolution Methodology: A Comparison of Phosphate and Bicarbonate Buffers

PubMed Central

Sheng, Jennifer J.; McNamara, Daniel P.; Amidon, Gordon L.

2011-01-01

Purpose To evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin, to illustrate the dependence of buffer differential on biopharmaceutical properties of BCS II weak acids, and to recommend phosphate buffers equivalent to bicarbonates. Methods The intrinsic dissolution rates of, ketoprofen and indomethacin, were experimentally measured using rotating disk method at 37°C in USP SIF/FaSSIF and various concentrations of bicarbonates. Theoretical models including an improved reaction plane model and a film model were applied to estimate the surrogate phosphate buffers equivalent to the bicarbonates. Results Experimental results show that the intrinsic dissolution rates of ketoprofen and indomethacin, in USP and FaSSIF phosphate buffers are 1.5–3.0 times of that in the 15 mM bicarbonates. Theoretical analysis demonstrates that the buffer differential is largely dependent on the drug pKa and secondly on solubility, and weakly dependent on the drug diffusivity. Further, in accordance with the drug pKa, solubility and diffusivity, simple phosphate surrogate was proposed to match an average bicarbonate value (15 mM) of the upper gastrointestinal region. Specifically, phosphate buffers of 13–15 mM and 3–4 mM were recommended for ketoprofen and indomethacin, respectively. For both ketoprofen and indomethacin, the intrinsic dissolution using the phosphate surrogate buffers closely approximated the 15 mM bicarbonate buffer. Conclusions This work demonstrates the substantial difference between pharmaceutical phosphates and physiological bicarbonates in determining the drug intrinsic dissolution rates of BCS II weak acids, such as ketoprofen and indomethacin. Surrogate phosphates were recommended in order to closely reflect the in vivo dissolution of ketoprofen and indomethacin in gastrointestinal bicarbonates, which has significant implications for defining buffer systems for BCS II weak acids in developing in vitro bioequivalence dissolution methodology. PMID:19183104

Improved perception of communication and compliance with a revised, intensive care unit-specific bedside communication sheet.

PubMed

Aponte-Patel, Linda; Sen, Anita

2015-01-01

Although many pediatric intensive care units (PICUs) use beside communication sheets (BCSs) to highlight daily goals, the optimal format is unknown. A site-specific BCS could improve both PICU communication and compliance completing the BCS. Via written survey, PICU staff at an academic children's hospital provided recommendations for improving and revising an existing BCS. Pre- and post-BCS revision, PICU staff were polled regarding PICU communication and BCS effectiveness, and daily compliance for completing the BCS was monitored. After implementation of the revised BCS, staff reporting "excellent" or "very good" day-to-day communication within the PICU increased from 57% to 77% (P = .02). Compliance for completing the BCS also increased significantly (75% vs 83%, P = .03). Introduction of a focused and concise BCS tailored to a specific PICU leads to improved perceptions of communication by PICU staff and increased compliance completing the daily BCS. © The Author(s) 2014.

Relationship between body condition score at calving and reproductive performance in young postpartum cows grazing native range.

PubMed

Mulliniks, J T; Cox, S H; Kemp, M E; Endecott, R L; Waterman, R C; Vanleeuwen, D M; Petersen, M K

2012-08-01

Body condition score is used as a management tool to predict competency of reproduction in beef cows. Therefore, a retrospective study was performed to evaluate association of BCS at calving with subsequent pregnancy rate, days to first postpartum ovulation, nutrient status (assessed by blood metabolites), and calf BW change in 2- and 3-yr-old cows (n = 351) managed and selected to fit their environment of grazing native range over 6 yr at the Corona Range and Livestock Research Center, Corona, NM. Cows were managed similarly before calving, without manipulation of management, to achieve predetermined BCS at parturition. Palpable BCS (scale of 1 to 9) were determined by 2 experienced technicians before calving. Cows were classified to 1 of 3 BCS groups prior calving: BCS 4 (mean BCS = 4.3 ± 0.02), 5 (mean BCS = 5.0 ± 0.03), or 6 (mean BCS = 5.8 ± 0.06). Cows were weighed weekly after calving and serum was collected once weekly (1 yr) or twice weekly (5 yr) for progesterone analysis to estimate first postpartum ovulation beginning 35 d postpartum. Year effects also were evaluated, with years identified as either above or below average precipitation. Days to first postpartum ovulation did not differ among calving BCS groups (P = 0.93). Pregnancy rates were not influenced by calving BCS (P = 0.83; 92%, 91%, 90% for BCS 4, 5, and 6, respectively). Days to BW nadir was not influenced by BCS at calving (P = 0.95). Cow BW was different at all measuring points (P < 0.01) with BCS 6 cows having the heaviest BW and cows with BCS 4 the lightest. Cows with calving BCS 4 and 5 lost more (P = 0.06) BW from the initiation of the study to the end of breeding than cows with BCS 6. However, cow BW change at all other measurement periods was not different (P ≥ 0.49) among calving BCS groups. Serum glucose and NEFA concentrations were not influenced by calving BCS (P ≥ 0.51). Calf BW at birth (P = 0.60), branding (55-d BW; P = 0.76), and weaning (205-d BW; P = 0.60) were not impacted by cow calving BCS. Body condition score did not influence overall pregnancy rates, indicating that young cows can have a reduced BCS and still be reproductively punctual. Therefore, these results indicate that reproductive performance of young cows with reduced BCS may not be affected when managed in extensive range conditions.

Low-dose natural prostaglandin F2α (dinoprost) at timed insemination improves conception rate in dairy cattle.

PubMed

Ambrose, Divakar J; Gobikrushanth, Mohanathas; Zuidhof, Sjoert; Kastelic, John P

2015-03-01

The primary objective was to determine if low doses of PGF2α (dinoprost) given intramuscularly (im) concurrent with timed artificial insemination (TAI) would improve conception rates in dairy cattle. A secondary objective was to determine if body condition score (BCS) and parity would influence conception rates, either independently or in interaction with PGF2α treatment. In experiment I, 307 lactating Holstein cows were randomly assigned to receive either 5-mg PGF2α im (PGF2α treated, n = 154) or 0-mg PGF2α (control, n = 153) at TAI (Day 0). Blood samples were obtained on Days -10, -3, 0, and 7 to determine plasma progesterone (P4) concentrations. Pregnancy was confirmed 30 to 32 days after insemination by transrectal ultrasonography. In experiment II, 451 cows were randomly assigned to receive either 10-mg PGF2α im (PGF2α treated, n = 226) or 0-mg PGF2α (control, n = 225) at TAI, and pregnancy was confirmed 45 to 50 days after TAI by palpation per rectum. Pregnancy data were analyzed by CATMOD (SAS). In experiment I, PGF2α treatment, BCS, and parity did not affect conception rate (35.7% vs. 37.0% for PGF2α treated vs. control; P > 0.05). However, in experiment II, conception rates were higher in cows given 10-mg PGF2α than those in control cows (45.8% vs. 36.0%; P < 0.05), in cows with high BCS than in cows with low BCS (52.1% vs. 30.4%; P < 0.01), and in primiparous than in multiparous cows (47.6% vs. 34.4%; P < 0.01), but their interaction with PGF2α treatment did not affect conception rates. In summary, 5 mg of PGF2α given im concurrent with TAI failed to enhance conception rate in lactating dairy cows, whereas 10 mg of PGF2α significantly increased conception rate. Copyright © 2015 Elsevier Inc. All rights reserved.

[Relationship between factor v Leiden mutation and Chinese Budd-Chiari syndrome and its clinical significance].

PubMed

Feng, B; Xu, K; Jiang, H

2000-05-01

To investigate the relationship between factor v Leiden (FvL) mutation and Chinese sporadic Budd-Chiari syndrome (BCS), familial BCS, and to explore the significance of FvL mutation in the etiology of BCS. Twenty-five patients with sporadic BCS, 6 patients with familial BCS (from A and B families), 39 both A and B family members, and 31 healthy persons were detected for FvL mutation with PCR. Meantime, two family members were explored for the related etiology of BCS. Factor V Leiden mutation was detected in 4 of 6 patients with familial BCS and in 2 family members. AIII(7,11,15) and BII(10), AII(2) and BIII(5) were found FvL mutation, and mutation was heterzygous. FvL mutation in the two degrees was compatible with Mendel hereditery law. The frequency of FvL mutation in 31 BCS and 31 healthy persons showed no statistical significance: but the frequency of FvL mutation between the familial BCS and healthy persons showed statistical significance. Ten persons in A family had varicose vein of the low extremeties, which was compatible with autosomal dominant inheritance. FvL mutation is related to Chinese familial BCS, but is not related to Chinese sporadic BCS. FvL mutation may be a underlying pathogenicity of familial BCS. Varicose vein of the low extremeties may be one of the pathogenicity of familial BCS.

Solar Energy Education. Reader, Part II. Sun story. [Includes glossary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1981-05-01

Magazine articles which focus on the subject of solar energy are presented. The booklet prepared is the second of a four part series of the Solar Energy Reader. Excerpts from the magazines include the history of solar energy, mythology and tales, and selected poetry on the sun. A glossary of energy related terms is included. (BCS)

Chemosensory brush cells of the trachea. A stable population in a dynamic epithelium.

PubMed

Saunders, Cecil J; Reynolds, Susan D; Finger, Thomas E

2013-08-01

Tracheal brush cells (BCs) are specialized epithelial chemosensors that use the canonical taste transduction cascade to detect irritants. To test whether BCs are replaced at the same rate as other cells in the surrounding epithelium of adult mice, we used 5-bromo-2'-deoxyuridine (BrdU) to label dividing cells. Although scattered BrdU-labeled epithelial cells are present 5-20 days after BrdU, no BCs are labeled. These data indicate that BCs comprise a relatively static population. To determine how BCs are generated during development, we injected 5-day-old mice with BrdU and found labeled BCs and non-BC epithelial cells 5 days after BrdU. During the next 60 days, the percentage of labeled BCs increased, whereas the percentage of other labeled cell types decreased. These data suggest that BCs are generated from non-BC progenitor cells during postnatal tracheal growth. To test whether the adult epithelium retains the capacity to generate BCs, tracheal epithelial cells were recovered from adult mice and grown in an air-liquid interface (ALI) culture. After transition to differentiation conditions, BCs are detected, and comprise 1% of the total cell population by Day 14. BrdU added to cultures before the differentiation of BCs was chased into BCs, indicating that the increase in BC density is attributable to the proliferation of a non-BC progenitor. We conclude that: (1) BCs are normally a static population in adult mice; (2) BC progenitors proliferate and differentiate during neonatal development; and (3) BCs can be regenerated from a proliferative population resident in adult epithelium.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edwards-Bennett, Sophia M., E-mail: edwards2@mskcc.org; Jacks, Lindsay M.; McCormick, Beryl

Purpose: Population-based studies have reported that as many of 35% of black women do not undergo radiotherapy (RT) after breast conservation surgery (BCS). The objective of the present study was to determine whether this trend persisted at a large multidisciplinary cancer center, and to identify the factors that predict for noncompliance with RT and determine the outcomes for this subset of patients. Methods and Materials: Between January 2002 and December 2007, 83 black women underwent BCS at Memorial Sloan-Kettering Cancer Center and were therefore eligible for the present study. Of the 83 women, 38 (46%) had Stage I, 38 (46%)more » Stage II, and 7 (8%) Stage III disease. Of the study cohort, 31 (37%) had triple hormone receptor-negative tumors. RT was recommended for 81 (98%) of the 83 patients (median dose, 60 Gy). Results: Of the 81 women, 12 (15%) did not receive the recommended adjuvant breast RT. Nonreceipt of chemotherapy (p = .003) and older age (p = .009) were associated with nonreceipt of RT. With a median follow-up of 70 months, the 3-year local control, locoregional control, recurrence-free survival, disease-free survival, and overall survival rate was 99% (actuarial 5-year rate, 97%), 96% (actuarial 5-year rate, 93%), 95% (actuarial 5-year rate, 92%), 92% (actuarial 5-year rate, 89%), and 95% (actuarial 5-year rate, 91%), respectively. Conclusion: We found a greater rate of utilization adjuvant breast RT (85%) among black women after BCS than has been reported in recent studies, indicating that excellent outcomes are attainable for black women after BCS when care is administered in a multidisciplinary cancer center.« less

Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast Conservation Surgery: A Comparative Study from a Developing Country.

PubMed

Agarwal, Gaurav; Sonthineni, Chaitra; Mayilvaganan, Sabaretnam; Mishra, Anjali; Lal, Punita; Agrawal, Vinita

2018-05-01

In India and other developing countries, breast conservation surgery (BCS) rates in breast cancer patients are low due to advanced disease at presentation and misconceptions about BCS outcomes. Many patients presenting with large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant chemotherapy (NACT) BCS, safety of which is not as well established as that of primary BCS. This retrospective study compared pathological and surgical outcome parameters in patients undergoing primary and post-NACT BCS. All non-metastatic breast cancer patients undergoing BCS during 2011-2015 with 1-year follow-up were included. Outcome parameters in form of margin infiltration, ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were compared between primary and post-NACT BCS patients groups. One hundred and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT BCS. Patients in both groups underwent similar multimodality treatment as per institutional protocols. Post-NACT patients more frequently required oncoplastic volume displacement or replacement surgery (p = 0.002). Re-excision of infiltrated margins was needed more frequently in primary BCS compared with post-NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR-free survival did not differ significantly between the groups in stage-wise comparison. Post-NACT BCS is safe even in large tumors and LABC, though many require oncoplastic procedures for satisfactory cosmesis. In a developing country where many patients present with large breast cancers or LABC, the benefits of BCS can be offered to a majority with the help of NACT, without compromising the chances of cure.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics.

PubMed

Locher, Kathrin; Borghardt, Jens M; Frank, Kerstin J; Kloft, Charlotte; Wagner, Karl G

2016-08-01

Biphasic dissolution models are proposed to have good predictive power for the in vivo absorption. The aim of this study was to improve our previously introduced mini-scale dissolution model to mimic in vivo situations more realistically and to increase the robustness of the experimental model. Six dissolved APIs (BCS II) were tested applying the improved mini-scale biphasic dissolution model (miBIdi-pH-II). The influence of experimental model parameters including various excipients, API concentrations, dual paddle and its rotation speed was investigated. The kinetics in the biphasic model was described applying a one- and four-compartment pharmacokinetic (PK) model. The improved biphasic dissolution model was robust related to differing APIs and excipient concentrations. The dual paddle guaranteed homogenous mixing in both phases; the optimal rotation speed was 25 and 75rpm for the aqueous and the octanol phase, respectively. A one-compartment PK model adequately characterised the data of fully dissolved APIs. A four-compartment PK model best quantified dissolution, precipitation, and partitioning also of undissolved amounts due to realistic pH profiles. The improved dissolution model is a powerful tool for investigating the interplay between dissolution, precipitation and partitioning of various poorly soluble APIs (BCS II). In vivo-relevant PK parameters could be estimated applying respective PK models. Copyright © 2016 Elsevier B.V. All rights reserved.

Behcet's disease in Budd-Chiari syndrome.

PubMed

Desbois, Anne Claire; Rautou, Pierre Emmanuel; Biard, Lucie; Belmatoug, Nadia; Wechsler, Bertrand; Resche-Rigon, Mathieu; Zarrouk, Virginie; Fantin, Bruno; de Chambrun, M Pineton; Cacoub, Patrice; Valla, Dominique; Saadoun, David; Plessier, Aurélie

2014-01-01

Behcet's disease (BD) is a well-known cause of Budd-Chiari syndrome (BCS). Data are lacking on the presentation and outcome of BCS related to BD. We investigated the relationship between BD and BCS in 14 patients with both diseases and compared the results to 92 BCS patients without BD. Male gender (p = 0.003), North African origin (P = 0.007) and inferior vena cava obstruction (P < 0.0001) were more frequent in patients with BD and BCS than in those with BCS alone and the plasma C-reactive protein level was higher (p = 0.003). Two of the patients with the combined diseases underwent recanalization of the vena cava and the hepatic veins, none received transjugular intrahepatic portosystemic shunts (TIPS), one received a surgical shunt and one underwent liver transplantation. TIPS were less frequent in patients with BD and BCS than in those with BCS alone (P = 0.019). Eighty six per cent of patients with BCS and BD received corticosteroids and immunosuppressive therapy. The 5-year transplantation-free survival rate was 63% in patients with BCS alone and 91% in those without BD (P = 0.11). In our series and in the literature, a high number of patients [12 (61.5%) and 11 (64.7%) respectively] treated with anticoagulation and corticosteroids and/or immunosuppressants did not require invasive treatment. This study shows a higher frequency of IVC obstruction in patients with BCS and BD. Medical treatment with anticoagulation and immunosuppressive agents may improve the symptoms of BCS. Therefore early management with immunosuppressive and anticoagulation therapy appears to be the treatment of choice in patients with BCS and BD.

Isotope and multiband effects in layered superconductors.

PubMed

Bussmann-Holder, Annette; Keller, Hugo

2012-06-13

In this review we consider three classes of superconductors, namely cuprate superconductors, MgB(2) and the new Fe based superconductors. All of these three systems are layered materials and multiband compounds. Their pairing mechanisms are under discussion with the exception of MgB(2), which is widely accepted to be a 'conventional' electron-phonon interaction mediated superconductor, but extending the Bardeen-Cooper-Schrieffer (BCS) theory to account for multiband effects. Cuprates and Fe based superconductors have higher superconducting transition temperatures and more complex structures. Superconductivity is doping dependent in these material classes unlike in MgB(2) which, as a pure compound, has the highest values of T(c) and a rapid suppression of superconductivity with doping takes place. In all three material classes isotope effects have been observed, including exotic ones in the cuprates, and controversial ones in the Fe based materials. Before the area of high-temperature superconductivity, isotope effects on T(c) were the signature for phonon mediated superconductivity-even when deviations from the BCS value to smaller values were observed. Since the discovery of high T(c) materials this is no longer evident since competing mechanisms might exist and other mediating pairing interactions are discussed which are of purely electronic origin. In this work we will compare the three different material classes and especially discuss the experimentally observed isotope effects of all three systems and present a rather general analysis of them. Furthermore, we will concentrate on multiband signatures which are not generally accepted in cuprates even though they are manifest in various experiments, the evidence for those in MgB(2), and indications for them in the Fe based compounds. Mostly we will consider experimental data, but when possible also discuss theoretical models which are suited to explain the data.

Evaluation of body condition score measured throughout lactation as an indicator of fertility in dairy cattle.

PubMed

Banos, G; Brotherstone, S; Coffey, M P

2004-08-01

Body condition score (BCS) records of primiparous Holstein cows were analyzed both as a single measure per animal and as repeated measures per sire of cow. The former resulted in a single, average, genetic evaluation for each sire, and the latter resulted in separate genetic evaluations per day of lactation. Repeated measure analysis yielded genetic correlations of less than unity between days of lactation, suggesting that BCS may not be the same trait across lactation. Differences between daily genetic evaluations on d 10 or 30 and subsequent daily evaluations were used to assess BCS change at different stages of lactation. Genetic evaluations for BCS level or change were used to estimate genetic correlations between BCS measures and fertility traits in order to assess the capacity of BCS to predict fertility. Genetic correlation estimates with calving interval and non-return rate were consistently higher for daily BCS than single measure BCS evaluations, but results were not always statistically different. Genetic correlations between BCS change and fertility traits were not significantly different from zero. The product of the accuracy of BCS evaluations with their genetic correlation with the UK fertility index, comprising calving interval and non-return rate, was consistently higher for daily than for single BCS evaluations, by 28 to 53%. This product is associated with the conceptual correlated response in fertility from BCS selection and was highest for early (d 10 to 75) evaluations.

Effect of black cumin seeds on growth performance, nutrient utilization, immunity, gut health and nitrogen excretion in broiler chickens.

PubMed

Kumar, Pawan; Patra, Amlan Kumar; Mandal, Guru Prasad; Samanta, Indranil; Pradhan, Saktipada

2017-08-01

Use of antibiotic growth promoters (AB) as feed additives in broiler chickens poses risks due to cross-resistance amongst pathogens and residues in tissues. The aim of this study was to evaluate the effect of dietary supplementation of black cumin seeds (BCS) as a natural growth promoter in chickens on nutrient utilization, intestinal microbiota and morphology, immunity, antioxidant status, protein deposition in muscles and nitrogen excretion. Broiler chickens were fed BCS at 0, 5, 10 and 20 g kg -1 diet. Body weight gain tended to increase (P = 0.10) and daily feed intake increased quadratically with increasing concentrations of BCS in the diets. Supplementation of BCS resulted in a tendency to decrease feed conversion efficiency on days 28-42. Metabolizability of nutrients increased linearly with increasing doses of BCS. Protein deposition in thigh and breast muscles was increased and nitrogen excretion was reduced by BCS and AB compared with the control (CON). Intestinal morphology in the duodenum, jejunum and ileum was not generally affected by BCS. Counts of total bacteria, Escherichia coli, Lactobacillus spp. and Clostridium spp. were not affected by BCS and AB compared with CON, but Salmonella spp. decreased linearly (P = 0.05) with increasing doses of BCS. Antibody titers against Newcastle disease virus on day 35 increased quadratically (P < 0.001) with increasing doses of BCS. Concentrations of glucose and triglyceride in blood were not affected by BCS. Concentrations of cholesterol decreased linearly while the concentration of total protein increased linearly with increasing doses of BCS. The use of dietary BCS may improve growth performance, immunity and nutrient utilization in broiler chickens. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Scientific publications on portal vein thrombosis and Budd-Chiari syndrome: a global survey of the literature.

PubMed

Qi, Xingshun; Jia, Jia; Ren, Weirong; Yang, Man; De Stefano, Valerio; Wang, Juan; Fan, Daiming

2014-03-01

Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) are two rare vascular disorders of the liver that can lead to life-threatening complications. We conducted a global survey to systematically analyze the scientific publications in the fields of PVT and BCS. All papers regarding PVT and BCS were identified via the PubMed, EMBASE, and Cochrane library databases. The publication year, country, type of paper, study design, and number of citations were summarized. Good quality papers were defined as those in which a high proportion of homogeneous patients with BCS and/or PVT was observed. We identified 6691 and 4325 papers regarding PVT and BCS, respectively. The number of papers gradually increased over time. Researchers from the USA published the greatest number of papers (PVT: n=1418; BCS: n=888). Clinical studies were the most common type of paper (PVT: n=5395; BCS n=3171), but fewer than half of these observed more than 10 patients (PVT: n=2667/5395; BCS: n=1092/3171). Furthermore, fewer than half of the clinical studies with more than 10 patients were of good quality (PVT: 976/2667; BCS: 466/1092). According to the study design, the good quality papers were classified as cohort studies (PVT: n=865; BCS: n=421), case-control studies (PVT: n=98; BCS: n=45), and randomized controlled trials (PVT: n=13; BCS: n=0). The 5 most frequently cited original articles and guidelines/consensuses were also listed. Despite an increase in the number of papers regarding PVT and BCS over time, most of the papers had a small sample size, suggesting the necessity of large cohort studies or randomized controlled trials.

Influence of body condition score on carcass characteristics and subprimal yield from cull beef cows.

PubMed

Apple, J K; Davis, J C; Stephenson, J; Hankins, J E; Davis, J R; Beaty, S L

1999-10-01

Mature beef cows (n = 83) were slaughtered to measure the influence of body condition score (BCS) on carcass characteristics and subprimal yields. All cows were weighed and assigned BCS, based on a 9-point scale, 24 h before slaughter. Cows were slaughtered, and, after a 48-h chilling period, quality and yield grade data were collected on the left side of each carcass. The right side was quartered, fabricated into primal cuts, and weighed. Each primal cut was further processed into boneless subprimal cuts, minor cuts, lean trim, fat, and bone. Cuts were progressively trimmed to 6.4 and 0 mm of external and visible seam fat. Weights were recorded at all stages of fabrication, and subprimal yields were calculated as a percentage of the chilled carcass weight. Live weight, carcass weight, dressing percentage, fat thickness, longissimus muscle area, muscle:bone ratio, and numerical yield grade increased linearly (P = .0001) and predicted cutability and actual muscle-to-fat ratio decreased linearly (P = .0001) as BCS increased from 2 to 8. Carcasses from BCS-8 cows had the most (P<.05) marbling. The percentage of carcasses grading U.S. Utility, or higher, was 16.7, 20.0, 63.6, 43.3, 73.3, 100.0, and 100.0% for cows assigned a BCS of 2, 3, 4, 5, 6, 7, and 8, respectively. At 6.4 mm of fat trim, carcasses from BCS-5 cows had higher (P<.05) shoulder clod yields than carcasses from cows having a BCS of 6, 7, and 8. Carcasses of BCS-2 cows had lower (P<.05) strip loin yields than carcasses from BCS-3, 4, 5, 6, and 7 cows. Top sirloin butt yields were higher (P<.05) for carcasses of BCS-2, 3, 4, and 5 cows than those of BCS-6, 7, or 8 cows. Carcasses from BCS-7 and 8 cows had lower (P<.05) tenderloin and inside round yields than carcasses of BCS-5, or less, cows. At both fat-trim levels, carcasses from BCS-5 cows had higher (P<.05) eye of round yields than cows assigned BCS of 2, 7, or 8. When subprimal cuts were trimmed to 6.4 mm of visible fat, carcasses from BCS-5 cows had higher (P<.05) total lean product yields than cows assigned a BCS of 2, 4, 7, and 8. Regardless of fat trim, total fat yields increased (P = .0001) and total bone yields decreased (P = .0001) linearly as BCS increased from 2 to 8. Although carcasses from BCS-5 and 6 cows had the highest yields of lean product, cattle producers and packers may benefit most by marketing and(or) purchasing BCS-6 cows because a higher percentage of their carcasses had quality characteristics deemed desirable for fabrication into boneless subprimal cuts.

Body condition score prior to parturition is associated with plasma and adipose tissue biomarkers of lipid metabolism and inflammation in Holstein cows.

PubMed

Alharthi, Abdulrahman; Zhou, Zheng; Lopreiato, Vincenzo; Trevisi, Erminio; Loor, Juan J

2018-01-01

Previous research has revealed a strong inflammatory response within adipose (AT) tissue during the transition into lactation. Whether this effect is a result of oxidative stress induced by lipolysis and fatty acid oxidation associated with differences in prepartum body condition score remains to be determined. The objectives of this study were to investigate systemic biomarkers of energy balance and inflammation and the expression of lipid metabolism- and inflammation-related genes in AT during the transition period in dairy cows. Twenty multiparous Holstein cows were retrospectively divided by body condition score (BCS) prior to parturition into two groups (10 cows/group): BCS ≤ 3.25 (LoBCS) and BCS ≥ 3.75 (HiBCS). Subcutaneous adipose tissue was biopsied from the tail-head region at d - 10, 7 and 20 relative to parturition. Plasma was used to evaluate biomarkers of energy balance (EBAL) [free fatty acids (NEFA), glycerol, insulin] and inflammation [IL-1β, haptoglobin, myeloperoxidase, and reactive oxygen metabolites (ROM)]. Although insulin concentration was not affected by BCS, NEFA was overall greater and glycerol lower in HiBCS cows. Greater activity of myeloperoxidase in plasma coincided with increased haptoglobin and IL-1β postpartum in LoBCS cows. Among genes related with oxidative stress, the expression of the cytosolic antioxidant enzyme SOD1 was greater in LoBCS compared to HiBCS. Cows in LoBCS compared with HiBCS had greater overall expression of ABDH5 and ATGL along with ADIPOQ , indicating enhanced basal lipolysis and secretion of adiponectin. Expression of CPT1A , ACADVL , and ACOX1 was greater overall in HiBCS than LoBCS indicating enhanced NEFA oxidation. Although the temporal increase in plasma NEFA regardless of BCS coincided with the profile of CPT1A , the gradual decrease in genes related with re-esterification of NEFA ( PCK1 ) and glycerol efflux ( AQP7 ) coupled with an increase in glycerol kinase ( GK ) suggested some stimulation of NEFA utilization within adipose tissue. This idea is supported in part by the gradual decrease in insulin regardless of BCS. Although expression of the inflammation-related gene toll-like receptor 4 ( TLR4 ) was greater in HiBCS versus LoBCS cows at -10 d, expression of TLR9 was greater in HiBCS versus LoBCS at 20 d. These profiles did not seem to be associated with concentrations of pro-inflammatory biomarkers or ROM. Overall, data indicated that cows with BCS 3.25 or lower before calving experienced greater alterations in systemic inflammation and basal lipolysis without excessive increases in NEFA plasma concentrations. Despite the greater plasma NEFA around parturition, cows with BCS 3.75 or higher seemed to have a more active system for catabolism of NEFA and utilization of glycerol within adipose tissue. A linkage between those pathways and risk of disorders postpartum remains to be determined.

Bacterial cellulose biosynthesis: diversity of operons, subunits, products, and functions.

PubMed

Römling, Ute; Galperin, Michael Y

2015-09-01

Recent studies of bacterial cellulose biosynthesis, including structural characterization of a functional cellulose synthase complex, provided the first mechanistic insight into this fascinating process. In most studied bacteria, just two subunits, BcsA and BcsB, are necessary and sufficient for the formation of the polysaccharide chain in vitro. Other subunits - which differ among various taxa - affect the enzymatic activity and product yield in vivo by modulating (i) the expression of the biosynthesis apparatus, (ii) the export of the nascent β-D-glucan polymer to the cell surface, and (iii) the organization of cellulose fibers into a higher-order structure. These auxiliary subunits play key roles in determining the quantity and structure of resulting biofilms, which is particularly important for the interactions of bacteria with higher organisms - leading to rhizosphere colonization and modulating the virulence of cellulose-producing bacterial pathogens inside and outside of host cells. We review the organization of four principal types of cellulose synthase operon found in various bacterial genomes, identify additional bcs genes that encode components of the cellulose biosynthesis and secretion machinery, and propose a unified nomenclature for these genes and subunits. We also discuss the role of cellulose as a key component of biofilms and in the choice between acute infection and persistence in the host. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quality defects in market beef and dairy cows and bulls sold through livestock auction markets in the Western United States: II. Relative effects on selling price.

PubMed

Ahola, J K; Foster, H A; Vanoverbeke, D L; Jensen, K S; Wilson, R L; Glaze, J B; Fife, T E; Gray, C W; Nash, S A; Panting, R R; Rimbey, N R

2011-05-01

Relative effects of Beef Quality Assurance (BQA)-related defects in market beef and dairy cows and bulls on selling price at auction was evaluated during 2008. The presence and severity of 23 BQA-related traits were determined during sales in Idaho, California, and Utah. Overall, 18,949 unique lots consisting of 23,479 animals were assessed during 125 dairy sales and 79 beef sales. Mean sale price ± SD (per 45.5 kg) for market beef cows, beef bulls, dairy cows, and dairy bulls was $45.15 ± 9.42, $56.30 ± 9.21, $42.23 ± 12.26, and $55.10 ± 9.07, respectively. When combined, all recorded traits explained 36% of the variation in selling price in beef cows, 35% in beef bulls, 61% in dairy cows, and 56% in dairy bulls. Premiums and discounts were determined in comparison with a "par" or "base" animal. Compared with a base BCS 5 beef cow (on a 9-point beef scale), BCS 1 to 4 cows were discounted (P < 0.0001), whereas premiums (P < 0.05) were estimated for BCS 6 to 8. Compared with a base BCS 3.0 dairy cow (on a 5-point dairy scale), more body condition resulted in a premium (P ≤ 0.001), whereas a less-than-desirable BCS of 2.0 or 2.5 was discounted (P < 0.0001). Emaciated or near-emaciated cows (beef BCS 1 or 2; dairy BCS 1.0 or 1.5) were discounted (P < 0.0001). Compared with base cows weighing 545 to 635 kg, lighter BW beef cows were discounted (P < 0.0001), whereas heavier beef cows received (P < 0.05) a premium. Compared with a base dairy cow weighing 636 to 727 kg, lighter BW cows were discounted (P < 0.0001), whereas heavier cows (727 to 909 kg) received a premium (P < 0.01). Beef and dairy cows with any evidence of lameness were discounted (P < 0.0001). Presence of ocular neoplasia in the precancerous stage discounted (P = 0.05) beef cows and discounted (P < 0.01) dairy cows, whereas at the cancerous stage, it discounted (P < 0.0001) all cows. Hide color influenced (P < 0.0001) selling price in beef cattle but had no effect (P = 0.17) in dairy cows. Animals that were visibly sick were discounted (P < 0.0001). Results suggest that improving BCS and BW, which producers can do at the farm or ranch level, positively affects sale price. Furthermore, animals that are visibly sick or have a defect associated with a possible antibiotic risk will be discounted. Ultimately, animals with minor quality defects should be sold in a timely manner before the defect advances and the discount increases.

Body condition score at parturition and postpartum supplemental fat effects on cow and calf performance.

PubMed

Lake, S L; Scholljegerdes, E J; Atkinson, R L; Nayigihugu, V; Paisley, S I; Rule, D C; Moss, G E; Robinson, T J; Hess, B W

2005-12-01

Three-year-old Angus x Gelbvieh beef cows nutritionally managed to achieve a BCS of 4 +/- 0.07 (479.3 +/- 36.3 kg of BW) or 6 +/- 0.07 (579.6 +/- 53.1 kg of BW) at parturition were used in a 2-yr experiment (n = 36/yr) to determine the effects of prepartum energy balance and postpartum lipid supplementation on cow and calf performance. Beginning 3 d postpartum, cows within each BCS were assigned randomly to be fed hay and a low-fat control supplement or supplements with either high-linoleate cracked safflower seeds or high-oleate cracked safflower seeds until d 60 of lactation. Diets were formulated to be isonitrogenous and isocaloric, and safflower seed supplements were provided to achieve 5% of DMI as fat. Ultrasonic 12th rib fat and LM area were lower (P < 0.001) for cows in BCS 4 compared with BCS 6 cows throughout the study. Cows in BCS 4 at parturition maintained (P = 0.02) condition over the course of the study, whereas cows in BCS 6 lost condition. No differences (P = 0.44 to 0.71) were detected for milk yield, milk energy, milk fat percentage, or milk lactose percentage because of BCS; however, milk protein percentage was less (P = 0.03) for BCS 4 cows. First-service conception rates did not differ (P = 0.22) because of BCS at parturition, but overall pregnancy rate was greater (P = 0.02) in BCS 6 cows. No differences (P = 0.48 to 0.83) were detected in calf birth weight or ADG because of BCS at parturition. Dietary lipid supplementation did not influence (P = 0.23 to 0.96) cow BW change, BCS change, 12th rib fat, LM area, milk yield, milk energy, milk fat percentage, milk lactose percentage, first service conception, overall pregnancy rates, or calf performance. Although cows in BCS of 4 at parturition seemed capable of maintaining BCS during lactation, the overall decrease in pregnancy rate indicates cows should be managed to achieve a BCS >4 before parturition to improve reproductive success.

Comparison of a classical with a highly formularized body condition scoring system for dairy cattle.

PubMed

Isensee, A; Leiber, F; Bieber, A; Spengler, A; Ivemeyer, S; Maurer, V; Klocke, P

2014-12-01

Body condition scoring is a common tool to assess the subcutaneous fat reserves of dairy cows. Because of its subjectivity, which causes limits in repeatability, it is often discussed controversially. Aim of the current study was to evaluate the impact of considering the cows overall appearance on the scoring process and on the validity of the results. Therefore, two different methods to reveal body condition scores (BCS), 'independent BCS' (iBCS) and 'dependent BCS' (dBCS), were used to assess 1111 Swiss Brown Cattle. The iBCS and the dBCS systems were both working with the same flowchart with a decision tree structure for visual and palpatory assessment using a scale from 2 to 5 with increment units of 0.25. The iBCS was created strictly complying with the defined frames of the decision tree structure. The system was chosen due to its formularized approach to reduce the influence of subjective impressions. By contrast, the dBCS system, which was in line with common practice, had a more open approach, where - besides the decision tree - the overall impression of the cow's physical appearance was taken into account for generating the final score. Ultrasound measurement of the back fat thickness (BFT) was applied as a validation method. The dBCS turned out to be the better predictor of BFT, explaining 67.3% of the variance. The iBCS was only able to explain 47.3% of the BFT variance. Within the whole data set, only 31.3% of the animals received identical dBCS and iBCS. The pin bone region caused the most deviations between dBCS and iBCS, but also assessing the pelvis line, the hook bones and the ligaments led to divergences in around 20% of the scored animals. The study showed that during the assessment of body condition a strict adherence to a decision tree is a possible source of inexact classifications. Some body regions, especially the pin bones, proved to be particularly challenging for scoring due to difficulties in assessing them. All the more, the inclusion of the overall appearance of the cow into the assessment process counteracted these errors and led to a fair predictability of BFT with the flowchart-based BCS. This might be particularly important, if different cattle types and breeds are assessed.

Elaboration of the α-model derived from the BCS theory of superconductivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, David C.

2013-10-14

The single-band α-model of superconductivity (Padamsee et al 1973 J. Low Temp. Phys. 12 387) is a popular model that was adapted from the single-band Bardeen–Cooper–Schrieffer (BCS) theory of superconductivity mainly to allow fits to electronic heat capacity versus temperature T data that deviate from the BCS prediction. The model assumes that the normalized superconducting order parameter Δ(T)/Δ(0) and therefore the normalized London penetration depth λL(T)/λL(0) are the same as in BCS theory, calculated using the BCS value αBCS ≈ 1.764 of α ≡ Δ(0)/kBTc, where kB is The single-band α-model of superconductivity (Padamsee et al 1973 J. Low Temp.more » Phys. 12 387) is a popular model that was adapted from the single-band Bardeen–Cooper–Schrieffer (BCS) theory of superconductivity mainly to allow fits to electronic heat capacity versus temperature T data that deviate from the BCS prediction. The model assumes that the normalized superconducting order parameter Δ(T)/Δ(0) and therefore the normalized London penetration depth λL(T)/λL(0) are the same as in BCS theory, calculated using the BCS value αBCS ≈ 1.764 of α ≡ Δ(0)/kBTc, where kB is Boltzmann's constant and Tc is the superconducting transition temperature. On the other hand, to calculate the electronic free energy, entropy, heat capacity and thermodynamic critical field versus T, the α-model takes α to be an adjustable parameter. Here we write the BCS equations and limiting behaviors for the superconducting state thermodynamic properties explicitly in terms of α, as needed for calculations within the α-model, and present plots of the results versus T and α that are compared with the respective BCS predictions. Mechanisms such as gap anisotropy and strong coupling that can cause deviations of the thermodynamics from the BCS predictions, especially the heat capacity jump at Tc, are considered. Extensions of the α-model that have appeared in the literature, such as the two-band model, are also discussed. Tables of values of Δ(T)/Δ(0), the normalized London parameter Λ(T)/Λ(0) and λL(T)/λL(0) calculated from the BCS theory using α = αBCS are provided, which are the same in the α-model by assumption. Tables of values of the entropy, heat capacity and thermodynamic critical field versus T for seven values of α, including αBCS, are also presented.« less

Assessing and managing body condition score for the prevention of metabolic disease in dairy cows.

PubMed

Roche, John R; Kay, Jane K; Friggens, Nic C; Loor, Juan J; Berry, Donagh P

2013-07-01

Body condition score (BCS) is an assessment of a cow's body fat (and muscle) reserves, with low values reflecting emaciation and high values equating to obesity. The intercalving profile of BCS is a mirror image of the milk lactation profile. The BCS at which a cow calves, her nadir BCS, and the amount of BCS lost after calving are associated with milk production, reproduction, and health. Genetics, peripartum nutrition, and management are factors that likely interact with BCS to determine the risk of health disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Influence of body condition score on live and carcass value of cull beef cows.

PubMed

Apple, J K

1999-10-01

Mature beef cows (n = 88) were slaughtered to determine the influence of body condition score (BCS) on carcass and live animal value. Cows were weighed and assigned a BCS (9-point scale), 24 h before slaughter. Hide and by-products weights were recorded during harvest. After a 48-h chill period, the right side of each carcass was fabricated into boneless subprimal cuts, minor cuts, lean trim, fat, and bone. Weights were recorded at all stages of fabrication. Carcass values (U.S.$/100 kg of hot carcass weight) were calculated for U.S. Utility and U.S. Cutter grades, as well as for the Utility/Cutter mix for each BCS. Gross value included the carcass value and the value of the hide and byproducts, whereas net value was calculated after harvest and fabrication costs and by-product value were considered. Live value (U.S.$/100 kg of live weight) was computed by dividing the net value by the animal's live weight 24 h before harvest. The value of the hide and by-products for BCS-2 cows was greater (P<.05) than for cows assigned a BCS of 3 through 8. Even though U.S. Utility carcasses from BCS-8 cows produced the least (P<.05) valuable subprimal cuts from the chuck, loin, and round, the gross and net values of BCS-8 cows were greater (P<.05) than those of BCS-3, 4, 5, and 6. Within the grade of U.S. Cutter, carcasses from BCS-6 cows had the highest (P<.05), and BCS-2 cows had the lowest (P<.05), gross and net values. Across the U.S. Utility/Cutter mix, cows designated with a BCS of 7 and 8 had greater (P<.05) gross and net values than cows assigned a BCS of 6, or lower. Live value increased linearly (P = .0002) from a low of $76.10/100 kg for BCS-2 cows to a high of $90.84/100 kg for BCS-7 cows. Carcasses from BCS-6 cows were relatively lean (8.4 mm of fat opposite of the longissimus muscle), and approximately 73% of the carcasses achieved a quality grade of U.S. Utility. Moreover, carcasses from BCS-6 cows had the highest total carcass values and live values comparable (P>.05) to BCS-7 cows. Information from this study can be used by the non-fed beef industry to establish a value-based marketing system. Data from this study would indicate that marketing cull beef cows at a BCS of 6 could optimize economic returns to both cow-calf producers and non-fed beef packers.

Role of superconducting energy gap in extended BCS-Bose crossover theory

NASA Astrophysics Data System (ADS)

Chávez, I.; García, L. A.; de Llano, M.; Grether, M.

2017-10-01

The generalized Bose-Einstein condensation (GBEC) theory of superconductivity (SC) is briefly surveyed. It hinges on three distinct new ingredients: (i) Treatment of Cooper pairs (CPs) as actual bosons since they obey Bose statistics, in contrast to BCS pairs which do not obey Bose commutation relations; (ii) inclusion of two-hole Cooper pairs (2hCPs) on an equal footing with two-electron Cooper pairs (2eCPs), thus making this a complete boson-fermion (BF) model; and (iii) inclusion in the resulting ternary ideal BF gas with particular BF vertex interactions that drive boson formation/disintegration processes. GBEC subsumes as special cases both BCS (having its 50-50 symmetry of both kinds of CPs) and ordinary BEC theories (having no 2hCPs), as well as the now familiar BCS-Bose crossover theory. We extended the crossover theory with the explicit inclusion of 2hCPs and construct a phase diagram of Tc/TF versus n/nf, where Tc and TF are the critical and Fermi temperatures, n is the total number density and nf that of unbound electrons at T = 0. Also, with this extended crossover one can construct the energy gap Δ(T)/Δ(0) versus T/Tc for some elemental SCs by solving at least two equations numerically: a gap-like and a number equation. In 50-50 symmetry, the energy gap curve agrees quite well with experimental data. But ignoring 2hCPs altogether leads to the gap curve falling substantially below that with 50-50 symmetry which already fits the data quite well, showing that 2hCPs are indispensable to describe SCs.

The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

PubMed Central

McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

2016-01-01

Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

Role of body condition score and body weight in the control of seasonal reproduction in Blanca Andaluza goats.

PubMed

Gallego-Calvo, L; Gatica, M C; Guzmán, J L; Zarazaga, L A

2014-12-30

The reproductive activity of 84 female Blanca Andaluza goats was monitored over 17 months to determine the role of body condition score (BCS) and body weight (BW) in its control. Following a 3×2 factorial experimental design, the animals were allocated to three groups: low BCS (≤2.50, n=24), medium BCS (BCS=2.75-3.00, n=31) and high BCS (≥3.25, n=29). The same animals, irrespective of the BCS group categorization, were also divided into two groups depending on BW: low BW (≤40kg, n=44) and high BW (>40kg, n=40). Oestrus was evaluated daily using vasectomised males. The ovulation rate was assessed by trans-rectal ultrasonography after the identification of oestrus. Ovulations were determined by monitoring the plasma progesterone concentration weekly. The BCS and BW were recorded once a week and nutritional status adjusted to maintain the initial differences in BW and BCS between the groups. Both BCS and BW had a significant (at least P<0.05) influence on the onset, the end, and the duration of the breeding season, with longer periods of reproductive activity recorded in does with a BCS of ≥2.75 and BW of >40kg. No significant interaction between these variables was observed. Some (11.7%) of the does in the groups with animals of BCS≥2.75 had ovulations during seasonal anoestrus. None of the does with a BCS of ≤2.5 had ovulations during seasonal anoestrus. The ovulation rate of the first and last oestrus was influenced by BW (P<0.01). These results demonstrate that Blanca Andaluza goats show marked reproductive seasonality that is clearly and independently modulated by BCS and BW. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of canine overweight and obesity on health-related quality of life.

PubMed

Yam, P S; Butowski, C F; Chitty, J L; Naughton, G; Wiseman-Orr, M L; Parkin, T; Reid, J

2016-05-01

Canine obesity is increasing in prevalence in the UK and raises concerns about dog welfare. This study compares the health-related quality of life (HRQL) of dogs of varying body condition: overweight and obese (BCS 4 and 5) versus non-overweight dogs (BCS 2 and 3), obese (BCS 5) versus non-overweight (BCS 2 and 3) and an overall comparison between all four BCS (BCS 2, 3, 4 and 5) using a novel, validated HRQL instrument which is both web and mobile tablet/phone app based. Of 271 dog owners who were approached, 174 completed a web-based instrument (2013) or a mobile tablet app instrument (2014) during the summers of 2013 and 2014. Automatically generated scores in four domains of HRQL (energetic/enthusiastic, happy/content, active/comfortable, calm/relaxed) were compared for dogs with each of the body condition scores (BCS 2-5). For all body condition scores a statistically significant difference was found between the HRQL scores in two of the domains: energetic/enthusiastic (p=0.02) and active comfortable (p=0.004). When BCS 2 and 3 were compared to BCS 4 and 5, statistical significance was found in the same two domains - energetic/enthusiastic (p=0.01) and active comfortable (p=0.001) - as it was in comparison of non-overweight (BCS 2 and 3) compared to obese dogs (BCS 5): energetic/enthusiastic (p=0.012) and active comfortable (p=0.004). These results suggest that overweight and obese dogs have a reduced HRQL in two of the domains compared to non-overweight dogs, and that differences in HRQL are detectable between BCS scores 2, 3, 4 and 5. Copyright © 2016 Elsevier B.V. All rights reserved.

BcsZ inhibits biofilm phenotypes and promotes virulence by blocking cellulose production in Salmonella enterica serovar Typhimurium.

PubMed

Ahmad, Irfan; Rouf, Syed Fazle; Sun, Lei; Cimdins, Annika; Shafeeq, Sulman; Le Guyon, Soazig; Schottkowski, Marco; Rhen, Mikael; Römling, Ute

2016-10-19

Cellulose, a 1,4 beta-glucan polysaccharide, is produced by a variety of organisms including bacteria. Although the production of cellulose has a high biological, ecological and economical impact, regulatory mechanisms of cellulose biosynthesis are mostly unknown. Family eight cellulases are regularly associated with cellulose biosynthesis operons in bacteria; however, their function is poorly characterized. In this study, we analysed the role of the cellulase BcsZ encoded by the bcsABZC cellulose biosynthesis operon of Salmonella enterica serovar Typhimurium (S. Typhimurium) in biofilm related behavior. We also investigated the involvement of BcsZ in pathogenesis of S. Typhimurium including a murine typhoid fever infection model. In S. Typhimurium, cellulase BcsZ with a putative periplasmic location negatively regulates cellulose biosynthesis. Moreover, as assessed with a non-polar mutant, BcsZ affects cellulose-associated phenotypes such as the rdar biofilm morphotype, cell clumping, biofilm formation, pellicle formation and flagella-dependent motility. Strikingly, although upregulation of cellulose biosynthesis was not observed on agar plate medium at 37 °C, BcsZ is required for efficient pathogen-host interaction. Key virulence phenotypes of S. Typhimurium such as invasion of epithelial cells and proliferation in macrophages were positively regulated by BcsZ. Further on, a bcsZ mutant was outcompeted by the wild type in organ colonization in the murine typhoid fever infection model. Selected phenotypes were relieved upon deletion of the cellulose synthase BcsA and/or the central biofilm activator CsgD. Although the protein scaffold has an additional physiological role, our findings indicate that the catalytic activity of BcsZ effectively downregulates CsgD activated cellulose biosynthesis. Repression of cellulose production by BcsZ subsequently enables Salmonella to efficiently colonize the host.

Survey on breast cancer patients in China toward breast-conserving surgery.

PubMed

Zhang, Li; Jiang, Ming; Zhou, Yi; Du, Xiao-Bo; Yao, Wen-Xiu; Yan, Xi; Jiang, Yu; Zou, Li-Qun

2012-05-01

We sought to investigate attitudes toward breast-conserving therapy (BCS) in early-stage breast cancer (EBC) patients from P. R. China and assess the factors influencing their decision. There exists geographical difference in decision to perform mastectomy or BCS for EBC patients. To date, there has been no report on attitudes toward BCS or factors influencing the surgical choice in mainland China. A structured questionnaire was delivered to 1800 EBC patients. The questionnaire elicited information about general patients' characteristics, attitudes toward BCS, the roles of doctors and spouses, the levels of understanding of BCS, and the reasons for their preferences. Of 1590 participants, only 7.3% anticipated BCS and this was significantly associated with patient age, income, occupation, martial status, education, levels of self-understanding of the disease, and doctors' and spouses' suggestions (P<0.05). Approximately 70% of doctors (71.0%) and 40% spouses (39.6%) advised patients not to conserve their breasts. Although the percentage of patients endorsing BCS was higher than that of those opposing it (43.7 vs 15.1%) and more patient believed BCS was beneficial for women (39.2%), even if given another opportunity, only 32.5% of patients preferred to choose it. Moreover, the level of understanding BCS among patients is low (well-known: less-known: never-heard, 2.3 vs 47.4 vs 13.3%). These results suggested that Chinese EBC patients lack accurate and comprehensive understanding of BCS. More efforts are needed to educate breast cancer patients in mainland China toward BCS. Copyright © 2011 John Wiley & Sons, Ltd.

Bleaching effects of massecuite on some properties of crystallized sugar beet and milk chocolate bars produced.

PubMed

Sadjadi, F Seyed; Honarvar, M; Kalbasi-Ashtari, A; Motaghian, P

2018-04-01

Four kinds of bleached, unbleached, second and third crystal sugars (BCS, UCS, SCS and TCS) were made from different massecuites in a sugar-beet factory, and their physiochemical (polarization, invert sugar, colorants, pH, ash and SO 2 ), microbiological and functional properties were measured. While the polarization of UCS, SCS and TCS were lower than BCS; their invert sucrose, colorants, pH and ash contents were significantly higher than BCS. The phenols and betaine of BCS, UCS, SCS, and TCS were 144, 401, 384 and 673 (mg/100 g); and 244, 791, 4662, and 6589 (mg/100 g); respectively. Whereas the phenol of milk chocolate bars (MCB) made with UCS, SCS, and TCS were only 10% higher than MCB completed with BCS; their betaine contents were substantially (up to 16 times) higher than the ones finished with BCS. Sensory evaluation showed that the MCB prepared with three sugars including UCS, SCS and TCS had significantly higher glossiness, brittleness, flavor and mouth feel than those made with BCS. The greater colorants, ash content and inverted sugars of UCS, SCS and TCS (in comparison with BCS) made considerable improvements in the glossiness, flavor and brittleness of MCB, respectively. BCS had 8 ppm of toxic sulfur; whereas, UCS, SCS and TCS had no detectable sulfur and significantly higher beneficial copper content than BCS. No pathogenic microorganism were detected in UCS, SCS, TCS or their subsequent MCB. Our results highly recommend using UCS, SCS and TCS instead of BCS in food products (such as MCB) due to their higher health benefits.

Crystallographic snapshot of cellulose synthesis and membrane translocation.

PubMed

Morgan, Jacob L W; Strumillo, Joanna; Zimmer, Jochen

2013-01-10

Cellulose, the most abundant biological macromolecule, is an extracellular, linear polymer of glucose molecules. It represents an essential component of plant cell walls but is also found in algae and bacteria. In bacteria, cellulose production frequently correlates with the formation of biofilms, a sessile, multicellular growth form. Cellulose synthesis and transport across the inner bacterial membrane is mediated by a complex of the membrane-integrated catalytic BcsA subunit and the membrane-anchored, periplasmic BcsB protein. Here we present the crystal structure of a complex of BcsA and BcsB from Rhodobacter sphaeroides containing a translocating polysaccharide. The structure of the BcsA-BcsB translocation intermediate reveals the architecture of the cellulose synthase, demonstrates how BcsA forms a cellulose-conducting channel, and suggests a model for the coupling of cellulose synthesis and translocation in which the nascent polysaccharide is extended by one glucose molecule at a time.

BcsA and BcsB form the catalytically active core of bacterial cellulose synthase sufficient for in vitro cellulose synthesis.

PubMed

Omadjela, Okako; Narahari, Adishesh; Strumillo, Joanna; Mélida, Hugo; Mazur, Olga; Bulone, Vincent; Zimmer, Jochen

2013-10-29

Cellulose is a linear extracellular polysaccharide. It is synthesized by membrane-embedded glycosyltransferases that processively polymerize UDP-activated glucose. Polymer synthesis is coupled to membrane translocation through a channel formed by the cellulose synthase. Although eukaryotic cellulose synthases function in macromolecular complexes containing several different enzyme isoforms, prokaryotic synthases associate with additional subunits to bridge the periplasm and the outer membrane. In bacteria, cellulose synthesis and translocation is catalyzed by the inner membrane-associated bacterial cellulose synthase (Bcs)A and BcsB subunits. Similar to alginate and poly-β-1,6 N-acetylglucosamine, bacterial cellulose is implicated in the formation of sessile bacterial communities, termed biofilms, and its synthesis is likewise stimulated by cyclic-di-GMP. Biochemical studies of exopolysaccharide synthesis are hampered by difficulties in purifying and reconstituting functional enzymes. We demonstrate robust in vitro cellulose synthesis reconstituted from purified BcsA and BcsB proteins from Rhodobacter sphaeroides. Although BcsA is the catalytically active subunit, the membrane-anchored BcsB subunit is essential for catalysis. The purified BcsA-B complex produces cellulose chains of a degree of polymerization in the range 200-300. Catalytic activity critically depends on the presence of the allosteric activator cyclic-di-GMP, but is independent of lipid-linked reactants. Our data reveal feedback inhibition of cellulose synthase by UDP but not by the accumulating cellulose polymer and highlight the strict substrate specificity of cellulose synthase for UDP-glucose. A truncation analysis of BcsB localizes the region required for activity of BcsA within its C-terminal membrane-associated domain. The reconstituted reaction provides a foundation for the synthesis of biofilm exopolysaccharides, as well as its activation by cyclic-di-GMP.

A Negative Regulator of Cellulose Biosynthesis, bcsR, Affects Biofilm Formation, and Adhesion/Invasion Ability of Cronobacter sakazakii.

PubMed

Gao, Jian-Xin; Li, Ping; Du, Xin-Jun; Han, Zhong-Hui; Xue, Rui; Liang, Bin; Wang, Shuo

2017-01-01

Cronobacter sakazakii is an important foodborne pathogen that causes neonatal meningitis and sepsis, with high mortality in neonates. However, very little information is available regarding the pathogenesis of C. sakazakii at the genetic level. In our previous study, a cellulose biosynthesis-related gene ( bcsR ) was shown to be involved in C. sakazakii adhesion/invasion into epithelial cells. In this study, the detailed functions of this gene were investigated using a gene knockout technique. A bcsR knockout mutant (Δ bcsR ) of C. sakazakii ATCC BAA-894 showed decreased adhesion/invasion (3.9-fold) in human epithelial cell line HCT-8. Biofilm formation by the mutant was reduced to 50% of that exhibited by the wild-type (WT) strain. Raman spectrometry was used to detect variations in biofilm components caused by bcsR knockout, and certain components, including carotenoids, fatty acids, and amides, were significantly reduced. However, another biofilm component, cellulose, was increased in Δ bcsR , suggesting that bcsR negatively affects cellulose biosynthesis. This result was also verified via RT-PCR, which demonstrated up-regulation of five crucial cellulose synthesis genes ( bcsA, B, C, E, Q ) in Δ bcsR . Furthermore, the expression of other virulence or biofilm-related genes, including flagellar assembly genes ( fliA, C, D ) and toxicity-related genes ( ompA, ompX, hfq ), was studied. The expression of fliC and ompA in the Δ bcsR mutant was found to be remarkably reduced compared with that in the wild-type and the others were also affected excepted ompX . In summary, bcsR is a negative regulator of cellulose biosynthesis but positively regulates biofilm formation and the adhesion/invasion ability of C. sakazakii .

BcsA and BcsB form the catalytically active core of bacterial cellulose synthase sufficient for in vitro cellulose synthesis

PubMed Central

Omadjela, Okako; Narahari, Adishesh; Strumillo, Joanna; Mélida, Hugo; Mazur, Olga; Bulone, Vincent; Zimmer, Jochen

2013-01-01

Cellulose is a linear extracellular polysaccharide. It is synthesized by membrane-embedded glycosyltransferases that processively polymerize UDP-activated glucose. Polymer synthesis is coupled to membrane translocation through a channel formed by the cellulose synthase. Although eukaryotic cellulose synthases function in macromolecular complexes containing several different enzyme isoforms, prokaryotic synthases associate with additional subunits to bridge the periplasm and the outer membrane. In bacteria, cellulose synthesis and translocation is catalyzed by the inner membrane-associated bacterial cellulose synthase (Bcs)A and BcsB subunits. Similar to alginate and poly-β-1,6 N-acetylglucosamine, bacterial cellulose is implicated in the formation of sessile bacterial communities, termed biofilms, and its synthesis is likewise stimulated by cyclic-di-GMP. Biochemical studies of exopolysaccharide synthesis are hampered by difficulties in purifying and reconstituting functional enzymes. We demonstrate robust in vitro cellulose synthesis reconstituted from purified BcsA and BcsB proteins from Rhodobacter sphaeroides. Although BcsA is the catalytically active subunit, the membrane-anchored BcsB subunit is essential for catalysis. The purified BcsA-B complex produces cellulose chains of a degree of polymerization in the range 200–300. Catalytic activity critically depends on the presence of the allosteric activator cyclic-di-GMP, but is independent of lipid-linked reactants. Our data reveal feedback inhibition of cellulose synthase by UDP but not by the accumulating cellulose polymer and highlight the strict substrate specificity of cellulose synthase for UDP-glucose. A truncation analysis of BcsB localizes the region required for activity of BcsA within its C-terminal membrane-associated domain. The reconstituted reaction provides a foundation for the synthesis of biofilm exopolysaccharides, as well as its activation by cyclic-di-GMP. PMID:24127606

Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes

PubMed Central

Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

2012-01-01

AIMS To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. METHODS A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. RESULTS No significant difference in the ‘post/pre surgery oral drug exposure ratio’ (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as ‘solubility limited’ displayed an overall reduction as compared with ‘freely soluble’ compounds, as well as an unaltered and increased ppR. CONCLUSION Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. PMID:22463107

Novel high/low solubility classification methods for new molecular entities.

PubMed

Dave, Rutwij A; Morris, Marilyn E

2016-09-10

This research describes a rapid solubility classification approach that could be used in the discovery and development of new molecular entities. Compounds (N=635) were divided into two groups based on information available in the literature: high solubility (BDDCS/BCS 1/3) and low solubility (BDDCS/BCS 2/4). We established decision rules for determining solubility classes using measured log solubility in molar units (MLogSM) or measured solubility (MSol) in mg/ml units. ROC curve analysis was applied to determine statistically significant threshold values of MSol and MLogSM. Results indicated that NMEs with MLogSM>-3.05 or MSol>0.30mg/mL will have ≥85% probability of being highly soluble and new molecular entities with MLogSM≤-3.05 or MSol≤0.30mg/mL will have ≥85% probability of being poorly soluble. When comparing solubility classification using the threshold values of MLogSM or MSol with BDDCS, we were able to correctly classify 85% of compounds. We also evaluated solubility classification of an independent set of 108 orally administered drugs using MSol (0.3mg/mL) and our method correctly classified 81% and 95% of compounds into high and low solubility classes, respectively. The high/low solubility classification using MLogSM or MSol is novel and independent of traditionally used dose number criteria. Copyright © 2016 Elsevier B.V. All rights reserved.

Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

PubMed

Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-02-01

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Variation in sorption of propiconazole with biochars: The effect of temperature, mineral, molecular structure, and nano-porosity

USDA-ARS?s Scientific Manuscript database

Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars (PLABs) and animal manure-derived biochars (ANIBs) obtained at three heating treatment temperatures (HTTs) at 300, 450 and 600 degrees Celsius (denoted as BCs300, BCs450, and BCs600) and their corresponding de-ashed BCs450 ...

Knowledge, attitudes, and behaviour regarding breast cancer screening among women from different socio-economic regions in southwest China: a cross-sectional study.

PubMed

Huang, Yuan; Zhou, Ke; Li, Hui; Wang, Anrong; Li, Jiayuan; Pang, Yi; Wang, Qiong; Huang, Rong; Fu, Liang; Kang, Min; Ning, Ping; Yuan, Ping

2011-01-01

In most developed countries, breast cancer screening (BCS) is a well-established practice which is widely accepted by women. In contrast, national BCS projects in China were only launched in the last two years, so little is known about their public response. We surveyed 1,162 Chinese women from different socio-economic regions in Sichuan Province to assess participants' knowledge, attitudes, and behaviour regarding BCS. ANOVA/t-test, Chi-square test, SNK test, and covariance analyses were used to compare subgroups and a multinomial logistic regression model was adopted to examine factors associated with BCS attendance. Statistically significant differences in scores of BCS knowledge were seen across regions. Most women from all four regions were interested in knowing the risk factors for (1,053, 90.6%) and means of prevention (912, 78.5%) of breast cancer. Eight hundred thirty-seven (72.0%) women expressed willingness to pay extra insurance fees when young in exchange for reimbursement for cancer screening when they reached the age at which screening is recommended. Approval of primary medical institutions was generally low. Regional socio-economic level, work status, and education were strong predictors of BCS attendance. To eliminate geographic disparities and raise the participation rate of BCS, future health education should be adjusted to local conditions and strengthened for women in under-developed regions. Incorporating BCS into a regular program of community-based prevention of chronic non-communicable diseases, and increasing medical insurance funds to cover BCS, especially in rural areas, may be effective means to increase BCS attendance.

Development of the Cancer Survivor Profile-Breast Cancer (CSPro-BC) app: patient and nurse perspectives on a new navigation tool.

PubMed

Gehrke, Amanda; Lee, Sukhyung Steve; Hilton, Karrie; Ganster, Barbara; Trupp, Rebecca; McCullough, Corinne; Mott, Elizabeth; Feuerstein, Michael

2018-06-01

Despite advancements in care, cancer survivors continue to report unmet needs following active cancer treatment. The Cancer Survivor Profile-Breast Cancer (CSPro-BC) application (app) was developed to help address these needs, using breast cancer survivors (BCS) as a pilot group. This paper describes the app development, BCS and nurse perceptions of the app, and changes made based on this feedback. The CSPro-BC app was developed for use on an iPad and includes (1) administration of a 15-20-min survey assessing 18 needs, (2) generation of a profile of needs, relative to a reference group of BCS (median 2 years post-treatment), and (3) provision of problem-specific online resources. Perceptions of the app were evaluated using both quantitative and qualitative approaches. Feedback was elicited from nurse navigators and BCS. BCS were recruited until the point of saturation. BCS (N = 11) were middle-aged and a median of 2.4 months post active treatment. Structured questionnaires indicated the following: survey covered meaningful problem areas, profile display was clear, and nurse's involvement was helpful. Follow-up interviews (2 weeks later) revealed that BCS shared their profile with others, but most BCS did not use the resources and those who did thought there were too many. Nurses (N = 3) said the app increased appointment time, but prompted them to discuss areas often not covered in typical BCS follow-up. Feedback by end users directly informed revision of the app. The CSPro-BC app has been optimized based on BCS feedback.

The effects of mindfulness-based stress reduction on objective and subjective sleep parameters in women with breast cancer: a randomized controlled trial.

PubMed

Lengacher, Cecile A; Reich, Richard R; Paterson, Carly L; Jim, Heather S; Ramesar, Sophia; Alinat, Carissa B; Budhrani, Pinky H; Farias, Jerrica R; Shelton, Melissa M; Moscoso, Manolete S; Park, Jong Y; Kip, Kevin E

2015-04-01

The purpose of this study was to investigate the effects of mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)) on multiple measures of objective and subjective sleep parameters among breast cancer survivors (BCS). Data were collected using a two-armed randomized controlled design among BCS enrolled in either a 6-week MBSR(BC) program or a usual care (UC) group with a 12-week follow-up. The present analysis is a subset of the larger parent trial (ClinicalTrials.gov Identifier: NCT01177124). Seventy-nine BCS participants (mean age 57 years), stages 0-III, were randomly assigned to either the formal (in-class) 6-week MBSR(BC) program or UC. Subjective sleep parameters (SSP) (i.e., sleep diaries and the Pittsburgh Sleep Quality Index (PSQI)) and objective sleep parameters (OSP) (i.e., actigraphy) were measured at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) or UC program. Results showed indications of a positive effect of MBSR(BC) on OSP at 12 weeks on sleep efficiency (78.2% MBSR(BC) group versus 74.6% UC group, p = 0.04), percent of sleep time (81.0% MBSR(BC) group versus 77.4% UC group, p = 0.02), and less number waking bouts (93.5 in MBSR(BC) group versus 118.6 in the UC group, p < 0.01). Small nonsignificant improvements were found in SSP in the MBSR(BC) group from baseline to 6 weeks (PSQI total score, p = 0.09). No significant relationship was observed between minutes of MBSR(BC) practice and SSP or OSP. These data suggest that MBSR(BC) may be an efficacious treatment to improve objective and subjective sleep parameters in BCS. Copyright © 2014 John Wiley & Sons, Ltd.

IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites.

PubMed

Hadjithomas, Michalis; Chen, I-Min Amy; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Szeto, Ernest; Huang, Jinghua; Reddy, T B K; Cimermančič, Peter; Fischbach, Michael A; Ivanova, Natalia N; Markowitz, Victor M; Kyrpides, Nikos C; Pati, Amrita

2015-07-14

In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of "big" genomic data for discovering small molecules. IMG-ABC relies on IMG's comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve as the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC's focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in Alphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG's extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world. Copyright © 2015 Hadjithomas et al.

Effects of precalving body condition score and prepartum feeding level on production, reproduction, and health parameters in pasture-based transition dairy cows.

PubMed

Roche, J R; Meier, S; Heiser, A; Mitchell, M D; Walker, C G; Crookenden, M A; Riboni, M Vailati; Loor, J J; Kay, J K

2015-10-01

Precalving feeding level alters postcalving energy balance, dry matter intake, the liver and adipose tissue transcriptome, hepatic lipidosis, and the risk of metabolic diseases in both high-production cows consuming total mixed rations and moderate-production cows grazing pasture. We hypothesized that the reported benefits of a controlled restriction before calving are dependent on precalving body condition score (BCS): low BCS animals would not benefit from reduced feeding levels precalving, but high BCS cows would have metabolic and immunomodulatory profiles indicative of an improved health status. One hundred sixty-one days before calving, 150 cows were allocated randomly to 1 of 6 treatment groups (n = 25) in a 2 × 3 factorial arrangement: 2 precalving BCS categories (4.0 and 5.0; based on a 10-point scale: BCS4 and BCS5, respectively) and 3 levels of energy intake during the 3 wk preceding calving (75, 100, and 125% of estimated requirements). Cows in the BCS4 and BCS5 groups were managed through late lactation to ensure that target calving BCS was achieved at dry off. Cows were then fed to maintain this BCS target until 3 wk before expected calving date, at which point they were managed within their allotted precalving energy intake treatments by offering different allowances of fresh pasture/cow per day. Milk production, body weight, and BCS were measured weekly; blood was sampled weekly before and after calving and on d 0, 1, 2, 3, and 4 relative to calving. Aspirated plasma was assayed for nonesterified fatty acids, β-hydroxybutyrate, total protein, albumin, cholesterol, haptoglobin, IL-1β, IL-6, total antioxidant capacity, and reactive oxygen species. Liver was sampled wk 1, 2, and 4 postcalving for triacylglycerol analysis. Results confirm that precalving BCS and precalving feeding level have both independent and interdependent effects on production and health characteristics of transition dairy cows. Irrespective of precalving BCS, a controlled restriction precalving reduced the net release of nonesterified fatty acids from adipose tissue postpartum and increased plasma calcium concentrations, reducing the risk of milk fever. Fatter cows produced more milk but lost more BCS postcalving and had greater blood β-hydroxybutyrate concentrations and increased hepatic lipidosis. In comparison, after calving, indicators of reduced immune competence were accentuated in BCS4 cows subjected to a feed restriction before calving, probably increasing the risk of infectious diseases. It would appear from these results that optimally conditioned cows will benefit from a short-term (2-3 wk) controlled feed restriction (75-90% of requirements), whereas cows in less than optimal condition should be fed to requirements before calving. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Entanglement between pairing and screening in the Gorkov-Melik-Barkhudarov correction to the critical temperature throughout the BCS-BEC crossover

NASA Astrophysics Data System (ADS)

Pisani, L.; Perali, A.; Pieri, P.; Strinati, G. Calvanese

2018-01-01

The problem of the theoretical description of the critical temperature Tc of a Fermi superfluid dates back to the work by Gorkov and Melik-Barkhudarov (GMB), who addressed it for a weakly coupled (dilute) superfluid in what would today be referred to as the (extreme) BCS (weak-coupling) limit of the BCS-BEC crossover. The point made in this context by GMB was that particle-particle (pairing) excitations, which are responsible for superfluidity to occur below Tc, and particle-hole excitations, which give rise to screening also in a normal system, get effectively disentangled from each other in the BCS limit, thus yielding a reduction by a factor of 2.2 of the value of Tc obtained when neglecting screening effects. Subsequent work on this topic, that was aimed at extending the original GMB argument away from the BCS limit with diagrammatic methods, has tout court kept this disentangling between pairing and screening throughout the BCS-BEC crossover, without realizing that the conditions for it to be valid are soon violated away from the BCS limit. Here, we reconsider this problem from a more general perspective and argue that pairing and screening are intrinsically entangled with each other along the whole BCS-BEC crossover but for the BCS limit considered by GMB, with the particle-hole excitations soon transmuting into particle-particle excitations away from this limit. We substantiate our argument by performing a detailed numerical calculation of the GMB diagrammatic contribution suitably extended to the whole BCS-BEC crossover, where the full wave-vector and frequency dependence occurring in the repeated in-medium two-particle scattering is duly taken into account. Our numerical calculations are tested against analytic results available in both the BCS and BEC limits, and the contribution of the GMB diagrammatic term to the scattering length of composite bosons in the BEC limit is highlighted. We calculate Tc throughout the BCS-BEC crossover and find that it agrees quite well with quantum Monte Carlo calculations and experimental data available in the unitarity regime.

Assessment of body fat in the pony: part I. Relationships between the anatomical distribution of adipose tissue, body composition and body condition.

PubMed

Dugdale, A H A; Curtis, G C; Harris, P A; Argo, C Mc

2011-09-01

Evaluation of equine body fat content is important for nutritional and clinical purposes. However, our understanding of total body fat and its regional distribution in the body is sparse. Currently, body fat evaluation relies on the subjective assessment of body condition score (BCS), which has never been validated against 'gold standard' chemical analysis or dissection measurements in ponies. To define the relationships between subjective (BCS), objective (morphometric) indices of body fat and 'gold standard' measurements of actual body composition. BCS and morphometry offer valid, noninvasive methods for determination of body fat in equids. Seven mature (mean ± s.e. 13 ± 3 years, 212 ± 14 kg, BCS 1.25-7/9), Welsh Mountain pony mares, destined for euthanasia (for nonresearch purposes), were used. For all ponies, body mass (BM), BCS and various morphometric measurements were recorded. Following euthanasia, all ponies were systematically dissected. Discrete white adipose tissue (WAT) depots were independently described. Gross, body chemical composition was determined by proximate analyses. Total somatic soft tissues increased linearly (r(2) = 1.00), whereas body WAT content (1-26% live BM) increased exponentially (r(2) = 0.96), with BCS. WAT was equally distributed between internal and external sites in all animals irrespective of BCS. Nuchal fat was a poor predictor of total WAT (r(2) = 0.66). Periorbital WAT did not alter with BCS (r(2) = 0.01). Heart girth:withers height and ultrasonic retroperitoneal fat depth were closely associated with total, chemically-extracted lipid which comprised 1-29% live BM (r(2) = 0.91 and 0.88, respectively). The exponential relationship between BCS and total body WAT/lipid suggests that BCS is unlikely to be a sensitive index of body fat for animals in moderate-obese states. Morphometric measurements (body girths and retroperitonel fat depth) may be useful to augment subjective BCS systems. © 2011 EVJ Ltd.

Effect of body condition and season on yield and quality of in vitro produced bovine embryos.

PubMed

Chrenek, Peter; Kubovičová, Elena; Olexíková, Lucia; Makarevich, Alexander V; Toporcerová, Silvia; Ostró, Alexander

2015-12-01

The aim of our study was to examine the effects of cow's body condition score (BCS; scale 1-5) and season on the quality of bovine in vitro produced embryos. The proportion of good quality oocytes (Q1 and Q2) was higher (P < 0.05) in the BCS 2 (57.60%) and BCS 3 (60.90%) groups compared with the BCS 1 (43.60%) group. There were no statistical differences in embryo cleavage and blastocyst rate among the BCS groups. The highest total cell number (TCN, DAPI stain) of blastocysts (P < 0.05), recorded in BCS 1 (122.27 ± 6.90) in comparison with BCS 2 (101.8 ± 3.60) or BCS 3 (105.44 ± 3.70) groups, was related to higher dead cell (DCI, TUNEL) index in this group (7.07%) when compared with BCS 2 (6.54%) or BCS 3 (6.06%), respectively. The yield of good quality oocytes during spring was lower (P < 0.05) compared with the summer season. There were significant differences (P < 0.05) in maturation and cleavage rates between autumn and summer (73.42%, 76.2% vs. 85.0%, 41.8%, respectively). The highest (P < 0.01) blastocyst rate was noted during spring and summer months. Significant difference (P < 0.05) in the TCN among spring (99.38 ± 3.90), autumn (110.1 ± 4.58) or summer (108.96 ± 3.52) was observed. The highest proportion of embryos with the best (grade I) actin cytoskeleton (phalloidin-TRITC) quality was noted during the summer months. Our results indicate that body condition affects the initial quality of oocytes, but does not affect embryo cleavage, blastocyst rate and actin quality. This finding may suggest that development in vitro can mask the influence of BCS. The season affects yield and quality of blastocysts in the way that the autumn period is more favorable for embryo development.

Assessment of season-dependent body condition scores in relation to faecal glucocorticoid metabolites in free-ranging Asian elephants

PubMed Central

Pokharel, Sanjeeta Sharma; Seshagiri, Polani B.

2017-01-01

Abstract We studied seasonal and annual changes in visual body condition scores (BCSs), and assessed how these scores were related to levels of faecal glucocorticoid metabolites (fGCMs) in free-ranging Asian elephants (Elephas maximus) in the seasonally dry tropical forests of the Mysore and Nilgiri Elephant Reserves in southern India. We assessed the animals’ BCS visually on a scale of 1 to 5; where 1 represents a very thin and 5 represents a very fat elephant. To understand the influence of seasonality on BCS, we sampled the population during dry (n = 398) and wet seasons (n = 255) of 2013 and 2015 while, for annual changes in BCS, we sampled nine free-ranging adult females from different family groups that had been repeatedly sighted over seven years. To evaluate the influence of body condition on fGCM, 307 faecal samples were collected from 261 different elephants and were analysed. As a parameter of adrenocortical activity, and thus stress, fGCM was measured (μg/g) in the ethanol-extracted samples using a group-specific 11-oxoaetiocholanolone EIA (antibody raised against 11-oxoaetiocholanolone-17-CMO:BSA and biotinylated-11-oxoaetiocholanolone as a label). Effect of age and season on BCS in relation to fGCM was also studied. A seasonal shift in BCS was observed as expected, i.e. individuals with low BCS were more frequent during the dry season when compared with the wet season. Concentrations of fGCM were highest in individuals with lowest BCS (BCS 1) and then significantly declined till BCS 3. fGCM levels were almost comparable for BCS 3, 4 and 5. This pattern was more conspicuous in female than in male elephants. Season-dependent BCS, hence, reflect the stress status as measured by fGCM, especially in female Asian elephants. This could be used as an important non-invasive approach to monitor the physiological health of free-ranging elephant populations. PMID:28721215

Transfer of Downy Mildew Resistance from Wild Basil (Ocimum americanum) to Sweet Basil (O. basilicum).

PubMed

Ben-Naim, Yariv; Falach, Lidan; Cohen, Yigal

2018-01-01

Sweet basil (Ocimum basilicum) is susceptible to downy mildew caused by the oomycete foliar pathogen Peronospora belbahrii. No resistant varieties of sweet basil are commercially available. Here, we report on the transfer of resistance gene Pb1 from the highly resistant tetraploid wild basil O. americanum var. americanum (PI 500945, 2n = 4x = 48) to the tetraploid susceptible O. basilicum 'Sweet basil' (2n = 4x = 48). F1 progeny plants derived from the interspecific hybridization PI 500945 × Sweet basil were resistant, indicating that the gene controlling resistance (Pb1) is dominant, but sterile due to the genetic distance between the parents. Despite their sterility, F1 plants were pollinated with the susceptible parent and 115 first backcross generation to the susceptible parent (BCs1) embryos were rescued in vitro. The emerging BCs1 plants segregated, upon inoculation, 5:1 resistant/susceptible, suggesting that resistance in F1 was controlled by a pair of dominant genes (Pb1A and Pb1A'). Thirty-one partially fertile BCs1 plants were self-pollinated to obtain BCs1-F2 or were backcrossed to Sweet basil to obtain the second backcross generation to the susceptible parent (BCs2). In total, 1 BCs1-F2 and 22 BCs2 progenies were obtained. The BCs1-F2 progeny segregated 35:1 resistant/susceptible, as expected from a tetraploid parent with two dominant resistant genes. The 22 BCs2 progenies segregated 1:1 resistant/susceptible (for a BCs1 parent that carried one dominant gene for resistance) or 5:1 (for a BCs1 parent that carried two dominant genes for resistance) at a ratio of 4:1. The data suggest that a pair of dominant genes (Pb1A and Pb1A') residing on a two homeologous chromosomes is responsible for resistance of PI 500945 against P. belbahrii.

The pattern of LH secretion and the ovarian response to the 'ram effect' in the anoestrous ewe is influenced by body condition but not by short-term nutritional supplementation.

PubMed

Scaramuzzi, R J; Oujagir, L; Menassol, J-B; Freret, S; Piezel, A; Brown, H M; Cognié, J; Fabre Nys, C

2014-10-01

In sheep, the 'ram effect' induces out-of-season fertility and good nutrition increases prolificacy. This experiment determined if fatness or short-term nutritional supplementation modified the response to the 'ram effect'. A group of 48 Île-de-France ewes were fed diets that produced groups with body-condition scores (BCS) of >3.0 and <2.0. Within each BCS group animals were supplemented daily with 500g of lupins from Day -5 to Day 0 (ram introduction) resulting in four groups: low BCS, supplemented (n=7) and non-supplemented (n=8) and high BCS, supplemented (n=12) and non-supplemented (n=11). The blood concentrations of glucose and insulin and the LH response to gonadotrophin-releasing hormone (GnRH) were determined. After the 'ram effect' the pattern of LH pulsatility, the LH surge and ovarian responses were analysed. Low BCS ewes had lower glucose and insulin (P<0.001) and supplementation increased both (P≤0.001). The increase in LH induced by GnRH was reduced in low BCS ewes (P=0.015) but it was not affected by supplementation. Similarly, LH pulsatility was reduced in low BCS ewes (P<0.05). The LH surge and ovarian cyclicity were not affected but the follow-up cycle was delayed (P=0.034) and progesterone was reduced (P=0.029) in low BCS ewes. There was an effect of BCS on ovulation rate (P<0.05). These results show that the BCS can modify the response to the 'ram effect' and that supplementation has little effect on this response.

Associations among body condition score, body weight, and reproductive performance in seasonal-calving dairy cattle.

PubMed

Roche, J R; Macdonald, K A; Burke, C R; Lee, J M; Berry, D P

2007-01-01

The objective of the present study was to identify and quantify relationships between body condition score (BCS) and body weight (BW) in dairy cows with reproduction variables in pasture-based, seasonal-calving dairy herds. Over 2,500 lactation records from 897 spring-calving Holstein-Friesian dairy cows were used in the analyses. Eleven BCS- and 11 BW-related variables were generated, including observations at calving, nadir, planned start of mating (PSM), and first service, as well as days to nadir and the amount and rate of change between periods. The binary reproductive variables were cycling by PSM, mated in the first 21 d from PSM, pregnant to first service, and pregnant in the first 21, 42, and 84 d of the seasonal mating period. Generalized estimating equations were used to identify BCS and BW variables that significantly affected the probability of a successful reproductive outcome. After adjusting for the fixed effect of year of calving, parity (for cycling by PSM only), and the interval from calving to either first service or PSM, reproductive performance was found to be significantly affected by BW or BCS at key points, and by BCS and BW change during lactation. All reproductive response measures were negatively affected when BCS and BW measures indicated an increased severity and duration of the postpartum negative energy balance. In particular, cycling by PSM was positively associated with calving BCS, whereas pregnancy at 21, 42, and 84 d post-PSM were positively associated with nadir BCS and BW gain post-PSM, and negatively associated with BCS loss between calving and nadir. The results highlight the important role that BCS and BW loss has on reproductive performance, especially in seasonal-calving dairy systems because of the short period between calving and PSM.

Breast cancer survivors' perceived medical communication competence and satisfaction with care at the end of treatment.

PubMed

Brédart, Anne; Kop, Jean-Luc; Fiszer, Chavie; Sigal-Zafrani, Brigitte; Dolbeault, Sylvie

2015-12-01

Information is a care priority in most breast cancer survivors (BCS). We assessed whether BCS information needs at 8 months after hospital cancer treatment could be related to their age, education level, perceived medical communication competence, satisfaction with care, attachment style, and self-esteem. Of 426 BCS approached during the last week of treatment (T1), 85% completed the Medical Communication Competence Scale, European Organisation for Research and Treatment of Cancer Satisfaction with Care Questionnaire, Rosenberg's Self-Esteem Scale and Experiences in Close Relationships Scale. The Hospital Anxiety and Depression Scale and the Supportive Care Needs Survey were completed at T1 and again 8 months later (T2) with a 66% (n = 283) response rate. Baseline respondents' median (range) age was 56 years (23-86 years). Information needs decreased over time, although some persisted. Multivariate regression analyses evidenced overall higher information needs at T2 in younger BCS and in those dissatisfied with the information provided at T1. Specifically, in younger BCS, higher information needs were related to lower satisfaction with doctors' availability, and in older BCS, they were related to higher self-perceived competence in information giving, lower self-perceived competence in information seeking, and lower satisfaction with doctors' information provision. Psychological distress was strongly related to information needs. Education, BCS attachment style, and self-esteem were not associated with information needs. In order to enhance supportive care for BCS, younger BCS should be provided with more time to address all their concerns and older BCS should be encouraged to express their specific desires for information. Copyright © 2015 John Wiley & Sons, Ltd.

Dissolution enhancement of chlorzoxazone using cogrinding technique

PubMed Central

Raval, Mihir K.; Patel, Jaydeep M.; Parikh, Rajesh K.; Sheth, Navin R.

2015-01-01

Purpose: The aim of the present work was to improve rate of dissolution and processing parameters of BCS class II drug, chlorzoxazone using cogrinding technique in the presence of different excipients as a carrier. Materials and Methods: The drug was coground with various carriers like polyethylene glycol (PEG 4000), hydroxypropyl methylcellulose (HPMC) E50LV, polyvinylpyrrolidone (PVP)K30, Kaolin and Neusilin US2 using ball mill, where only PEG 4000 improved dissolution rate of drug by bringing amorphization in 1:3 ratio. The coground mixture after 3 and 6 h was evaluated for various analytical, physicochemical and mechanical parameters. Results: The analysis showed conversion of Chlorzoxazone from its crystalline to amorphization form upon grinding with PEG 4000. Coground mixture as well as its directly compressed tablet showed 2.5-fold increment in the dissolution rate compared with pure drug. Directly compressible tablets prepared from pure drug required a large quantity of microcrystalline cellulose (MCC) during compression. The coground mixture and formulation was found stable in nature even after storage (40°C/75% relative humidity). Conclusions: Cogrinding can be successfully utilized to improve the rate of dissolution of poorly water soluble drugs and hence bioavailability. PMID:26682195

Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug.

PubMed

Morgen, Michael; Bloom, Corey; Beyerinck, Ron; Bello, Akintunde; Song, Wei; Wilkinson, Karen; Steenwyk, Rick; Shamblin, Sheri

2012-02-01

To demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug. Amorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans. A physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water. Drug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.

Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.

PubMed

Lavra, Zênia Maria Maciel; Pereira de Santana, Davi; Ré, Maria Inês

2017-01-01

Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus ® ) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus ® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus ® , when protected from moisture.

In vitro biphasic dissolution tests and their suitability for establishing in vitro-in vivo correlations: A historical review.

PubMed

Pestieau, Aude; Evrard, Brigitte

2017-05-01

For many decades, one of the most critical issues in the pharmaceutical industry has been the poor solubility of some drugs. Indeed, a prerequisite for drug absorption is the presence of dissolved drug at the absorption site and this can be challenging for compounds with low aqueous solubility such as BCS class II (low solubility, high permeability) and IV (low solubility, low permeability) compounds. If the development of oral delivery formulations of these compounds is frequently challenging to formulation scientists in the pharmaceutical industry, the in vitro evaluation of these new formulations is also a great challenge. One alternative approach to overcome the problems encountered with conventional dissolution methods is the use of biphasic dissolution systems. This review provides an overview of the origin and the evolution over time of the biphasic systems and the growing interest among scientists regarding their suitability for establishing in vitro-in vivo correlations. The evolution of these systems and their applications from the 1960s to the present day, such as in system variants and improvements, analysis of complex formulations, discriminatory power, bio-relevance, precipitation and supersaturation visualization, etc. will be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Solubilizing properties of new surface-active agents, products of catalytic oxyethylation of cholic acid.

PubMed

Kołodziejczyk, Michał Krzysztof; Nachajski, Michal Jakub; Lukosek, Marek; Zgoda, Marian Mikołaj

2013-01-01

Solubilizing properties of aqueous solutions of a series of surface-active agents, products of oxyethylation of cholic acid, were examined in the present study. The content of oxyethylated segments determined by means of the 1H NMR method enabled the verification of the molecular mass of surfactants along with the calculation of the structural hydrophilic-lipophilic balance (HLB), the solubility parameter delta1/2, and the required solubility level of balance HLB(R). Viscosimetric measurements enabled the calculation of the limiting viscosity number, the content-average molecular mass, the effective volume, the hydrodynamic radius of the surfactant micelle and their equilibrium adducts with rutin, diclofenac and loratadine (BCS Class II and III). By means of the spectrophotometric method (UV) the amount of the solubilized diclofenac, loratadine and rutin (rutoside) was determined in the equilibrium system (saturated solution) in the environment of aqueous solutions of cholic acid derivatives of n(TE) = 20-70. The obtained results serve as a basis for determining the solubilization mechanism of lipophilic therapeutic products and indirectly for estimating the influence of the above process on pharmaceutical as well as biological availability of a micellar adduct from model drug forms (Lindbladt lithogenolitic index).

Ad libitum Pasture Feeding in Late Pregnancy Does Not Improve the Performance of Twin-bearing Ewes and Their Lambs.

PubMed

Corner-Thomas, R A; Back, P J; Kenyon, P R; Hickson, R E; Ridler, A L; Stafford, K J; Morris, S T

2015-03-01

The present study evaluated the effect of controlled ryegrass-white clover herbage availability from day 128 until day 142 of pregnancy in comparison to unrestricted availability, on the performance of twin-bearing ewes of varying body condition score (BCS; 2.0, 2.5, or 3.0) and their lambs. It was hypothesised that under conditions of controlled herbage availability, the performance of lambs born to ewes with a greater BCS would be greater than those born to ewes with a lower BCS. During the period that the nutritional regimens were imposed, the pre- and post-grazing herbage masses of the Control regimen (1,070±69 and 801±30 kg dry matter [DM]/ha) were lower than the ad libitum regimen (1,784±69 and 1,333±33 kg DM/ha; p<0.05). The average herbage masses during lactation were 1,410±31 kg DM/ha. Nutritional regimen had no effect on ewe live weight, BCS and back fat depth or on lamb live weight, indices of colostrum uptake, maximal heat production, total litter weight weaned or survival to weaning (p>0.05). The difference in ewe BCSs and back fats observed among body condition groups was maintained throughout pregnancy (p<0.05). At weaning, ewes from the BCS2.0 group had lower BCS and live weight (2.4±0.2, 74.3±2.6 kg) than both the BCS2.5 (2.6±0.2, 78.6±2.4 kg) and BCS3.0 ewes (2.7±0.2, 79.0±2.6 kg; p<0.05), which did not differ (p>0.05). Ewe BCS group had no effect on lamb live weight at birth or weaning or on maximal heat production (p>0.05). Serum gamma glutamyl transferase concentrations of lambs born to BCS3.0 ewes were higher within 36 hours of birth than lambs born to BCS2.0 ewes and BCS2.5 ewes (51.8±1.9 vs 46.5±1.9 and 45.6±1.9 IU/mL, respectively [p<0.05]). There was, however, no effect of ewe body condition on lamb plasma glucose concentration (p>0.05). Lamb survival was the only lamb parameter that showed an interaction between ewe nutritional regimen and ewe BCS whereby survival of lambs born to BCS2.5 and BCS3.0 ewes differed but only within the Control nutritional regimen ewes (p<0.05). These results indicate farmers can provide twin-bearing ewes with pre- and post-grazing ryegrass-white clover herbage covers of approximately 1,100 and 800 kg DM/ha in late pregnancy, provided that herbage covers are 1400 in lactation, without affecting lamb performance to weaning. The present results also indicate that under these grazing conditions, there is little difference in ewe performance within the BCS range of 2.0 to 3.0 and therefore they do not need to be managed separately.

Ad libitum Pasture Feeding in Late Pregnancy Does Not Improve the Performance of Twin-bearing Ewes and Their Lambs

PubMed Central

Corner-Thomas, R. A.; Back, P. J.; Kenyon, P. R.; Hickson, R. E.; Ridler, A. L.; Stafford, K. J.; Morris, S. T.

2015-01-01

The present study evaluated the effect of controlled ryegrass-white clover herbage availability from day 128 until day 142 of pregnancy in comparison to unrestricted availability, on the performance of twin-bearing ewes of varying body condition score (BCS; 2.0, 2.5, or 3.0) and their lambs. It was hypothesised that under conditions of controlled herbage availability, the performance of lambs born to ewes with a greater BCS would be greater than those born to ewes with a lower BCS. During the period that the nutritional regimens were imposed, the pre- and post-grazing herbage masses of the Control regimen (1,070±69 and 801±30 kg dry matter [DM]/ha) were lower than the ad libitum regimen (1,784±69 and 1,333±33 kg DM/ha; p<0.05). The average herbage masses during lactation were 1,410±31 kg DM/ha. Nutritional regimen had no effect on ewe live weight, BCS and back fat depth or on lamb live weight, indices of colostrum uptake, maximal heat production, total litter weight weaned or survival to weaning (p>0.05). The difference in ewe BCSs and back fats observed among body condition groups was maintained throughout pregnancy (p<0.05). At weaning, ewes from the BCS2.0 group had lower BCS and live weight (2.4±0.2, 74.3±2.6 kg) than both the BCS2.5 (2.6±0.2, 78.6±2.4 kg) and BCS3.0 ewes (2.7±0.2, 79.0±2.6 kg; p<0.05), which did not differ (p>0.05). Ewe BCS group had no effect on lamb live weight at birth or weaning or on maximal heat production (p>0.05). Serum gamma glutamyl transferase concentrations of lambs born to BCS3.0 ewes were higher within 36 hours of birth than lambs born to BCS2.0 ewes and BCS2.5 ewes (51.8±1.9 vs 46.5±1.9 and 45.6±1.9 IU/mL, respectively [p<0.05]). There was, however, no effect of ewe body condition on lamb plasma glucose concentration (p>0.05). Lamb survival was the only lamb parameter that showed an interaction between ewe nutritional regimen and ewe BCS whereby survival of lambs born to BCS2.5 and BCS3.0 ewes differed but only within the Control nutritional regimen ewes (p<0.05). These results indicate farmers can provide twin-bearing ewes with pre- and post-grazing ryegrass-white clover herbage covers of approximately 1,100 and 800 kg DM/ha in late pregnancy, provided that herbage covers are 1400 in lactation, without affecting lamb performance to weaning. The present results also indicate that under these grazing conditions, there is little difference in ewe performance within the BCS range of 2.0 to 3.0 and therefore they do not need to be managed separately. PMID:25656209

Quantum quench in a p+ip superfluid: Winding numbers and topological states far from equilibrium

NASA Astrophysics Data System (ADS)

Foster, Matthew S.; Dzero, Maxim; Gurarie, Victor; Yuzbashyan, Emil A.

2013-09-01

We study the nonadiabatic dynamics of a two-dimensional p+ip superfluid following an instantaneous quantum quench of the BCS coupling constant. The model describes a topological superconductor with a nontrivial BCS (trivial BEC) phase appearing at weak- (strong-) coupling strengths. We extract the exact long-time asymptotics of the order parameter Δ(t) by exploiting the integrability of the classical p-wave Hamiltonian, which we establish via a Lax construction. Three different types of asymptotic behavior can occur depending upon the strength and direction of the interaction quench. We refer to these as the nonequilibrium phases {I, II, III}, characterized as follows. In phase I, the order parameter asymptotes to zero due to dephasing. In phase II, Δ→Δ∞, a nonzero constant. Phase III is characterized by persistent oscillations of Δ(t). For quenches within phases I and II, we determine the topological character of the asymptotic states. We show that two different formulations of the bulk topological winding number, although equivalent in the BCS or BEC ground states, must be regarded as independent out of equilibrium. The first winding number Q characterizes the Anderson pseudospin texture of the initial state; we show that Q is generically conserved. For Q≠0, this leads to the prediction of a “gapless topological” state when Δ asymptotes to zero. The presence or absence of Majorana edge modes in a sample with a boundary is encoded in the second winding number W, which is formulated in terms of the retarded Green's function. We establish that W can change following a quench across the quantum critical point. When the order parameter asymptotes to a nonzero constant, the final value of W is well defined and quantized. We discuss the implications for the (dis)appearance of Majorana edge modes. Finally, we show that the parity of zeros in the bulk out-of-equilibrium Cooper-pair distribution function constitutes a Z2-valued quantum number, which is nonzero whenever W≠Q. The pair distribution can in principle be measured using rf spectroscopy in an ultracold-atom realization, allowing direct experimental detection of the Z2 number. This has the following interesting implication: topological information that is experimentally inaccessible in the bulk ground state can be transferred to an observable distribution function when the system is driven far from equilibrium.

Study of effect of variables on particle size of telmisartan nanosuspensions using box-Behnken design.

PubMed

Rao, M R P; Bajaj, A

2014-12-01

Telmisartan, an orally active nonpeptide angiotensin II receptor antagonist is a BCS Class II drug having aqueous solubility of 9.9 µg/ml and hence oral bioavailability of 40%. The present study involved preparation of nanosuspensions by evaporative antisolvent precipitation technique to improve the saturation solubility and dissolution rate of telmisartan. Various stabilizers such as TPGS, PVPK 30, PEG 6000 were investigated of which TPGS was found to provide maximum decrease in particle size and accord greater stability to the nanosuspensions. Box-Behnken design was used to investigate the effect of independent variables like stabilizer concentration, time and speed of stirring on particle size of nanosuspensions. Pharmacodynamic studies using Goldblatt technique were undertaken to evaluate the effect of nano-sizing on the hypotensive effect of the drug. Concentration of TPGS and speed of rotation were found to play an important role in particle size of the nanosuspensions whereas time of stirring displayed an exponential relationship with particle size. Freeze dried nanocrystals obtained from nanosuspension of least particle size were found to have increased saturation solubility of telmisartan in different dissolution media. The reconstituted nanosuspension was found to reduce both systolic and diastolic blood pressure without affecting pulse pressure and heart rate. Statistical tools can be used to identify key process and formulation parameters which play a significant role in controlling the particle size in nanosuspensions. © Georg Thieme Verlag KG Stuttgart · New York.

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

2016-02-01

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

Unravelling the temporal association between lameness and body condition score in dairy cattle using a multistate modelling approach.

PubMed

Lim, P Y; Huxley, J N; Willshire, J A; Green, M J; Othman, A R; Kaler, J

2015-03-01

Recent studies have reported associations between lameness and body condition score (BCS) in dairy cattle, however the impact of change in the dynamics of BCS on both lameness occurrence and recovery is currently unknown. The aim of this longitudinal study was to investigate the effect of change in BCS on the transitions from the non-lame to lame, and lame to non-lame states. A total of 731 cows with 6889 observations from 4 UK herds were included in the study. Mobility score (MS) and body condition score (BCS) were recorded every 13-15 days from July 2010 until December 2011. A multilevel multistate discrete time event history model was built to investigate the transition of lameness over time. There were 1042 non-lame episodes and 593 lame episodes of which 50% (519/1042) of the non-lame episodes transitioned to the lame state and 81% (483/593) of the lame episodes ended with a transition to the non-lame state. Cows with a lower BCS at calving (BCS Group 1 (1.00-1.75) and Group 2 (2.00-2.25)) had a higher probability of transition from non-lame to lame and a lower probability of transition from lame to non-lame compared to cows with BCS 2.50-2.75, i.e. they were more likely to become lame and if lame, they were less likely to recover. Similarly, cows who suffered a greater decrease in BCS (compared to their BCS at calving) had a higher probability of becoming lame and a lower probability of recovering in the next 15 days. An increase in BCS from calving was associated with the converse effect, i.e. a lower probability of cows moving from the non-lame to the lame state and higher probability of transition from lame to non-lame. Days in lactation, quarters of calving and parity were associated with both lame and non-lame transitions and there was evidence of heterogeneity among cows in lameness occurrence and recovery. This study suggests loss of BCS and increase of BCS could influence the risk of becoming lame and the chance of recovery from lameness. Regular monitoring and maintenance of BCS on farms could be a key tool for reducing lameness. Further work is urgently needed in this area to allow a better understanding of the underlying mechanisms behind these relationships. Copyright © 2015 Elsevier B.V. All rights reserved.

Factors that influence awareness of breast cancer screening among Arab women in Qatar: results from a cross sectional survey.

PubMed

Donnelly, Tam Truong; Khater, Al-Hareth Al; Al-Bader, Salha Bujassoum; Al Kuwari, Mohammed Ghaith; Malik, Mariam; Al-Meer, Nabila; Singh, Rajvir; Fung, Tak

2014-01-01

Breast cancer is the most common cancer among women in the State of Qatar. Due to low participation in breast cancer screening (BCS) activities, women in Qatar are often diagnosed with breast cancer at advanced stages of the disease. Findings indicate that low participation rates in BCS activities are significantly related to women's low level of awareness of breast cancer screening. The objectives of this study were to: (1) determine the factors that influence Qatari women's awareness of breast cancer and its screening activities: and (2) to find ways to effectively promote breast cancer screening activities among Arabic speaking women in Qatar. A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) female Qatari citizens and non-Qatari Arabic-speaking residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Outcome measures included participant awareness levels of the most recent national recommended guidelines of BCS, participation rates in BCS activities, and factors related to awareness of BCS activities. While most participants (90.7%) were aware of breast cancer, less than half had awareness of BCS practices (28.9% were aware of breast self-examination and 41.8% of clinical breast exams, while 26.4% knew that mammography was recommended by national screening guidelines. Only 7.6% had knowledge of all three BCS activities). Regarding BCS practice, less than one-third practiced BCS appropriately (13.9% of participants performed breast self-examination (BSE) monthly, 31.3% had a clinical breast exam (CBE) once a year or once every two years, and 26.9% of women 40 years of age or older had a mammogram once every year or two years). Awareness of BCS was significantly related to BCS practice, education level, and receipt of information about breast cancer and/or BCS from a variety of sources, particularly doctors and the media. The low levels of participation rates in BCS among Arab women in this study indicate a strong need to increase awareness of the importance of breast cancer screening in Qatari women. Without this awareness, compliance with the most recent breast cancer screening recommendations in Qatar will remain low. An increased effort to implement mass media and public health campaigns regarding the impact of breast cancer on women's health and the benefits of early detection of breast cancer must be coupled with an enhanced participation of health care providers in delivering this message to Qatar population.

Thrombophilic Genetic Factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin 20210A in Noncirrhotic Portal Vein Thrombosis and Budd-Chiari Syndrome in a Caucasian Population

PubMed Central

D'Amico, Mario; Sammarco, Pietro; Pasta, Linda

2013-01-01

Thrombophilic genetic factors PAI-1, MTHFRC677T, V Leiden 506Q, and Prothrombin 20210A were studied as risk factors in 235 Caucasian subjects: 85 patients with abdominal thrombosis (54 with portal vein thrombosis (PVT) and 31 with Budd-Chiari syndrome (BCS) without liver cirrhosis or hepatocellular carcinoma) and 150 blood bank donors. Seventy-five patients with PVT/BCS showed associated disease or particular clinical status (46 PVT/29 BCS): 37 myeloproliferative neoplasm (20 PVT/17 BCS), 12 abdominal surgery (10 PVT/2 BCS), 10 contraception or pregnancy (6 PVT/4 BCS), 7 abdominal acute disease (6 PVT/1 BCS), and 9 chronic disease (4 PVT/5 BCS); ten patients did not present any association (8 PVT/2 BCS). PAI-14G-4G, MTHFR677TT, and V Leiden 506Q were significantly frequent (OR 95% CI and χ 2 test with P value) in abdominal thrombosis; in these patients PAI-14G-4G and MTHFR677TT distributions deviated from that expected from a population in the Hardy-Weinberg equilibrium (PAI-1: χ 2 = 13.8, P < 0.001; MTHFR677: χ 2 = 7.1, P < 0.01), whereas the equilibrium was respected in healthy controls. V Leiden Q506 and Prothrombin 20210A were in the Hardy-Weinberg equilibrium both in patients with abdominal thrombosis and healthy controls. Our study shows an important role of PAI-14G-4G and MTHFR677TT in abdominal thrombosis without liver cirrhosis or hepatocellular carcinoma. PMID:24455271

Pre-conception energy balance and secondary sex ratio--partial support for the Trivers-Willard hypothesis in dairy cows.

PubMed

Roche, J R; Lee, J M; Berry, D P

2006-06-01

According to the Trivers-Willard hypothesis, maternal condition at or around conception affects the secondary sex ratio in mammals. However, there are little or no data available on indicators of maternal condition in dairy cows on the sex of the resultant offspring. A total of 76,607 body condition score (BCS; scale of 1 to 5) records and 76,611 body weight (BW) records from 3,209 lactations across 1,172 cows were extracted from a research database collated from one research herd between 1986 and 2004, inclusive. Exclusion of multiple births and cows with no information before calving (e.g., nulliparous animals) resulted in 2,029 records with BCS and BW observations from the previous calving, and 2,002 and 1,872 lactations with BCS and BW observations at conception and midgestation, respectively. Change in BCS and BW between calving and conception and between conception and midgestation was calculated per lactation. Generalized estimating equations were used to model the logit of the probability of a male calf, in which cow was included as a repeated effect with a first-order autoregressive correlation structure assumed among records within cow. Of the BCS variables investigated, there was a linear relationship between the logit of the probability of a male calf and BCS change between calving and conception, the rate of BCS change over this period (BCS divided by days in milk), and BCS at the calving event immediately before conception. The birth of a bull calf was 1.85 times more likely in cows that lost no BCS from calving to conception compared with cows that lost one BCS unit from calving to conception. This increase in odds was equivalent to a 14% unit increase in the probability of a male calf (from 54 to 68%). The amount of BW lost between calving and conception and the rate of loss affected the sex of the resultant offspring. Less BW loss or greater BW gain between calving and conception was associated with greater likelihood of a male calf. Results suggested a positive effect of pre-conception BCS and BW change on secondary sex ratio, agreeing with the Trivers-Willard hypothesis that females in good physiological condition are more likely to produce male offspring.

Accounting for energy and protein reserve changes in predicting diet-allowable milk production in cattle.

PubMed

Tedeschi, L O; Seo, S; Fox, D G; Ruiz, R

2006-12-01

Current ration formulation systems used to formulate diets on farms and to evaluate experimental data estimate metabolizable energy (ME)-allowable and metabolizable protein (MP)-allowable milk production from the intake above animal requirements for maintenance, pregnancy, and growth. The changes in body reserves, measured via the body condition score (BCS), are not accounted for in predicting ME and MP balances. This paper presents 2 empirical models developed to adjust predicted diet-allowable milk production based on changes in BCS. Empirical reserves model 1 was based on the reserves model described by the 2001 National Research Council (NRC) Nutrient Requirements of Dairy Cattle, whereas empirical reserves model 2 was developed based on published data of body weight and composition changes in lactating dairy cows. A database containing 134 individually fed lactating dairy cows from 3 trials was used to evaluate these adjustments in milk prediction based on predicted first-limiting ME or MP by the 2001 Dairy NRC and Cornell Net Carbohydrate and Protein System models. The analysis of first-limiting ME or MP milk production without adjustments for BCS changes indicated that the predictions of both models were consistent (r(2) of the regression between observed and model-predicted values of 0.90 and 0.85), had mean biases different from zero (12.3 and 5.34%), and had moderate but different roots of mean square errors of prediction (5.42 and 4.77 kg/d) for the 2001 NRC model and the Cornell Net Carbohydrate and Protein System model, respectively. The adjustment of first-limiting ME- or MP-allowable milk to BCS changes improved the precision and accuracy of both models. We further investigated 2 methods of adjustment; the first method used only the first and last BCS values, whereas the second method used the mean of weekly BCS values to adjust ME- and MP-allowable milk production. The adjustment to BCS changes based on first and last BCS values was more accurate than the adjustment to BCS based on the mean of all BCS values, suggesting that adjusting milk production for mean weekly variations in BCS added more variability to model-predicted milk production. We concluded that both models adequately predicted the first-limiting ME- or MP-allowable milk after adjusting for changes in BCS.

Induction of oxidative DNA damage by mesalamine in the presence of copper: a potential mechanism for mesalamine anticancer activity.

PubMed

Zimmerman, Ryan P; Jia, Zhenquan; Zhu, Hong; Vandjelovic, Nathan; Misra, Hara P; Wang, Jianmin; Li, Yunbo

2011-02-27

Mesalamine is the first line pharmacologic intervention for patients with ulcerative colitis, and recent epidemiologic studies have demonstrated a protective association between therapeutic use of the drug and colorectal carcinoma. However, the mechanism by which this protection is afforded has yet to be elucidated. Because copper is found at higher than normal concentrations in neoplastic cell nuclei and is known to interact with phenolic compounds to generate reactive oxygen species, we investigated whether the reaction of mesalamine/copper was able to induce oxidative DNA strand breaks in φX-174 RF I plasmid DNA, and the various components of the mechanism by which the reaction occurred. Plasmid DNA strand breaks were induced by pharmacologically relevant concentrations of mesalamine in the presence of a micromolar concentration of Cu(II), and damage was inhibited by bathocuproinedisulfonic acid (BCS) and catalase. Further, we showed that the reaction of copper with mesalamine consumed molecular oxygen, which was inhibited by BCS. Electron paramagnetic resonance spectral analysis of the reaction of copper/mesalamine indicated the presence of the hydroxyl radical, which was inhibited by both BCS and catalase. This study demonstrates for the first time that through a copper-redox cycling mechanism, the copper-mediated oxidation of mesalamine is a pro-oxidant interaction that generates hydroxyl radicals which may participate in oxidative DNA damage. These results demonstrate a potential mechanism of the anticancer effects of mesalamine in patients with ulcerative colitis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Genetic parameters for body condition score, body weight, milk yield, and fertility estimated using random regression models.

PubMed

Berry, D P; Buckley, F; Dillon, P; Evans, R D; Rath, M; Veerkamp, R F

2003-11-01

Genetic (co)variances between body condition score (BCS), body weight (BW), milk yield, and fertility were estimated using a random regression animal model extended to multivariate analysis. The data analyzed included 81,313 BCS observations, 91,937 BW observations, and 100,458 milk test-day yields from 8725 multiparous Holstein-Friesian cows. A cubic random regression was sufficient to model the changing genetic variances for BCS, BW, and milk across different days in milk. The genetic correlations between BCS and fertility changed little over the lactation; genetic correlations between BCS and interval to first service and between BCS and pregnancy rate to first service varied from -0.47 to -0.31, and from 0.15 to 0.38, respectively. This suggests that maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in midlactation when the genetic variance for BCS is largest. Selection for increased BW resulted in shorter intervals to first service, but more services and poorer pregnancy rates; genetic correlations between BW and pregnancy rate to first service varied from -0.52 to -0.45. Genetic selection for higher lactation milk yield alone through selection on increased milk yield in early lactation is likely to have a more deleterious effect on genetic merit for fertility than selection on higher milk yield in late lactation.

Accelerated loading evaluation of stabilized BCS layers in pavement performance : tech summary.

DOT National Transportation Integrated Search

2012-03-01

The Louisiana Department of Transportation and Development (LADOTD) began to use blended calcium sulfate (BCS) as : an alternative base material in the 1990s. Raw BCS base without further chemical stabilization can achieve relatively high : strength ...

Body condition score, morphometric measurements and estimation of body weight in mature Icelandic horses in Denmark.

PubMed

Jensen, Rasmus B; Danielsen, Signe H; Tauson, Anne-Helene

2016-10-20

Obesity is related to the development of several diseases like insulin resistance and laminitis in horses. The prevalence of obesity among mature Icelandic horses in Denmark has not been investigated previously. This study aimed to find the prevalence of obesity, to compare body condition score (BCS) based on owner perception with that of an experienced person and to correlate the BCS to body weight (BW) and morphometric measures in a group of mature Icelandic horses in Denmark. A total of 254 Icelandic horses (≥4 years; 140 geldings, 105 mares, 9 stallions) from 46 different farms were included. All horses were assigned a BCS on a scale from 1 to 9 (1 is poor, 5 is moderate and 9 is extremely fat) by their owner and by an experienced person. Two weight tapes were used to assess BW. Girth circumference (GC), neck circumference (NC) and height at withers (HW) were measured, and the GC:HW and NC:HW ratios were calculated. Categorising the horses into four groups, 5.9 % were underweight (BCS 3-4), 70.1 % were optimal (BCS 5-6), 13.8 % were overweight (BCS 7) and 10.2 % were obese (BCS 8-9). The GC:HW and NC:HW ratios increased with increasing BCS, as did the BW estimated with the weight tapes. A GC:HW ratio >1.21 might indicate overweight or obesity in Icelandic horses. Horse owners underestimated the BCS of their horses compared to an experienced person. The results from this study show that 24.0 % of mature Icelandic horses in Denmark are overweight or obese, and that owners tend to underestimate the BCS of their Icelandic horses. The GC:HW ratio might indicate overweight or obesity, however, the ratio for Icelandic horses is different than reported for horses and ponies of other breeds.

Do socioeconomic factors influence breast cancer screening practices among Arab women in Qatar?

PubMed

Donnelly, Tam Truong; Al Khater, Al-Hareth; Al Kuwari, Mohamed Ghaith; Al-Bader, Salha Bujassoum; Al-Meer, Nabila; Abdulmalik, Mariam; Singh, Rajvir; Chaudhry, Sofia; Fung, Tak

2015-01-22

Breast cancer incidence rates are rising in Qatar. Although the Qatari government provides subsidised healthcare and screening programmes that reduce cost barriers for residents, breast cancer screening (BCS) practices among women remain low. This study explores the influence of socioeconomic status on BCS among Arab women in Qatar. A multicentre, cross-sectional quantitative survey was conducted with 1063 Arab women (87.5% response rate) in Qatar from March 2011 to July 2011. Women who were 35 years or older and had lived in Qatar for at least 10 years were recruited from seven primary healthcare centres and women's health clinics in urban and semiurban regions of Qatar. Associations between socioeconomic factors and BCS practice were estimated using χ(2) tests and multivariate logistic regression analyses. Findings indicate that less than one-third of the participants practised BCS appropriately, whereas less than half of the participants were familiar with recent BCS guidelines. Married women and women with higher education and income levels were significantly more likely to be aware of and to practise BCS than women who had lower education and income levels. Findings indicate low levels of awareness and low participation rates in BCS among Arab women in Qatar. Socioeconomic factors influence these women's participation in BCS activities. The strongest predictors for BCS practice are higher education and higher income levels. Additional research is needed to explore the impact of economic factors on healthcare seeking behaviours in the Middle Eastern countries that have a high national gross domestic product where healthcare services are free or heavily subsidised by the government; promotion of BCS and intervention strategies in these countries should focus on raising awareness about breast cancer, the cost and benefit of early screening for this disease, particularly among low-income women. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Do socioeconomic factors influence breast cancer screening practices among Arab women in Qatar?

PubMed Central

Donnelly, Tam Truong; Al Khater, Al-Hareth; Al Kuwari, Mohamed Ghaith; Al-Bader, Salha Bujassoum; Al-Meer, Nabila; Abdulmalik, Mariam; Singh, Rajvir; Chaudhry, Sofia; Fung, Tak

2015-01-01

Objectives Breast cancer incidence rates are rising in Qatar. Although the Qatari government provides subsidised healthcare and screening programmes that reduce cost barriers for residents, breast cancer screening (BCS) practices among women remain low. This study explores the influence of socioeconomic status on BCS among Arab women in Qatar. Setting A multicentre, cross-sectional quantitative survey was conducted with 1063 Arab women (87.5% response rate) in Qatar from March 2011 to July 2011. Women who were 35 years or older and had lived in Qatar for at least 10 years were recruited from seven primary healthcare centres and women's health clinics in urban and semiurban regions of Qatar. Associations between socioeconomic factors and BCS practice were estimated using χ2 tests and multivariate logistic regression analyses. Results Findings indicate that less than one-third of the participants practised BCS appropriately, whereas less than half of the participants were familiar with recent BCS guidelines. Married women and women with higher education and income levels were significantly more likely to be aware of and to practise BCS than women who had lower education and income levels. Conclusions Findings indicate low levels of awareness and low participation rates in BCS among Arab women in Qatar. Socioeconomic factors influence these women's participation in BCS activities. The strongest predictors for BCS practice are higher education and higher income levels. Recommendations Additional research is needed to explore the impact of economic factors on healthcare seeking behaviours in the Middle Eastern countries that have a high national gross domestic product where healthcare services are free or heavily subsidised by the government; promotion of BCS and intervention strategies in these countries should focus on raising awareness about breast cancer, the cost and benefit of early screening for this disease, particularly among low-income women. PMID:25613951

Impacts of parturition and body condition score on glucose uptake capacity of bovine monocyte subsets.

PubMed

Eger, Melanie; Hussen, Jamal; Drong, Caroline; Meyer, Ulrich; von Soosten, Dirk; Frahm, Jana; Daenicke, Sven; Breves, Gerhard; Schuberth, Hans-Joachim

2015-07-15

The peripartal period of dairy cows is associated with a higher incidence of infectious diseases like mastitis or metritis, particularly in high-yielding animals. The onset of lactation induces a negative energy balance and a shift of glucose distribution toward the udder. Glucose is used as primary fuel by monocytes which give rise to macrophages, key cells in the defense against pathogens. The aim of this study was to analyze whether animals with high or low body condition score (BCS) differ in composition and glucose uptake capacities of bovine monocyte subsets. Blood samples were taken from 27 dairy cows starting 42 days before parturition until day 56 after parturition. The cows were allocated to two groups according to their BCS. A feeding regime was applied, in which the BCS high group received higher amounts of concentrate before parturition and concentrate feeding was more restricted in the BCS high group after parturition compared with the BCS low group, to promote postpartal lipolysis and enhance negative energy balance in the BCS high group. Blood cell counts of classical (cM), intermediate (intM) and nonclassical monocytes (ncM) were increased at day 7 after calving. In the BCS low group intM numbers were significantly higher compared to the BCS high group at day 7 after parturition. Within the BCS low group cows suffering from mastitis or metritis showed significantly higher numbers of cM, intM and ncM at day 7 after parturition. Classical monocytes and intM showed similar glucose uptake capacities while values for ncM were significantly lower. Compared with antepartal capacities and irrespective of BCS and postpartal mastitis or metritis, glucose uptake of all monocyte subsets decreased after parturition. In conclusion, whereas glucose uptake capacity of bovine monocyte subsets is altered by parturition, it is not linked to the energy supply of the animals or to postpartal infectious diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Genetic correlations among body condition score, yield, and fertility in first-parity cows estimated by random regression models.

PubMed

Veerkamp, R F; Koenen, E P; De Jong, G

2001-10-01

Twenty type classifiers scored body condition (BCS) of 91,738 first-parity cows from 601 sires and 5518 maternal grandsires. Fertility data during first lactation were extracted for 177,220 cows, of which 67,278 also had a BCS observation, and first-lactation 305-d milk, fat, and protein yields were added for 180,631 cows. Heritabilities and genetic correlations were estimated using a sire-maternal grandsire model. Heritability of BCS was 0.38. Heritabilities for fertility traits were low (0.01 to 0.07), but genetic standard deviations were substantial, 9 d for days to first service and calving interval, 0.25 for number of services, and 5% for first-service conception. Phenotypic correlations between fertility and yield or BCS were small (-0.15 to 0.20). Genetic correlations between yield and all fertility traits were unfavorable (0.37 to 0.74). Genetic correlations with BCS were between -0.4 and -0.6 for calving interval and days to first service. Random regression analysis (RR) showed that correlations changed with days in milk for BCS. Little agreement was found between variances and correlations from RR, and analysis including a single month (mo 1 to 10) of data for BCS, especially during early and late lactation. However, this was due to excluding data from the conventional analysis, rather than due to the polynomials used. RR and a conventional five-traits model where BCS in mo 1, 4, 7, and 10 was treated as a separate traits (plus yield or fertility) gave similar results. Thus a parsimonious random regression model gave more realistic estimates for the (co)variances than a series of bivariate analysis on subsets of the data for BCS. A higher genetic merit for yield has unfavorable effects on fertility, but the genetic correlation suggests that BCS (at some stages of lactation) might help to alleviate the unfavorable effect of selection for higher yield on fertility.

Barriers to breast cancer screening participation among Jordanian and Palestinian American women.

PubMed

Kawar, Lina Najib

2013-02-01

Increasing breast cancer screening (BCS) among diverse women from minority groups is a goal of health care providers and national organizations as a way to help in the early detection and treatment of breast cancer. The purpose of this article is to investigate barriers to BCS encountered by Jordanian and Palestinian women living in the United States (US). Descriptive content analysis of interviews of 107 Jordanian and Palestinian immigrant women provided data on BCS barriers that were thematically analyzed. Data revealed 4 barriers that affect Jordanian and Palestinian immigrant women's participation in BCS: (1) culture-specific barriers such as embarrassment, family relationships, fatalism, and traditional healers consultation; (2) immigration-related barriers (citizenship issues and language); (3) general barriers (including nonparticipation in health screening, stigmatization of cancer, fear, and ignorance about BCS); and (4) irrelevant barriers. Clinicians should be cognizant of the culture, beliefs and practices of Arab Middle Eastern immigrant women and the influence of these factors on their decision to participate in routine BCS. To increase participation in BCS and knowledge of breast cancer, appropriate language and culturally sensitive educational materials should be created and made available to Arab Middle Eastern immigrant women. Copyright © 2012 Elsevier Ltd. All rights reserved.

Accelerated loading evaluation of stabilized BCS layers in pavement performance.

DOT National Transportation Integrated Search

2012-03-01

BCS is short for blended calcium sulfate, a recycled fluorogypsum mixture that has been used in Louisiana as a roadway base for more than a decade. : Without further chemical stabilization, the major concern of using raw BCS as a pavement structural ...

Comparative study of BCS-BEC crossover theories above T{sub c}: The nature of the pseudogap in ultracold atomic Fermi gases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chien, C.-C.; Guo Hao; He Yan

2010-02-15

This article presents a comparison of two finite-temperature BCS-Bose-Einstein condensation (BEC) crossover theories above the transition temperature: Nozieres-Schmitt-Rink (NSR) theory and finite-T extended BCS-Leggett theory. The comparison is cast in the form of numerical studies of the behavior of the fermionic spectral function both theoretically and as constrained by (primarily) radio frequency (rf) experiments. Both theories include pair fluctuations and exhibit pseudogap effects, although the nature of this pseudogap is very different. The pseudogap in finite-T extended BCS-Leggett theory is found to follow a BCS-like dispersion which, in turn, is associated with a broadened BCS-like self-energy, rather more similar tomore » what is observed in high-temperature superconductors (albeit, for a d-wave case). The fermionic quasiparticle dispersion is different in NSR theory and the damping is considerably larger. We argue that the two theories are appropriate in different temperature regimes with the BCS-Leggett approach being more suitable nearer to condensation. There should, in effect, be little difference at higher T as the pseudogap becomes weaker and where the simplifying approximations used in the BCS-Leggett approach break down. On the basis of momentum-integrated rf studies of unpolarized gases, it would be difficult to distinguish which theory is the better one. A full comparison for polarized gases is not possible since it is claimed that there are inconsistencies in the NSR approach (not found in the BCS-Leggett scheme). Future experiments along the lines of momentum-resolved experiments look to be very promising in distinguishing the two theories.« less

'Candidatus Phytoplasma noviguineense', a novel taxon associated with Bogia coconut syndrome and banana wilt disease on the island of New Guinea.

PubMed

Miyazaki, Akio; Shigaki, Toshiro; Koinuma, Hiroaki; Iwabuchi, Nozomu; Rauka, Gou Bue; Kembu, Alfred; Saul, Josephine; Watanabe, Kiyoto; Nijo, Takamichi; Maejima, Kensaku; Yamaji, Yasuyuki; Namba, Shigetou

2018-01-01

Bogia coconut syndrome (BCS) is one of the lethal yellowing (LY)-type diseases associated with phytoplasma presence that are seriously threatening coconut cultivation worldwide. It has recently emerged, and is rapidly spreading in northern parts of the island of New Guinea. BCS-associated phytoplasmas collected in different regions were compared in terms of 16S rRNA gene sequences, revealing high identity among them represented by strain BCS-Bo R . Comparative analysis of the 16S rRNA gene sequences revealed that BCS-Bo R shared less than a 97.5 % similarity with other species of 'Candidatus Phytoplasma', with a maximum value of 96.08 % (with strain LY; GenBank accession no. U18747). This result indicates the necessity and propriety of a novel taxon for BCS phytoplasmas according to the recommendations of the IRPCM. Phylogenetic analysis was also conducted on 16S rRNA gene sequences, resulting in a monophyletic cluster composed of BCS-Bo R and other LY-associated phytoplasmas. Other phytoplasmas on the island of New Guinea associated with banana wilt and arecanut yellow leaf diseases showed high similarities to BCS-Bo R and were closely related to BCS phytoplasmas. Based on the uniqueness of their 16S rRNA gene sequences, a novel taxon 'Ca.Phytoplasma noviguineense' is proposed for these phytoplasmas found on the island of New Guinea, with strain BCS-Bo R (GenBank accession no. LC228755) as the reference strain. The novel taxon is described in detail, including information on the symptoms of associated diseases and additional genetic features of the secY gene and rp operon.

Gray's Ferry project: Phase II. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

A three-story rowhouse building was retrofitted to demonstrate solar heating and energy conservation in the Philadelphia, PA area. The retrofit included a solar greenhouse, a Trombe wall, and a solar hot water system. The Phase II Project funding was used for four specific endeavors: (1) tours; (2) brochures/literature; (3) a slide show presentation; and (4) signage showing the design of the active and passive solar systems. Three special workshops and more than fifteen tours of the building were given. A DOE funded study showed that a Trombe wall was the most cost-effective solar application for the 183,000 two-story brick rowmore » houses in the city. (BCS)« less

Induced interaction in a Fermi gas with a BEC-BCS crossover

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Zengqiang; Huang Kun; Yin Lan

2009-05-15

We study the effect of the induced interaction on the superfluid transition temperature of a Fermi gas with a Bose-Einstein condensation-Bardeen-Cooper-Schrieffer (BEC-BCS) crossover. The Gorkov-Melik-Barkhudarov theory about the induced interaction is extended from the BCS side to the entire crossover and the pairing fluctuation is treated in the approach by Nozieres and Schmitt-Rink. At unitarity, the induced interaction reduces the transition temperature by about 20%. In the BCS limit, the transition temperature is reduced by a factor of about 2.22, as found by Gorkov and Melik-Barkhudarov. Our result shows that the effect of the induced interaction is important both onmore » the BCS side and in the unitary region.« less

Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

PubMed

Kam, Julia W Y; Boyd, Lara A; Hsu, Chun L; Liu-Ambrose, Teresa; Handy, Todd C; Lim, Howard J; Hayden, Sherri; Campbell, Kristin L

2016-09-01

While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy.

Observing cellulose biosynthesis and membrane translocation in crystallo

PubMed Central

Morgan, Jacob L.W.; McNamara, Joshua T.; Fischer, Michael; Rich, Jamie; Chen, Hong-Ming; Withers, Stephen G.; Zimmer, Jochen

2016-01-01

Many biopolymers, including polysaccharides, must be translocated across at least one membrane to reach their site of biological function. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. In crystallo enzymology with the catalytically-active bacterial cellulose synthase BcsA-B complex reveals structural snapshots of a complete cellulose biosynthesis cycle, from substrate binding to polymer translocation. Substrate and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Furthermore, the structural snapshots show that BcsA translocates cellulose via a ratcheting mechanism involving a “finger helix” that contacts the polymer's terminal glucose. Cooperating with BcsA's gating loop, the finger helix moves ‘up’ and ‘down’ in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA’s transmembrane channel. This mechanism is validated experimentally by tethering BcsA's finger helix, which inhibits polymer translocation but not elongation. PMID:26958837

Ethnodrama: An Innovative Knowledge Translation Tool in the Management of Lymphedema.

PubMed

Ahmed, Shahid; Quinlan, Elizabeth; McMullen, Linda; Thomas, Roanne; Fichtner, Pam; Block, Janice

2015-01-01

Lymphedema can cause significant physical impairment and quality-of-life issues. Yet there is a gap in knowledge about lymphedema among breast cancer survivors (BCS), and health care professionals (HCP). Ethnodrama is an innovative knowledge translation strategy that uses theatrical performances for dissemination of research results. We evaluated the impact of live ethnodrama on HCP' and BCS' awareness and attitudes in relation to impact of lymphedema on BCS' lives. Ethnodrama performances were developed by script writers and a theatre director in collaboration with the investigators and BCS using data from published research and pre-performances workshops. Six interactive live performances were given to audiences of BCS, HCP, and community members in four cities across Canada. After watching these live performances, members of the audiences were asked to complete a paper-based questionnaire regarding their knowledge of lymphedema, and their attitudes and practices toward lymphedema. Of 238 audience members who participated in the survey, 55 (23%) were BCS and 85 (37.5%) were HCP. Most members rated the performances as very effective in changing their (84%) or other people's (93%) understanding of lymphedema; 96% reported being motivated to seek additional information on lymphedema, and 72% of HCP anticipated changes in their practices related to lymphedema screening. Overall no significant differences were noted in responses to ethnodrama between BCS and HCP. Open-ended responses were supportive of the findings from the closed-ended questions. Our results indicate that ethnodrama performances effectively convey information and positively affecting changes in HCP' and BCS' attitudes toward lymphedema.

Distinguishing between the Permeability Relationships with Absorption and Metabolism To Improve BCS and BDDCS Predictions in Early Drug Discovery

PubMed Central

2015-01-01

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug–drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption. PMID:24628254

Distinguishing between the permeability relationships with absorption and metabolism to improve BCS and BDDCS predictions in early drug discovery.

PubMed

Larregieu, Caroline A; Benet, Leslie Z

2014-04-07

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug-drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption.

Genetic correlations between body condition scores and fertility in dairy cattle using bivariate random regression models.

PubMed

De Haas, Y; Janss, L L G; Kadarmideen, H N

2007-10-01

Genetic correlations between body condition score (BCS) and fertility traits in dairy cattle were estimated using bivariate random regression models. BCS was recorded by the Swiss Holstein Association on 22,075 lactating heifers (primiparous cows) from 856 sires. Fertility data during first lactation were extracted for 40,736 cows. The fertility traits were days to first service (DFS), days between first and last insemination (DFLI), calving interval (CI), number of services per conception (NSPC) and conception rate to first insemination (CRFI). A bivariate model was used to estimate genetic correlations between BCS as a longitudinal trait by random regression components, and daughter's fertility at the sire level as a single lactation measurement. Heritability of BCS was 0.17, and heritabilities for fertility traits were low (0.01-0.08). Genetic correlations between BCS and fertility over the lactation varied from: -0.45 to -0.14 for DFS; -0.75 to 0.03 for DFLI; from -0.59 to -0.02 for CI; from -0.47 to 0.33 for NSPC and from 0.08 to 0.82 for CRFI. These results show (genetic) interactions between fat reserves and reproduction along the lactation trajectory of modern dairy cows, which can be useful in genetic selection as well as in management. Maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in mid lactation when the genetic variance for BCS is largest, and the genetic correlations between BCS and fertility is strongest.

Body condition score of Nellore beef cows: a heritable measure to improve the selection of reproductive and maternal traits.

PubMed

Fernandes, A F A; Neves, H H R; Carvalheiro, R; Oliveira, J A; Queiroz, S A

2015-08-01

Despite the economic importance of beef cattle production in Brazil, female reproductive performance, which is strongly associated with production efficiency, is not included in the selection index of most breeding programmes due to low heritability and difficulty in measure. The body condition score (BCS) could be used as an indicator of these traits. However, so far little is known about the feasibility of using BCS as a selection tool for reproductive performance in beef cattle. In this study, we investigated the sources of variation in the BCS of Nellore beef cows, quantified its association with reproductive and maternal traits and estimated its heritability. BCS was analysed using a logistic model that included the following effects: contemporary group at weaning, cow weight and hip height, calving order, reconception together with the weight and scores of conformation and early finishing assigned to calves at weaning. In the genetic analysis, variance components of BCS were estimated through Bayesian inference by fitting an animal model that also included the aforementioned effects. The results showed that BCS was significantly associated with all of the reproductive and maternal variables analysed. The estimated posterior mean of heritability of BCS was 0.24 (highest posterior density interval at 95%: 0.093 to 0.385), indicating an involvement of additive gene action in its determination. The present findings show that BCS can be used as a selection criterion for Nellore females.

Late Holocene earthquake history of the Brigham City segment of the Wasatch fault zone at the Hansen Canyon, Kotter Canyon, and Pearsons Canyon trench sites, Box Elder County, Utah

USGS Publications Warehouse

DuRoss, Christopher B.; Personius, Stephen F.; Crone, Anthony J.; McDonald, Greg N.; Briggs, Richard W.

2012-01-01

Of the five central segments of the Wasatch fault zone (WFZ) having evidence of recurrent Holocene surface-faulting earthquakes, the Brigham City segment (BCS) has the longest elapsed time since its most recent surface-faulting event (~2.1 kyr) compared to its mean recurrence time between events (~1.3 kyr). Thus, the BCS has the highest time-dependent earthquake probability of the central WFZ. We excavated trenches at three sites––the Kotter Canyon and Hansen Canyon sites on the north-central BCS and Pearsons Canyon site on the southern BCS––to determine whether a surface-faulting earthquake younger than 2.1 ka occurred on the BCS. Paleoseismic data for Hansen Canyon and Kotter Canyon confirm that the youngest earthquake on the north-central BCS occurred before 2 ka, consistent with previous north-central BCS investigations at Bowden Canyon and Box Elder Canyon. At Hansen Canyon, the most recent earthquake is constrained to 2.1–4.2 ka and had 0.6–2.5 m of vertical displacement. At Kotter Canyon, we found evidence for two events at 2.5 ± 0.3 ka and 3.5 ± 0.3 ka, with an average displacement per event of 1.9–2.3 m. Paleoseismic data from Pearsons Canyon, on the previously unstudied southern BCS, indicate that a post-2 ka earthquake ruptured this part of the segment. The Pearsons Canyon earthquake occurred at 1.2 ± 0.04 ka and had 0.1–0.8 m of vertical displacement, consistent with our observation of continuous, youthful scarps on the southern 9 km of the BCS having 1–2 m of late Holocene(?) surface offset. The 1.2-ka earthquake on the southern BCS likely represents rupture across the Weber–Brigham City segment boundary from the penultimate Weber-segment earthquake at about 1.1 ka. The Pearsons Canyon data result in a revised length of the BCS that has not ruptured since 2 ka (with time-dependent probability implications), and provide compelling evidence of at least one segment-boundary failure and multi-segment rupture on the central WFZ. Our paleoseismic investigations of the BCS clarify the timing, displacement, and extent of late Holocene earthquakes on the segment, and importantly, confirm the long elapsed time since the most recent earthquake on most of the BCS.

Overview of building energy use and report of analyses - 1985: buildings and community systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnader, M.; Lamontagne, J.

1985-10-01

The US Department of Energy (DOE) Office of Buildings and Community Systems (BCS) encourages increased efficiency of energy use in the buildings sector through the conduct of a comprehensive research program, the transfer of research results to industry, and the implementation of DOE's statutory responsibilities in the buildings area. This report summarizes the results of data development and analytical activities undertaken on behalf of BCS during 1985. It provides historical data on energy consumption patterns, prices, and building characteristics used in BCS's planning processes, documents BCS's detailed projections of energy use by end use and building type (the Disaggregate Projection),more » and compares this forecast to other forecasts. Summaries of selected recent BCS analyses are also provided.« less

Familial Budd-Chiari Syndrome in China: A Systematic Review of the Literature

PubMed Central

Qi, Xingshun; Wang, Juan; Ren, Weirong; Bai, Ming; Yang, Man; Han, Guohong; Fan, Daiming

2013-01-01

Familial occurrence of Budd-Chiari syndrome (BCS) has been reported in scattered cases, which potentially favors the congenital theory. A review of the literature was conducted to demonstrate this phenomenon in China. PubMed, VIP, and CNKI databases were searched for studies describing at least two Chinese BCS patients from the same one family. In the 18 eligible papers, 30 siblings or first-degree relatives from 14 families were diagnosed with BCS at 9 different centers. Common clinical presentations included varices of abdominal wall and lower limbs, edema of legs, and ascites. Type and location of obstruction were similar among these patients from the same one family. Screening for BCS was conducted in 65 family members from 3 families, demonstrating that 2 asymptomatic siblings from one family were further diagnosed with BCS. Factor V Leiden mutation was found in 3 of 4 patients from one family and in one of 2 patients from another one family. Prothrombin G20210A gene mutation was found in none of the 4 patients from the 2 families. In conclusion, our study showed the possibility of familial aggregation in Chinese BCS patients, but these available data cannot support the previous hypothesis that familial BCS originates from congenital vascular malformation. PMID:27335832

Behavioral and physiological effects of a short-term feed restriction in lactating dairy cattle with different body condition scores at calving.

PubMed

Schütz, K E; Cox, N R; Macdonald, K A; Roche, J R; Verkerk, G A; Rogers, A R; Tucker, C B; Matthews, L R; Meier, S; Webster, J R

2013-07-01

Body condition score (BCS) around calving, and the typical BCS loss for up to 100 d after parturition, is associated with both production and reproductive performance of dairy cattle. In addition, there is public concern that thin cows may have impaired welfare, particularly in early lactation where feed demand exceeds pasture growth, and a lag exists between peak milk energy requirements and intake. The aim of this experiment was to determine how BCS at calving influences behavioral and physiological responses to a short-term feed restriction at 47 DIM. Body condition score (on a 10-point scale) at calving was manipulated by modifying the diets in the previous lactation of healthy dairy cattle to generate 3 treatment groups: low BCS (3.4; n=17), medium BCS (4.6; n=18), or high BCS (5.4; n=20). Cows were tested in 4 groups for 8 consecutive days; testing consisted of different levels of feed allocation (d 1 and 2: 100%; d 3 and 4: 75%; d 5: 50%; d 6 to 8: 125%), where 100% was 15kg of DM/cow per day. All BCS groups had similar and marked behavioral and physiological responses to feed restriction. For example, they increased vocalization, time spent eating silage and grazing, aggressive behavior, and fat metabolism (as measured by concentrations of β-hydroxybutyrate and nonesterified fatty acids), and reduced milk production. Body condition affected some of these responses. Fewer cows with low BCS engaged in aggressive interactions in a feed competition test (trough filled with silage that could be consumed in 15 min) on the first day of feed restriction (low: 32%; medium: 74%; high: 64%; standard error of difference=15.4%). High BCS cows had greater concentrations of β-hydroxybutyrate and nonesterified fatty acids throughout the experimental period, which suggests more fat mobilization; however, plasma leptin and fecal glucocorticosteroid metabolite concentrations were unaffected by BCS. Whereas cows demonstrated marked responses to feed restriction, the results suggest that a BCS of 3.4, 4.6, or 5.4 in healthy cows at calving does not overwhelmingly influence this response at 47 DIM. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reduced Cortisol and Metabolic Responses of Thin Ewes to an Acute Cold Challenge in Mid-Pregnancy: Implications for Animal Physiology and Welfare

PubMed Central

Verbeek, Else; Oliver, Mark Hope; Waas, Joseph Rupert; McLeay, Lance Maxwell; Blache, Dominique; Matthews, Lindsay Ross

2012-01-01

Background Low food availability leading to reductions in Body Condition Score (BCS; 0 indicates emaciation and 5 obesity) in sheep often coincides with low temperatures associated with the onset of winter in New Zealand. The ability to adapt to reductions in environmental temperature may be impaired in animals with low BCS, in particular during pregnancy when metabolic demand is higher. Here we assess whether BCS affects a pregnant animal's ability to cope with cold challenges. Methods Eighteen pregnant ewes with a BCS of 2.7±0.1 were fed to attain low (LBC: BCS2.3±0.1), medium (MBC: BCS3.2±0.2) or high BCS (HBC: BCS3.6±0.2). Shorn ewes were exposed to a 6-h acute cold challenge in a climate-controlled room (wet and windy conditions, 4.4±0.1°C) in mid-pregnancy. Blood samples were collected during the BCS change phase, acute cold challenge and recovery phase. Results During the BCS change phase, plasma glucose and leptin concentrations declined while free fatty acids (FFA) increased in LBC compared to MBC (P<0.01, P<0.01 and P<0.05, respectively) and HBC ewes (P<0.05, P<0.01 and P<0.01, respectively). During the cold challenge, plasma cortisol concentrations were lower in LBC than MBC (P<0.05) and HBC ewes (P<0.05), and FFA and insulin concentrations were lower in LBC than HBC ewes (P<0.05 and P<0.001, respectively). Leptin concentrations declined in MBC and HBC ewes while remaining unchanged in LBC ewes (P<0.01). Glucose concentrations and internal body temperature (Tcore) increased in all treatments, although peak Tcore tended to be higher in HBC ewes (P<0.1). During the recovery phase, T4 concentrations were lower in LBC ewes (P<0.05). Conclusion Even though all ewes were able to increase Tcore and mobilize glucose, low BCS animals had considerably reduced cortisol and metabolic responses to a cold challenge in mid-pregnancy, suggesting that their ability to adapt to cold challenges through some of the expected pathways was reduced. PMID:22662144

Genetic relationships between body condition score and reproduction traits in Canadian Holstein and Ayrshire first-parity cows.

PubMed

Bastin, C; Loker, S; Gengler, N; Sewalem, A; Miglior, F

2010-05-01

The objective of this study was to investigate the genetic relationship between body condition score (BCS) and reproduction traits for first-parity Canadian Ayrshire and Holstein cows. Body condition scores were collected by field staff several times over the lactation in herds from Québec, and reproduction records (including both fertility and calving traits) were extracted from the official database used for the Canadian genetic evaluation of those herds. For each breed, six 2-trait animal models were run; they included random regressions that allowed the estimation of genetic correlations between BCS over the lactation and reproduction traits that are measured as a single lactation record. Analyses were undertaken on data from 108 Ayrshire herds and 342 Holstein herds. Average daily heritabilities of BCS were close to 0.13 for both breeds; these relatively low estimates might be explained by the high variability among herds and BCS evaluators. Genetic correlations between BCS and interval fertility traits (days from calving to first service, days from first service to conception, and days open) were negative and ranged between -0.77 and -0.58 for Ayrshire and between -0.31 and -0.03 for Holstein. Genetic correlations between BCS and 56-d nonreturn rate at first insemination were positive and moderate. The trends of these genetic correlations over the lactation suggest that a genetically low BCS in early lactation would increase the number of days that the primiparous cow was not pregnant and would decrease the chances of the primiparous cow to conceive at first service. Genetic correlations between BCS and calving traits were generally the strongest at calving and decreased with increasing days in milk. The correlation between BCS at calving and maternal calving ease was 0.21 for Holstein and 0.31 for Ayrshire and emphasized the relationship between fat cows around calving and dystocia. Genetic correlations between calving traits and BCS during the subsequent lactation were moderate and favorable, indicating that primiparous cows with a genetically high BCS over the lactation would have a greater chance of producing a calf that survived (maternal calf survival) and would transmit the genes that allowed the calf to be born more easily (maternal calving ease) and to survive (direct calving ease). Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Distinct Physiological Maturation of Parvalbumin-Positive Neuron Subtypes in Mouse Prefrontal Cortex.

PubMed

Miyamae, Takeaki; Chen, Kehui; Lewis, David A; Gonzalez-Burgos, Guillermo

2017-05-10

Parvalbumin-positive (PV + ) neurons control the timing of pyramidal cell output in cortical neuron networks. In the prefrontal cortex (PFC), PV + neuron activity is involved in cognitive function, suggesting that PV + neuron maturation is critical for cognitive development. The two major PV + neuron subtypes found in the PFC, chandelier cells (ChCs) and basket cells (BCs), are thought to play different roles in cortical circuits, but the trajectories of their physiological maturation have not been compared. Using two separate mouse lines, we found that in the mature PFC, both ChCs and BCs are abundant in superficial layer 2, but only BCs are present in deeper laminar locations. This distinctive laminar distribution was observed by postnatal day 12 (P12), when we first identified ChCs by the presence of axon cartridges. Electrophysiology analysis of excitatory synapse development, starting at P12, showed that excitatory drive remains low throughout development in ChCs, but increases rapidly before puberty in BCs, with an earlier time course in deeper-layer BCs. Consistent with a role of excitatory synaptic drive in the maturation of PV + neuron firing properties, the fast-spiking phenotype showed different maturation trajectories between ChCs and BCs, and between superficial versus deep-layer BCs. ChC and BC maturation was nearly completed, via different trajectories, before the onset of puberty. These findings suggest that ChC and BC maturation may contribute differentially to the emergence of cognitive function, primarily during prepubertal development. SIGNIFICANCE STATEMENT Parvalbumin-positive (PV + ) neurons tightly control pyramidal cell output. Thus PV + neuron maturation in the prefrontal cortex (PFC) is crucial for cognitive development. However, the relative physiological maturation of the two major subtypes of PV + neurons, chandelier cells (ChCs) and basket cells (BCs), has not been determined. We assessed the maturation of ChCs and BCs in different layers of the mouse PFC, and found that, from early postnatal age, ChCs and BCs differ in laminar location. Excitatory synapses and fast-spiking properties matured before the onset of puberty in both cell types, but following cell type-specific developmental trajectories. Hence, the physiological maturation of ChCs and BCs may contribute to the emergence of cognitive function differentially, and predominantly during prepubertal development. Copyright © 2017 the authors 0270-6474/17/374883-20$15.00/0.

Beliefs and attitudes about breast cancer and screening practices among Arab women living in Qatar: a cross-sectional study.

PubMed

Donnelly, Tam Truong; Al Khater, Al-Hareth; Al-Bader, Salha Bujassoum; Al Kuwari, Mohamed Ghaith; Al-Meer, Nabila; Malik, Mariam; Singh, Rajvir; Chaudhry, Sofia; Fung, Tak

2013-12-13

Despite rising breast cancer incidence and mortality rates, breast cancer screening (BCS) rates among women in Qatar remain low. Previous studies indicate the need to better understand the many complex beliefs, values, and attitudes that influence Arab women's health seeking behavior for the development of culturally appropriate and effective intervention strategies to address breast cancer in the Middle East. This study investigates beliefs, attitudes, and BCS practices of Arabic-speaking women in Qatar. A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) Arabic-speaking female Qatari citizens and non-Qatari residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Associations between beliefs and BCS practice were estimated using chi-square tests and multivariate logistic regression analyses. Participants who adhered to BCS guidelines (BCS practice = Yes) were compared to those who did not (BCS practice = No). In addition to low levels of awareness and low participation rates in BCS, one quarter of the participants stated their doctors talked to them about breast cancer, and less than half of the women interviewed believed breast cancer can be prevented. Women who engaged in BCS practice were more likely to have a doctor who talked to them about breast cancer, to believe they were in good-excellent health, that cancer can be prevented, or that cancer might be hereditary. The majority wanted to know if they had cancer and felt their health care needs were being met. The main reasons given for not planning BCS were lack of a doctor's recommendation, fear, and embarrassment. These findings indicate that a variety of channels (health care providers, media, breast cancer survivors, community leaders) should be utilized to create culturally appropriate breast cancer intervention programs and increased awareness of breast cancer, BCS, and the benefits of early detection of breast cancer. Employment of these measures will reduce breast cancer mortality rates among Arabic-speaking women living in the State of Qatar.

Beliefs and attitudes about breast cancer and screening practices among Arab women living in Qatar: a cross-sectional study

PubMed Central

2013-01-01

Background Despite rising breast cancer incidence and mortality rates, breast cancer screening (BCS) rates among women in Qatar remain low. Previous studies indicate the need to better understand the many complex beliefs, values, and attitudes that influence Arab women’s health seeking behavior for the development of culturally appropriate and effective intervention strategies to address breast cancer in the Middle East. This study investigates beliefs, attitudes, and BCS practices of Arabic-speaking women in Qatar. Methods A multicenter, cross-sectional quantitative survey of 1,063 (87.5% response rate) Arabic-speaking female Qatari citizens and non-Qatari residents, 35 years of age or older, was conducted in Qatar from March 2011 to July 2011. Associations between beliefs and BCS practice were estimated using chi-square tests and multivariate logistic regression analyses. Participants who adhered to BCS guidelines (BCS practice = Yes) were compared to those who did not (BCS practice = No). Results In addition to low levels of awareness and low participation rates in BCS, one quarter of the participants stated their doctors talked to them about breast cancer, and less than half of the women interviewed believed breast cancer can be prevented. Women who engaged in BCS practice were more likely to have a doctor who talked to them about breast cancer, to believe they were in good–excellent health, that cancer can be prevented, or that cancer might be hereditary. The majority wanted to know if they had cancer and felt their health care needs were being met. The main reasons given for not planning BCS were lack of a doctor’s recommendation, fear, and embarrassment. Conclusions These findings indicate that a variety of channels (health care providers, media, breast cancer survivors, community leaders) should be utilized to create culturally appropriate breast cancer intervention programs and increased awareness of breast cancer, BCS, and the benefits of early detection of breast cancer. Employment of these measures will reduce breast cancer mortality rates among Arabic-speaking women living in the State of Qatar. PMID:24330708

IMG-ABC. A knowledge base to fuel discovery of biosynthetic gene clusters and novel secondary metabolites

DOE PAGES

Hadjithomas, Michalis; Chen, I-Min Amy; Chu, Ken; ...

2015-07-14

In the discovery of secondary metabolites, analysis of sequence data is a promising exploration path that remains largely underutilized due to the lack of computational platforms that enable such a systematic approach on a large scale. In this work, we present IMG-ABC (https://img.jgi.doe.gov/abc), an atlas of biosynthetic gene clusters within the Integrated Microbial Genomes (IMG) system, which is aimed at harnessing the power of “big” genomic data for discovering small molecules. IMG-ABC relies on IMG’s comprehensive integrated structural and functional genomic data for the analysis of biosynthetic gene clusters (BCs) and associated secondary metabolites (SMs). SMs and BCs serve asmore » the two main classes of objects in IMG-ABC, each with a rich collection of attributes. A unique feature of IMG-ABC is the incorporation of both experimentally validated and computationally predicted BCs in genomes as well as metagenomes, thus identifying BCs in uncultured populations and rare taxa. We demonstrate the strength of IMG-ABC’s focused integrated analysis tools in enabling the exploration of microbial secondary metabolism on a global scale, through the discovery of phenazine-producing clusters for the first time in lphaproteobacteria. IMG-ABC strives to fill the long-existent void of resources for computational exploration of the secondary metabolism universe; its underlying scalable framework enables traversal of uncovered phylogenetic and chemical structure space, serving as a doorway to a new era in the discovery of novel molecules. IMG-ABC is the largest publicly available database of predicted and experimental biosynthetic gene clusters and the secondary metabolites they produce. The system also includes powerful search and analysis tools that are integrated with IMG’s extensive genomic/metagenomic data and analysis tool kits. As new research on biosynthetic gene clusters and secondary metabolites is published and more genomes are sequenced, IMG-ABC will continue to expand, with the goal of becoming an essential component of any bioinformatic exploration of the secondary metabolism world.« less

Ethnodrama: An Innovative Knowledge Translation Tool in the Management of Lymphedema

PubMed Central

Ahmed, Shahid; Quinlan, Elizabeth; McMullen, Linda; Thomas, Roanne; Fichtner, Pam; Block, Janice

2015-01-01

Background: Lymphedema can cause significant physical impairment and quality-of-life issues. Yet there is a gap in knowledge about lymphedema among breast cancer survivors (BCS), and health care professionals (HCP). Ethnodrama is an innovative knowledge translation strategy that uses theatrical performances for dissemination of research results. We evaluated the impact of live ethnodrama on HCP' and BCS' awareness and attitudes in relation to impact of lymphedema on BCS' lives. Methods: Ethnodrama performances were developed by script writers and a theatre director in collaboration with the investigators and BCS using data from published research and pre-performances workshops. Six interactive live performances were given to audiences of BCS, HCP, and community members in four cities across Canada. After watching these live performances, members of the audiences were asked to complete a paper-based questionnaire regarding their knowledge of lymphedema, and their attitudes and practices toward lymphedema. Results: Of 238 audience members who participated in the survey, 55 (23%) were BCS and 85 (37.5%) were HCP. Most members rated the performances as very effective in changing their (84%) or other people's (93%) understanding of lymphedema; 96% reported being motivated to seek additional information on lymphedema, and 72% of HCP anticipated changes in their practices related to lymphedema screening. Overall no significant differences were noted in responses to ethnodrama between BCS and HCP. Open-ended responses were supportive of the findings from the closed-ended questions. Conclusions: Our results indicate that ethnodrama performances effectively convey information and positively affecting changes in HCP' and BCS' attitudes toward lymphedema. PMID:26284137

Primary Budd-Chiari syndrome - a single center experience.

PubMed

Raszeja-Wyszomirska, Joanna; Mieżyńska-Kurtycz, Joanna; Marlicz, Wojciech; Lawniczak, Małgorzata; Wójcicki, Maciej

2012-09-01

Budd-Chiari syndrome (BCS) is recognized as a clinical manifestation of various prothrombotic conditions which may be lethal within 3 years of the onset of symptoms if untreated. This study is a retrospective analysis of patients with BCS managed between 2004 and 2011. The diagnosis was confirmed with contrast CT-angiography and/or Doppler ultrasound. BCS was diagnosed in 20 patients (11 females and 9 males), median age 38 years (ranging from 18 to 56). Twelve patients were referred as acute BCS for the liver transplant (LTx) assessment. Thrombosis of the hepatic veins was caused by myeloproliferative disorders (n=8), end-stage liver disease (n=4), protein C deficiency (n=3), paroxysmal nocturnal hemoglobinuria (PNH) (n=1), antiphospholipid syndrome (n=1) and secondary poliglobulia (n=1). In two patients the origin of BCS could not be established despite appropriate screening. Median follow-up was 29 months. Low molecular heparin with subsequent conversion to vitamin K antagonists was routinely applied in all patients. Two patients underwent TIPS procedure with good long term outcome and 10 subjects received LTx; 1 patient was lost to follow-up and 1 died of chest infection 9 years since the diagnosis of BCS was made; 14 patients, including those who received LTx, were alive and well at least one year after BCS diagnosis. All survivors remain stable and are followed-up on a regular basis. Strict adherence to the diagnostic and therapeutic guidelines plays a crucial role in the management of BCS patients. Our results confirm the efficacy of anticoagulation as well as TIPS and/or OLT in treatment of this rare condition.

Assessment of Body Condition in African (Loxodonta africana) and Asian (Elephas maximus) Elephants in North American Zoos and Management Practices Associated with High Body Condition Scores.

PubMed

Morfeld, Kari A; Meehan, Cheryl L; Hogan, Jennifer N; Brown, Janine L

2016-01-01

Obesity has a negative effect on health and welfare of many species, and has been speculated to be a problem for zoo elephants. To address this concern, we assessed the body condition of 240 elephants housed in North American zoos based on a set of standardized photographs using a 5-point Body Condition Score index (1 = thinnest; 5 = fattest). A multi-variable regression analysis was then used to determine how demographic, management, housing, and social factors were associated with an elevated body condition score in 132 African (Loxodonta africana) and 108 Asian (Elephas maximus) elephants. The highest BCS of 5, suggestive of obesity, was observed in 34% of zoo elephants. In both species, the majority of elephants had elevated BCS, with 74% in the BCS 4 (40%) and 5 (34%) categories. Only 22% of elephants had BCS 3, and less than 5% of the population was assigned the lowest BCS categories (BCS 1 and 2). The strongest multi-variable model demonstrated that staff-directed walking exercise of 14 hours or more per week and highly unpredictable feeding schedules were associated with decreased risk of BCS 4 or 5, while increased diversity in feeding methods and being female was associated with increased risk of BCS 4 or 5. Our data suggest that high body condition is prevalent among North American zoo elephants, and management strategies that help prevent and mitigate obesity may lead to improvements in welfare of zoo elephants.

Assessment of Body Condition in African (Loxodonta africana) and Asian (Elephas maximus) Elephants in North American Zoos and Management Practices Associated with High Body Condition Scores

PubMed Central

Morfeld, Kari A.; Meehan, Cheryl L.; Hogan, Jennifer N.; Brown, Janine L.

2016-01-01

Obesity has a negative effect on health and welfare of many species, and has been speculated to be a problem for zoo elephants. To address this concern, we assessed the body condition of 240 elephants housed in North American zoos based on a set of standardized photographs using a 5-point Body Condition Score index (1 = thinnest; 5 = fattest). A multi-variable regression analysis was then used to determine how demographic, management, housing, and social factors were associated with an elevated body condition score in 132 African (Loxodonta africana) and 108 Asian (Elephas maximus) elephants. The highest BCS of 5, suggestive of obesity, was observed in 34% of zoo elephants. In both species, the majority of elephants had elevated BCS, with 74% in the BCS 4 (40%) and 5 (34%) categories. Only 22% of elephants had BCS 3, and less than 5% of the population was assigned the lowest BCS categories (BCS 1 and 2). The strongest multi-variable model demonstrated that staff-directed walking exercise of 14 hours or more per week and highly unpredictable feeding schedules were associated with decreased risk of BCS 4 or 5, while increased diversity in feeding methods and being female was associated with increased risk of BCS 4 or 5. Our data suggest that high body condition is prevalent among North American zoo elephants, and management strategies that help prevent and mitigate obesity may lead to improvements in welfare of zoo elephants. PMID:27415629

Pairing fluctuations and the superfluid density through the BCS-BEC crossover

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, E.; Griffin, A.; Fukushima, N.

2006-12-15

We derive an expression for the superfluid density of a uniform two-component Fermi gas through the BCS-BEC crossover in terms of the thermodynamic potential in the presence of an imposed superfluid flow. Treating the pairing fluctuations in a Gaussian approximation following the approach of Nozieres and Schmitt-Rink, we use this definition of {rho}{sub s} to obtain an explicit result which is valid at finite temperatures and over the full BCS-BEC crossover. It is crucial that the BCS gap {delta}, the chemical potential {mu}, and {rho}{sub s} all include the effect of fluctuations at the same level in a self-consistent manner.more » We show that the normal fluid density {rho}{sub n}{identical_to}n-{rho}{sub s} naturally separates into a sum of contributions from Fermi BCS quasiparticles ({rho}{sub n}{sup F}) and Bose collective modes ({rho}{sub n}{sup B}). The expression for {rho}{sub n}{sup F} is just Landau's formula for a BCS Fermi superfluid but now calculated over the BCS-BEC crossover. The expression for the Bose contribution {rho}{sub n}{sup B} is more complicated and only reduces to Landau's formula for a Bose superfluid in the extreme BEC limit, where all the fermions have formed stable Bose pairs and the Bogoliubov excitations of the associated molecular Bose condensate are undamped. In a companion paper, we present numerical calculations of {rho}{sub s} using an expression equivalent to the one derived in this paper, over the BCS-BEC crossover, including unitarity, and at finite temperatures.« less

Effect of nutritional status on the ovarian follicular population, yield and quality of oocytes in the Ngaoundere Gudali zebu (Bos indicus)

PubMed Central

Kouamo, Justin; Tidjou, Sorelle Gwladys Djatche; Zoli, Andre Pagnah; Mfopit, Youssouf Mouliom

2015-01-01

Aim: The aim of this study was to investigate the effect of nutritional status of the Gudali cows slaughtered at the Ngaoundere abattoir on follicular population, quality, and oocytes yield. Materials and Methods: Blood and ovaries were collected from 81 cows aged 6.35±0.24 years (3-12 years old), with a body condition score (BCS) of 2.93±0.09 (1-5). In each ovary, the follicle were counted and classified as small (<3 mm), medium (3-8 mm) and large (>8 mm) using an electronic caliper. Oocytes were collected by slicing technique and classified according to the homogeneity of the cytoplasm and layers of granulosa into four groups: I, II, III, and IV. The nutritional status of the animals was determined by quantification of serum glucose, total cholesterol, total protein, albumin, globulins, urea, and phosphorus level. Results: Of the total 162 ovaries harvested, 2916 follicles were counted on the ovarian surface with an average population of 36.00±2.17 follicles/cow. According to a size distribution, 16.67±1.54 (46.3%), 18.83±1.27 (52.3%), and 0.51±0.07 (1.4%), respectively for small (<3 mm), medium (3-8 mm), and large (>8 mm) were recorded. About 1,929 oocytes were obtained, with an average recovered of 23.81±1.53 oocytes/cow. Depending on the quality, 7.79±0.55 (32.7%), 6.04±0.41 (25.3%), 4.89±0.44 (20.6%), and 5.10±0.54 (21.4%) oocytes qualities I, II, III, and IV were obtained respectively; with an average cultivable oocyte recovered of 13.83±0.89 (58%). Cows with BCS > 3 and a high albumin and phosphorus level showed a highest number of follicles and oocytes able for in vitro maturation. Conclusion: These results indicated that nutrition remains an important factor for the in vitro production of the good embryo and the BCS is a useful tool for the selection of females’ oocytes donors. PMID:27047123

Evaluation of a model to improve collection of blood cultures in patients with sepsis in the emergency room.

PubMed

Mariani, B; Corbella, M; Seminari, E; Sacco, L; Cambieri, P; Capra Marzani, F; Martino, I F; Bressan, M A; Muzzi, A; Marena, C; Tinelli, C; Marone, P

2018-02-01

Sepsis begins outside of the hospital for nearly 80% of patients and the emergency room (ER) represents the first contact with the health care system. This study evaluates a project to improve collection of blood cultures (BCs) in patients with sepsis in the ER consisting of staff education and completion of the appropriate BC pre-analytical phase. A retrospective observational study performed to analyse the data on BC collection in the ER before and after a three-phase project. The first phase (1 January to 30 June 2015) before the intervention consisted of evaluation of data on BCs routinely collected in the ER. The second phase (1 July to 31 December 2015) was the intervention phase in which educational courses on sepsis recognition and on pre-analytical phase procedures (including direct incubation) were provided to ER staff. The third phase (1 January to 30 June 2016; after the intervention) again consisted of evaluation. Before the intervention, out of 24,738 admissions to the ER, 103 patients (0.4%) were identified as septic and had BCs drawn (359 BC bottles); 19 out of 103 patients (18.4%) had positive BCs. After the intervention, out of 24,702 admissions, 313 patients (1.3%) had BCs drawn (1,242 bottles); of these, 96 (30.7%) had positive BCs. Comparing the first and third periods, an increase in the percentage of patients with BCs collected (from 0.4% to 1.3% respectively, p < 0.0001) and an increase in the percentages of patients with true-positive BCs (from 0.08% to 0.39% of all patients evaluated respectively, p < 0.0001) were observed. The isolation of bacteria by BCs increased 3.25-fold after project implementation. These results can be principally ascribed to an improved awareness of sepsis in the staff associated with improved pre-analytical phase procedures in BC collection.

Relationships between fertility and postpartum changes in body condition and body weight in lactating dairy cows

PubMed Central

Carvalho, P. D.; Souza, A. H.; Amundson, M. C.; Hackbart, K. S.; Fuenzalida, M. J.; Herlihy, M. M.; Ayres, H.; Dresch, A. R.; Vieira, L. M.; Guenther, J. N.; Grummer, R. R.; Fricke, P. M.; Shaver, R. D.; Wiltbank, M. C.

2018-01-01

The relationship between energy status and fertility in dairy cattle was retrospectively analyzed by comparing fertility with body condition score (BCS) near artificial insemination (AI; experiment 1), early postpartum changes in BCS (experiment 2), and postpartum changes in body weight (BW; experiment 3). To reduce the effect of cyclicity status, all cows were synchronized with Double-Ovsynch protocol before timed AI. In experiment 1, BCS of lactating dairy cows (n = 1,103) was evaluated near AI. Most cows (93%) were cycling at initiation of the breeding Ovsynch protocol (first GnRH injection). A lower percentage pregnant to AI (P/AI) was found in cows with lower (≤2.50) versus higher (≥2.75) BCS (40.4 vs. 49.2%). In experiment 2, lactating dairy cows on 2 commercial dairies (n = 1,887) were divided by BCS change from calving until the third week postpartum. Overall, P/AI at 70-d pregnancy diagnosis differed dramatically by BCS change and was least for cows that lost BCS, intermediate for cows that maintained BCS, and greatest for cows that gained BCS [22.8% (180/789), 36.0% (243/675), and 78.3% (331/423), respectively]. Surprisingly, a difference existed between farms with BCS change dramatically affecting P/AI on one farm and no effect on the other farm. In experiment 3, lactating dairy cows (n = 71) had BW measured weekly from the first to ninth week postpartum and then had superovulation induced using a modified Double-Ovsynch protocol. Cows were divided into quartiles (Q) by percentage of BW change (Q1 = least change; Q4 = most change) from calving until the third week postpartum. No effect was detected of quartile on number of ovulations, total embryos collected, or percentage of oocytes that were fertilized; however, the percentage of fertilized oocytes that were transferable embryos was greater for cows in Q1, Q2, and Q3 than Q4 (83.8, 75.2, 82.6, and 53.2%, respectively). In addition, percentage of degenerated embryos was least for cows in Q1, Q2, and Q3 and greatest for Q4 (9.6, 14.5, 12.6, and 35.2% respectively). In conclusion, for cows synchronized with a Double-Ovsynch protocol, an effect of low BCS (≤2.50) near AI on fertility was detected, but change in BCS during the first 3 wk postpartum had a more profound effect on P/AI to first timed AI. This effect could be partially explained by the reduction in embryo quality and increase in degenerate embryos by d 7 after AI in cows that lost more BW from the first to third week postpartum. PMID:24731646

Relationships between fertility and postpartum changes in body condition and body weight in lactating dairy cows.

PubMed

Carvalho, P D; Souza, A H; Amundson, M C; Hackbart, K S; Fuenzalida, M J; Herlihy, M M; Ayres, H; Dresch, A R; Vieira, L M; Guenther, J N; Grummer, R R; Fricke, P M; Shaver, R D; Wiltbank, M C

2014-01-01

The relationship between energy status and fertility in dairy cattle was retrospectively analyzed by comparing fertility with body condition score (BCS) near artificial insemination (AI; experiment 1), early postpartum changes in BCS (experiment 2), and postpartum changes in body weight (BW; experiment 3). To reduce the effect of cyclicity status, all cows were synchronized with Double-Ovsynch protocol before timed AI. In experiment 1, BCS of lactating dairy cows (n = 1,103) was evaluated near AI. Most cows (93%) were cycling at initiation of the breeding Ovsynch protocol (first GnRH injection). A lower percentage pregnant to AI (P/AI) was found in cows with lower (≤ 2.50) versus higher (≥ 2.75) BCS (40.4 vs. 49.2%). In experiment 2, lactating dairy cows on 2 commercial dairies (n = 1,887) were divided by BCS change from calving until the third week postpartum. Overall, P/AI at 70-d pregnancy diagnosis differed dramatically by BCS change and was least for cows that lost BCS, intermediate for cows that maintained BCS, and greatest for cows that gained BCS [22.8% (180/789), 36.0% (243/675), and 78.3% (331/423), respectively]. Surprisingly, a difference existed between farms with BCS change dramatically affecting P/AI on one farm and no effect on the other farm. In experiment 3, lactating dairy cows (n = 71) had BW measured weekly from the first to ninth week postpartum and then had superovulation induced using a modified Double-Ovsynch protocol. Cows were divided into quartiles (Q) by percentage of BW change (Q1 = least change; Q4 = most change) from calving until the third week postpartum. No effect was detected of quartile on number of ovulations, total embryos collected, or percentage of oocytes that were fertilized; however, the percentage of fertilized oocytes that were transferable embryos was greater for cows in Q1, Q2, and Q3 than Q4 (83.8, 75.2, 82.6, and 53.2%, respectively). In addition, percentage of degenerated embryos was least for cows in Q1, Q2, and Q3 and greatest for Q4 (9.6, 14.5, 12.6, and 35.2% respectively). In conclusion, for cows synchronized with a Double-Ovsynch protocol, an effect of low BCS (≤ 2.50) near AI on fertility was detected, but change in BCS during the first 3 wk postpartum had a more profound effect on P/AI to first timed AI. This effect could be partially explained by the reduction in embryo quality and increase in degenerate embryos byd 7 after AI in cows that lost more BW from the first to third week postpartum. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Thermal transitions, pseudogap behavior, and BCS-BEC crossover in Fermi-Fermi mixtures

NASA Astrophysics Data System (ADS)

Karmakar, Madhuparna

2018-03-01

We study the mass imbalanced Fermi-Fermi mixture within the framework of a two-dimensional lattice fermion model. Based on the thermodynamic and species-dependent quasiparticle behavior, we map out the finite-temperature phase diagram of this system and show that unlike the balanced Fermi superfluid, there are now two different pseudogap regimes as PG-I and PG-II. While within the PG-I regime both the fermionic species are pseudogapped, PG-II corresponds to the regime where pseudogap feature survives only in the light species. We believe that the single-particle spectral features that we discuss in this paper are observable through the species-resolved radio-frequency spectroscopy and momentum-resolved photoemission spectroscopy measurements on systems such as 6Li-40K mixture. We further investigate the interplay between the population and mass imbalances and report that at a fixed population imbalance, the BCS-BEC crossover in a Fermi-Fermi mixture would require a critical interaction (Uc) for the realization of the uniform superfluid state. The effect of imbalance in mass on the exotic Fulde-Ferrell-Larkin-Ovchinnikov superfluid phase has been probed in detail in terms of the thermodynamic and quasiparticle behavior of this phase. It has been observed that in spite of the s -wave symmetry of the pairing field, a nodal superfluid gap is realized in the Larkin-Ovchinnikov regime. Our results on the various thermal scales and regimes are expected to serve as benchmarks for the experimental observations on 6Li-40K mixture.

Nano-sized water-in-oil-in-water emulsion enhances intestinal absorption of calcein, a high solubility and low permeability compound.

PubMed

Koga, Kenjiro; Takarada, Nobuo; Takada, Kanji

2010-02-01

Our goal was to develop safe and stable multilayer emulsions capable of enhancing intestinal absorption of biopharmaceutics classification system (BCS) class III drugs. First, w/o emulsions were prepared using calcein as a model BCS class III compound and condensed ricinoleic acid tetraglycerin ester as a hydrophobic emulsifier. Then water-in-oil-in-water (w/o/w) emulsions were prepared with shirasu porous glass (SPG) membranes. Particle size analyses and calcein leakage from oil droplets in w/o/w emulsions led us to select stearic acid hexaglycerin esters (HS-11) and Gelucire 44/14 as hydrophilic emulsifiers. Analyses of the absorption-enhancing effects of w/o/w emulsions on intestinal calcein absorption in rats showed that calcein bioavailability after intraduodenal (i.d.) administration of HS-11 or Gelucire 44/14+polyvinyl alcohol (PVA) w/o/w emulsions prepared with 0.1-microm pore-sized SPGs was significantly higher than that of the calcein control. However, serum calcein concentration vs. time profiles after i.d. administration of w/o/w emulsions prepared with 1.1-microm and 30-microm pore-sized SPGs and an emulsion prepared with a calcein-containing outer water phase were comparable to control profiles. These results suggested that HS-11 or Gelucire 44/14+PVA are safe outer water phase additives and that 0.1-microm pore-sized SPGs are important for preparing w/o/w emulsions that enhanced intestinal calcein absorption. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Stent Angioplasty of Closed Mesocaval Shunt in a Patient with Budd-Chiari Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sancak, Tanzer; Karagulle, Ayse Tuba; Bilgic, Sadik

Budd-Chiari syndrome (BCS) is an uncommon disorder caused by hepatic venous outflow obstruction. It is characterized by ascites, hepatomegaly and abdominal pain. Percutaneous intervention shave recently been used for the treatment of BCS. We present a case of BCS with a closed mesocaval shunt which was reopened with a self-expandable metallic stent.

Association of Breast Conservation Surgery for Cancer With 90-Day Reoperation Rates in New York State.

PubMed

Isaacs, Abby J; Gemignani, Mary L; Pusic, Andrea; Sedrakyan, Art

2016-07-01

For early-stage breast cancer, breast conservation surgery (BCS) is a conservative option for women and involves removing the tumor with a margin of surrounding breast tissue. If margins are not tumor free, patients undergo additional surgery to avoid local recurrence. To investigate the use of BCS in New York State and to determine rates of reoperation, procedure choice, and the effect of surgeon experience on the odds of a reoperation 90 days after BCS. A population-based sample of 89 448 women undergoing primary BCS for cancer were selected and examined from January 1, 2003, to December 31, 2013, in New York State mandatory reporting databases. All hospitals and ambulatory surgery centers in New York State were included. Data were analyzed from December 15, 2014, to November 1, 2015. Rate of reoperations within 90 days of the initial BCS procedure. During the study period, 89 448 women 20 years or older (mean [SD] age, 61.7 [13.7] years) underwent primary BCS. In 2013, 1416 women in New York aged 20 to 49 years underwent BCS compared with 3068 women aged 50 to 64 years and 3644 women 65 years or older. These numbers represent a significant decrease from 1960 women younger than 50 years in 2003 who underwent BCS (P < .001 for trend) but little change from the 2899 women aged 50 to 64 years and 3270 women 65 years or older who underwent BCS in 2003. Mean overall rate of 90-day reoperation was 30.9% (27 010 of 87 499 patients) and decreased over time from 39.5% (6630 of 16 805 patients) in 2003 to 2004 to 23.1% (5148 of 22 286 patients) in 2011 to 2013. Rates of reoperation were highest in women aged 20 to 49 years (37.7% [6990 of 18 524]) and lowest in women 65 years or older (26.3% [9656 of 36 691]) (P < .001 for trend). Over time, more patients underwent BCS as a subsequent procedure, from 4237 of 6630 patients (63.9%) in 2003 to 2004 to 4258 of 5148 (82.7%) in 2011 to 2013 (P < .001 for trend). Among the 19 466 women who underwent BCS as a second procedure, 2429 (12.5%) required a third intervention (2.7% of all women included). Significant surgeon-level variation was found in the data; 90-day rates of reoperations by surgeon ranged from 0% to 100%. Low-volume surgeons (<14 cases per year) had an unadjusted rate of 35.2% compared with 29.6% in middle-volume (14-33 cases per year) and 27.5% in high-volume (≥34 cases per year) surgeons. The difference persisted in adjusted analyses (odds ratio for low-volume surgeons, 1.49 [95% CI, 1.19-1.87]; for middle-volume surgeons, 1.20 [95% CI, 0.93-1.56]) compared with high-volume surgeons (used as the reference category). Use of BCS has decreased overall, most steeply in younger women. Nearly 1 in 4 women underwent a reoperation within 90 days of BCS across New York State from 2011 to 2013, compared with 2 in 5 from 2003 to 2004. Rates vary significantly by surgeon, and initial BCS performed by high-volume surgeons was associated with a 33% lower risk for a reoperation.

Development of stability-enhanced ternary solid dispersions via combinations of HPMCP and Soluplus® processed by hot melt extrusion.

PubMed

Albadarin, Ahmad B; Potter, Catherine B; Davis, Mark T; Iqbal, Javed; Korde, Sachin; Pagire, Sudhir; Paradkar, Anant; Walker, Gavin

2017-10-30

The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus ® polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug. The ASDs were characterized by Powder X-Ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Solid State Nuclear Magnetic Resonance (ssNMR) and dissolution studies. The data showed that the ASDs were physically and chemically stable at 20°C and 50% RH over 12 months. PXRD results indicated that the ITZ in the ASDs was in the amorphous state and no recrystallization occurred. DSC scans confirmed that each formulation exhibited a single intermediate glass transition (T g ), around 96.4°C, indicating that ITZ was completely miscible in the polymeric blends of HPMCP and Soluplus ® at up to 30% (w/w) drug loading and that the two polymers were miscible with each other in the presence of ITZ. The FTIR analysis indicated the formation of strong hydrogen bonding between ITZ, HPMCP and Soluplus ® . The dissolution end-point of the ASDs was determined to be approximately 10 times greater than that of the crystalline ITZ. Copyright © 2017 Elsevier B.V. All rights reserved.

An update on the management of Budd-Chiari syndrome: the issues of timing and choice of treatment.

PubMed

Mancuso, Andrea

2015-03-01

Because of the rarity of Budd-Chiari syndrome (BCS), the flow chart of management comes from expert opinion and is not evidence based. To report an update on the management of BCS. I performed a review on published papers on BCS in an attempt to speculate in particular on the timing and the choice of treatment. Some authors suggest that the management of BCS should follow a step-wise strategy. Anticoagulation and medical therapy should be the first-line treatment. Revascularization or transjugular intrahepatic portosystemic shunt should be performed in case of no response to medical therapy. Orthotopic liver transplant should be used as a rescue therapy. The biggest criticism of this flow chart is that it is based on the assumption that patients with BCS should receive further treatment only when hemodynamic effects on portal hypertension become clinically evident, thus paying little attention to the chronic ischemic liver damage effects on hepatic function and to the possibility of preventing liver failure by relieving impaired hepatic veins outflow. Recently, I presented a proposal of a new algorithm for the management of BCS, in which medical therapy alone is suggested only for patients without any sign of portal hypertension, irrespective of whether early interventional treatment is suggested when either any symptoms or signs of portal hypertension appear, with the aim of preventing hepatic fibrosis development, disease progression, and finally improving outcome. Given that the benefit of treatments for BCS is not under debate, guidelines for the management of BCS should be re-evaluated and updated, with particular attention to both the timing and the choice of treatment.

Short communication: effects of serum obtained from dairy cows with low or high body condition score on in vitro embryo development.

PubMed

Oba, M; Miyashita, S; Nishii, R; Koiwa, M; Koyama, H; Ambrose, D J; Dochi, O

2013-03-01

The objective of the study was to determine whether the serum obtained from animals differing in body condition score (BCS) affects in vitro embryo development. After in vitro fertilization, serum obtained from dairy cows of either low (L-BCS; 2.1 ± 0.14 on a scale of 1 to 5) or high BCS (H-BCS; 4.0 ± 0.0), or commercially available bovine serum (control) was added at 5% concentration to the in vitro culture medium. Use of serum obtained from H-BCS cows increased the cleavage rates compared with control serum at both 24 and 48 h after in vitro fertilization (78.3 vs. 71.9% and 79.9 vs. 75.1%, respectively), whereas use of serum obtained from L-BCS cows increased the blastocyst rate compared with control serum at 7d (23.8 vs. 19.1%), but this difference was not evident at 8 or 9 d after in vitro fertilization. As nonesterified fatty acid concentrations were highest in control serum, followed by serum from L-BCS and H-BCS cows (621, 559, and 272 μEq/L, respectively), a high concentration of nonesterified fatty acids might adversely affect the very early stages of embryo development, and its negative effects might be greater immediately after fertilization compared with developmental stages after morula formation. Our findings also indicate that factors promoting early stage embryo development do not necessarily promote blastocyst development. Serum obtained from animals under different physiological conditions may be used for in vitro embryo culture to study the effects of nutritional management of dairy cattle on embryo development. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Adsorption of β-casein-surfactant mixed layers at the air-water interface evaluated by interfacial rheology.

PubMed

Maestro, Armando; Kotsmar, Csaba; Javadi, Aliyar; Miller, Reinhard; Ortega, Francisco; Rubio, Ramón G

2012-04-26

This work presents a detailed study of the dilational viscoelastic moduli of the adsorption layers of the milk protein β-casein (BCS) and a surfactant at the liquid/air interface, over a broad frequency range. Two complementary techniques have been used: a drop profile tensiometry technique and an excited capillary wave method, ECW. Two different surfactants were studied: the nonionic dodecyldimethylphosphine oxide (C12DMPO) and the cationic dodecyltrimethylammonium bromide (DoTAB). The interfacial dilational elasticity and viscosity are very sensitive to the composition of protein-surfactant mixed adsorption layers at the air/water interface. Two different dynamic processes have been observed for the two systems studied, whose characteristic frequencies are close to 0.01 and 100 Hz. In both systems, the surface elasticity was found to show a maximum when plotted versus the surfactant concentration. However, at frequencies above 50 Hz the surface elasticity of BCS + C12DMPO is higher than the one of the aqueous BCS solution over most of the surfactant concentration range, whereas for the BCS + DoTAB it is smaller for high surfactant concentrations and higher at low concentrations. The BCS-surfactant interaction modifies the BCS random coil structure via electrostatic and/or hydrophobic interactions, leading to a competitive adsorption of the BCS-surfactant complexes with the free, unbound surfactant molecules. Increasing the surfactant concentration decreases the adsorbed proteins. However, the BCS molecules are rather strongly bound to the interface due to their large adsorption energy. The results have been fitted to the model proposed by C. Kotsmar et al. ( J. Phys. Chem. B 2009 , 113 , 103 ). Even though the model describes well the concentration dependence of the limiting elasticity, it does not properly describe its frequency dependence.

Patterns of initial management of node-negative breast cancer in two Canadian provinces

PubMed Central

Goel, V; Olivotto, I; Hislop, T G; Sawka, C; Coldman, A; Holowaty, E J

1997-01-01

OBJECTIVE: To describe the patterns of initial management of node-negative breast cancer in Ontario and British Columbia and to compare the characteristics of the patients and tumours and of the physicians and hospitals involved in management. DESIGN: Retrospective, population-based, cohort study. PARTICIPANTS: All 942 newly diagnosed cases of node-negative breast cancer in 1991 in British Columbia and a random sample of 938 newly diagnosed cases in Ontario in the same year. OUTCOME MEASURES: Number and proportion of patients with newly diagnosed node-negative breast cancer who received breast-conserving surgery (BCS) or mastectomy and who received radiation therapy after BCS. RESULTS: BCS was used in 413 cases (43.8%) in British Columbia and in 634 cases (67.6%) in Ontario (p < 0.001). After BCS, radiation therapy was received by 378 patients (91.5% of those who had undergone BCS) in British Columbia and 479 patients (75.6% of those who had undergone BCS) in Ontario (p < 0.001). In both provinces, lower patient age, smaller tumour size, a noncentral unifocal tumour, absence of extensive ductal carcinoma in situ and initial surgery by a surgeon with an academic affiliation were associated with greater use of BCS. Lower patient age and larger tumour size were associated with greater use of radiation therapy after BCS in both provinces. CONCLUSION: Patient, tumour and physician factors are associated with the choice of initial management of breast cancer in these two Canadian provinces. However, the differences in management between the two provinces are only partly explained by these factors. Other possible explanations, such as the presence of provincial guidelines, differences in the organization of the health care system or differences in patient preference, require further research. PMID:9006561

Incidence of hemorrhagic stroke in black Caribbean, black African, and white populations: the South London stroke register, 1995-2004.

PubMed

Smeeton, Nigel C; Heuschmann, Peter U; Rudd, Anthony G; McEvoy, Andrew W; Kitchen, Neil D; Sarker, Shah Jalal; Wolfe, Charles D A

2007-12-01

Data are lacking on the differences in hemorrhagic stroke incidence between black Caribbean (BC), black African (BA), and white ethnic groups. We estimated the incidence for primary intracerebral hemorrhage (PICH) and subarachnoid hemorrhage (SAH) and the associated risk factors for BCs, BAs, and whites. First-ever stroke patients were drawn from a prospective community stroke register based in a multiethnic population in South London with 9% BCs, 15% BAs, and 63% whites. Incidence rates were standardized to European and world populations and adjusted for age and sex. Incidence rate ratios (IRRs) relative to whites were calculated by Poisson regression. Between 1995 and 2004, 566 incident stroke patients were registered: 395 PICHs and 171 SAHs. For PICH, age- and sex-adjusted IRRs were higher in BAs (IRR, 2.80; 95% CI, 2.00 to 3.91) than in BCs (IRR, 1.46; 95% CI, 1.07 to 1.99) and were particularly pronounced for patients age 0 to 64 years: IRR=3.95 (95% CI, 2.65 to 5.87) in BAs and 2.38 (95% CI, 1.50 to 3.80) in BCs. For those <65 years, prestroke hypertension was more prevalent in BAs and BCs (P=0.049). For SAH, the IRR was higher in BCs (IRR; 1.62; 95% CI, 1.05 to 2.48) than in BAs (IRR, 0.80; 95% CI, 0.43 to 1.46). The higher incidence of PICH observed in BCs and BAs could be explained by prestroke hypertension being more common among young blacks. The different incidences of SAH in BCs and BAs suggest that the baseline risk of stroke for distinct black ethnic groups is not homogeneous.

In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

PubMed

Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

2014-10-01

Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

A Possible Path from BCS through HTS to VHTS

NASA Astrophysics Data System (ADS)

Chu, C. W.

2010-03-01

Three years after celebrating the 50th anniversary of the BCS theory and the 20th anniversary of the discovery of high temperature superconductivity (HTS), it appears to be most fitting for us to contemplate the possibility of very high temperature superconductivity (VHTS). VHTS, preferably at room temperature, if achieved, could change the world both scientifically and technologically. Unfortunately, it has long been considered by some to belong to the domain of science fiction and to occur only ``at an astronomical distance and under an astronomical pressure.'' With the advent of liquid nitrogen superconductivity in 1987, the outlook has become much brighter. Currently, there appears to be no reason, either theoretical or experimental, why VHTS would be impossible, in spite of the 2006 prediction of the death of HTS by 2010-2015 through the so-called scientometric analysis of the publication record of the previous 20 years. The recent discovery of the new class of Fe-pnictide HTSs fuels more cautious optimism. Since its inception, BCS theory has provided the basic framework for the occurrence and understanding of superconductivity, but it has failed to show where and how to find superconductivity at a higher temperature. This may be attributed to the small energy scale of superconductivity in comparison with those of other excitations in the solids. After examining existing data, we believe that a holistic multidisciplinary enlightened empirical approach appears to be the most effective way to discover novel superconductors with higher transition temperatures. In this talk, I shall present several possible approaches toward VHTS that we are currently pursuing, after briefly summarizing what has happened in the long search for HTS and VHTS.

W-007H B Plant Process Condensate Treatment Facility. Revision 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rippy, G.L.

1995-01-20

B Plant Process Condensate (BCP) liquid effluent stream is the condensed vapors originating from the operation of the B Plant low-level liquid waste concentration system. In the past, the BCP stream was discharged into the soil column under a compliance plan which expired January 1, 1987. Currently, the BCP stream is inactive, awaiting restart of the E-23-3 Concentrator. B Plant Steam Condensate (BCS) liquid effluent stream is the spent steam condensate used to supply heat to the E-23-3 Concentrator. The tube bundles in the E-23-3 Concentrator discharge to the BCS. In the past, the BCS stream was discharged into themore » soil column. Currently, the BCS stream is inactive. This project shall provide liquid effluent systems (BCP/BCS/BCE) capable of operating for a minimum of 20 years, which does not include the anticipated decontamination and decommissioning (D and D) period.« less

Coping with Breast Cancer: Reflections from Chinese-, Korean-, and Mexican-American Women

PubMed Central

Gonzalez, Patricia; Nuñez, Alicia; Wang-Letzkus, Ming; Lim, Jung-Won; Flores, Katrina; Nápoles, Anna María

2015-01-01

Objective The present study identified and compared the coping strategies of Chinese-, Korean-, and Mexican-American breast cancer survivors (BCS). Methods Six focus groups were conducted with Chinese- (n = 21), Korean- (n = 11), and Mexican-American (n = 9) BCS. Interviews were audio-recorded, transcribed, and translated for thematic content analysis of coping experiences and strategies. Results Women reported the use of eight coping strategies (religious/spiritual, benefit finding, fatalism, optimism, fighting spirit, information seeking, denial, and self-distraction). Among Chinese-American BCS, benefit finding was the most referenced coping strategy, whereas religious/spiritual coping was most frequently reported among Korean- and Mexican-American BCS. Denial and self-distraction were the least cited strategies. Conclusions Survivors draw upon new found inner strength to successfully integrate their cancer experience into their lives. Coping models must consider the diversity of cancer survivors and the variability in coping strategies among cultural ethnic minority BCS. PMID:26389720

Accelerated Thermal Depolymerization of Cyclic Polyphthalaldehyde with a Polymeric Thermoacid Generator.

PubMed

Lopez Hernandez, Hector; Lee, Olivia P; Possanza, Catherine; Kaitz, Joshua A; Park, Chan Woo; Plantz, Christopher L; Moore, Jeffrey S; White, Scott R

2018-04-30

Thermally triggerable polymer films that degrade at modest temperatures (≈85 °C) are created from a blend of cyclic polyphthalaldehyde (cPPA) and a polymeric thermoacid generator, poly(vinyl tert-butyl carbonate sulfone) (PVtBCS). PVtBCS depolymerizes when heated, generating acid which initiates the depolymerization of cPPA into volatile byproducts. The mass loss onset for 2 wt% PVtBCS/cPPA is 22 °C lower than the onset for neat cPPA alone in dynamic thermogravimetric analysis experiments. Increased concentrations of PVtBCS increase the rate of depolymerization of cPPA. Raman spectroscopy reveals that the monomer, o-phthalaldehyde, is the main depolymerization product of the acid-catalyzed depolymerization of cPPA. The PVtBCS/cPPA blend is a promising material for the design and manufacture of transient electronic packaging and polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of bovine (Bos indicus) ovarian potential for in vitro embryo production in the Adamawa plateau (Cameroon)

PubMed Central

Kouamo, J.; Dawaye, S.M.; Zoli, A.P.; Bah, G.S.

2014-01-01

An abattoir study was conducted to evaluate the ovarian potential of 201 local zebu cattle from Ngaoundere, Adamawa region (Cameroon) for in vitro embryo production (IVEP). The ovaries were excised, submerged in normal saline solution (0.9%) and transported to the laboratory for a detailed evaluation. Follicles on each ovary were counted, their diameters (Φ) measured and were grouped into 3 categories: small (Φ < 3 mm), medium (3 ≥ Φ ≤ 8 mm) and large (Φ > 8 mm). Each ovary was then sliced into a petri dish; the oocytes were recovered in Dulbecco’s phosphate buffered saline, examined under a stereoscope (x10) and graded into four groups based on the morphology of cumulus oophorus cells and cytoplasmic changes of the oocytes. Grade I (GI): oocytes with more than 4 layers of bunch of compact cumulus cells mass with evenly granulated cytoplasm; grade II (GII): oocyte with at least 2-4 layers of compact cumulus cell mass with evenly granulated cytoplasm; grade III (GIII): oocyte with at least one layer of compact cumulus cell mass with evenly granulated cytoplasm; grade IV (GIV): denuded oocyte with no cumulus cells or incomplete layer of cumulus cell or expanded cells and having dark or unevenly granulated cytoplasm. The effects of both ovarian (ovarian localization, corpus luteum, size and weight of ovary) and non-ovarian factors (breed, age, body condition score (BCS) and pregnancy status of cow) on the follicular population and oocyte recovery rate were determined. There were an average of 16.75±0.83 follicles per ovary. The small, medium and large follicles were 8.39±0.60, 8.14±0.43 and 0.21±0.02 respectively. Oocyte recovery was 10.97±0.43 per ovary (65%). Oocytes graded I, II, III and IV were 3.53±0.19 (32.21%), 2.72±0.15 (24.82%), 2.24±0.15 (20.43%) and 2.47±0.20 (22.54%) respectively. The oocyte quality index was 2.26. Younger non pregnant cows having BCS of 3 and large ovaries presented higher number of follicles and oocyte quality (P < 0.05) compared with other animals. Oocytes with quality (grade I and II) acceptable for IVEP constituted 57.15% of the harvest. This study indicated that factors such as age, pregnancy status, BCS and ovarian size must be taken into account to increase the potential of the ovary for IVEP. PMID:26623353

Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate.

PubMed

Sunazuka, Yushi; Ueda, Keisuke; Higashi, Kenjirou; Tanaka, Yusuke; Moribe, Kunikazu

2018-05-24

We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing Labrafac™ lipophile WL 1349 (WL1349) or Labrafil ® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm. In vitro tests showed that the microemulsion droplets containing M1944 had relatively small FFB solubilization capacities, causing larger amounts of FFB to be dissolved in the bulk water phase, compared to the droplets containing WL1349. The diffusivity of the microemulsion droplets through the mucin solution layer was enhanced when using HCO40 compared to HCO60. The oral absorption in rats was the highest when using the SMEDDS formulation containing M1944 and HCO40. High FFB distribution in the bulk water phase and fast diffusion of microemulsion droplets through the mucus layer contributed to the efficient delivery of FFB molecules through the UWL to the epithelial cells, leading to enhanced FFB absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

A microhydrodynamic rationale for selection of bead size in preparation of drug nanosuspensions via wet stirred media milling.

PubMed

Li, Meng; Alvarez, Paulina; Bilgili, Ecevit

2017-05-30

Although wet stirred media milling has proven to be a robust process for producing nanoparticle suspensions of poorly water-soluble drugs and thereby enhancing their bioavailability, selection of bead size has been largely empirical, lacking fundamental rationale. This study aims to establish such rationale by investigating the impact of bead size at various stirrer speeds on the drug breakage kinetics via a microhydrodynamic model. To this end, stable suspensions of griseofulvin, a model BCS Class II drug, were prepared using hydroxypropyl cellulose and sodium dodecyl sulfate. The suspensions were milled at four different stirrer speeds (1000-4000rpm) using various sizes (50-1500μm) of zirconia beads. Laser diffraction, SEM, and XRPD were used for characterization. Our results suggest that there is an optimal bead size that achieves fastest breakage at each stirrer speed and that it shifts to a smaller size at higher speed. Calculated microhydrodynamic parameters reveal two counteracting effects of bead size: more bead-bead collisions with less energy/force upon a decrease in bead size. The optimal bead size exhibits a negative power-law correlation with either specific energy consumption or the microhydrodynamic parameters. Overall, this study rationalizes the use of smaller beads for more energetic wet media milling. Copyright © 2017 Elsevier B.V. All rights reserved.

Cocrystal of Ibuprofen⁻Nicotinamide: Solid-State Characterization and In Vivo Analgesic Activity Evaluation.

PubMed

Yuliandra, Yori; Zaini, Erizal; Syofyan, Syofyan; Pratiwi, Wenny; Putri, Lidiya Novita; Pratiwi, Yuti Sahra; Arifin, Helmi

2018-06-04

Ibuprofen is classified as a BCS class II drug which has low solubility and high permeability. We conducted the formation of the cocrystalline phase of ibuprofen with coformer nicotinamide to increase its solubility. The purpose of this study was to characterize the solid state of cocrystalline phase of ibuprofen-nicotinamide, determine the solubility, and evaluate its in vivo analgesic activity. The cocrystal of ibuprofen-nicotinamide was prepared by a slow evaporation method. The solid-state characterization was conducted by powder X-ray diffraction (PXRD) analysis, differential thermal analysis (DTA), and scanning electron microscopy (SEM). To investigate the in vivo analgesic activity, 28 male Swiss-Webster mice were injected with acetic acid 0.5% following oral administration of intact ibuprofen, physical mixture, and its cocrystalline phase with nicotinamide (equivalent to 26 mg/kg ibuprofen). The number of writhes was counted, and pain inhibition was calculated. All data were analyzed with one-way ANOVA followed by Duncan's Multiple Range Test (95% confidence interval). The results revealed that a new cocrystalline phase was successfully formed. The solubility testing showed that the cocrystal formation enhanced the solubility significantly as compared with the physical mixture and intact ibuprofen. A significant increase in the analgesic activity of cocrystal ibuprofen-nicotinamide was also confirmed.

Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness

2017-03-30

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures. Copyright © 2017 Elsevier B.V. All rights reserved.

The Bologna complete sample of nearby radio sources. II. Phase referenced observations of faint nuclear sources

NASA Astrophysics Data System (ADS)

Liuzzo, E.; Giovannini, G.; Giroletti, M.; Taylor, G. B.

2009-10-01

Aims: To study statistical properties of different classes of sources, it is necessary to observe a sample that is free of selection effects. To do this, we initiated a project to observe a complete sample of radio galaxies selected from the B2 Catalogue of Radio Sources and the Third Cambridge Revised Catalogue (3CR), with no selection constraint on the nuclear properties. We named this sample “the Bologna Complete Sample” (BCS). Methods: We present new VLBI observations at 5 and 1.6 GHz for 33 sources drawn from a sample not biased toward orientation. By combining these data with those in the literature, information on the parsec-scale morphology is available for a total of 76 of 94 radio sources with a range in radio power and kiloparsec-scale morphologies. Results: The fraction of two-sided sources at milliarcsecond resolution is high (30%), compared to the fraction found in VLBI surveys selected at centimeter wavelengths, as expected from the predictions of unified models. The parsec-scale jets are generally found to be straight and to line up with the kiloparsec-scale jets. A few peculiar sources are discussed in detail. Tables 1-4 are only available in electronic form at http://www.aanda.org

Thermal processing of a poorly water-soluble drug substance exhibiting a high melting point: the utility of KinetiSol® Dispersing.

PubMed

Hughey, Justin R; Keen, Justin M; Brough, Chris; Saeger, Sophie; McGinity, James W

2011-10-31

Poorly water-soluble drug substances that exhibit high melting points are often difficult to successfully process by fusion-based techniques. The purpose of this study was to identify a suitable polymer system for meloxicam (MLX), a high melting point class II BCS compound, and investigate thermal processing techniques for the preparation of chemically stable single phase solid dispersions. Thermal and solution based screening techniques were utilized to screen hydrophilic polymers suitable for immediate release formulations. Results of the screening studies demonstrated that Soluplus(®)(SOL) provided the highest degree of miscibility and solubility enhancement. A hot-melt extrusion feasibility study demonstrated that high temperatures and extended residence times were required in order to render compositions amorphous, causing significant degradation of MLX. A design of experiments (DOE) was conducted on the KinetiSol(®) Dispersing (KSD) process to evaluate the effect of processing conditions on the chemical stability and amorphous character of MLX. The study demonstrated that ejection temperature significantly impacted MLX stability. All samples prepared by KSD were substantially amorphous. Dissolution analysis of the KSD processed solid dispersions showed increased dissolution rates and extent of supersaturation over the marketed generic MLX tablets. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex

PubMed Central

Sravya, Maddukuri; Deveswaran, Rajamanickam; Bharath, Srinivasan; Basavaraj, Basappa Veerbadraiah; Madhavan, Varadharajan

2013-01-01

The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. PMID:26555987

The colors of biomass burning aerosols in the atmosphere.

PubMed

Liu, Chao; Chung, Chul Eddy; Zhang, Feng; Yin, Yan

2016-06-16

Biomass burning aerosols mainly consist of black carbon (BC) and organic aerosols (OAs), and some of OAs are brown carbon (BrC). This study simulates the colors of BrC, BC and their mixture with scattering OAs in the ambient atmosphere by using a combination of light scattering simulations, a two-stream radiative transfer model and a RGB (Red, Green, Blue) color model. We find that both BCs and tar balls (a class of BrC) appear brownish at small particle sizes and blackish at large sizes. This is because the aerosol absorption Ångström exponent (AAE) largely controls the color and larger particles give smaller AAE values. At realistic size distributions, BCs look more blackish than tar balls, but still exhibit some brown color. However, when the absorptance of aerosol layer at green wavelength becomes larger than approximately 0.8, all biomass burning aerosols look blackish. The colors for mixture of purely scattering and absorptive carbonaceous aerosol layers in the atmosphere are also investigated. We suggest that the brownishness of biomass burning aerosols indicates the amount of BC/BrC as well as the ratio of BC to BrC.

Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

PubMed

Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

2012-08-01

A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

MHC class II expression in lung cancer.

PubMed

He, Yayi; Rozeboom, Leslie; Rivard, Christopher J; Ellison, Kim; Dziadziuszko, Rafal; Yu, Hui; Zhou, Caicun; Hirsch, Fred R

2017-10-01

Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). Seven (12.7%) NSCLC cell lines were positive for MHC Class II. No SCLC cell lines were found to be MHC Class II positive. We assessed 139 lung cancer samples available in the Hirsch Lab for MHC Class II. There was no positive MHC Class II staining on SCLC tumor cells. MHC Class II expression on TILs in SCLC was significantly lower than that on TILs in NSCLC (P＜0.001). MHC Class II was also assessed in an additional 139 NSCLC tumor tissues from Medical University of Gdansk, Poland. Patients with positive staining of MHC Class II on TILs had longer regression-free survival (RFS) and overall survival (OS) than those whose TILs were MHC Class II negative (2.980 years, 95% CI 1.628-4.332 vs. 1.050 years, 95% CI 0.556-1.554, P=0.028) (3.230 years, 95% CI 2.617-3.843 vs. 1.390 years, 95% CI 0.629-2.151, P=0.014). MHC Class II was expressed both in NSCLC cell lines and tissues. However, MHC Class II was not detected in SCLC cell lines or tissue tumor cells. MHC Class II expression was lower on SCLC TILs than on NSCLC TILs. Loss of expression of MHC Class II on SCLC tumor cells and reduced expression on SCLC TILs may be a means of escaping anti-cancer immunity. Higher MHC Class II expression on TILs was correlated with better prognosis in patients with NSCLC. Copyright © 2017. Published by Elsevier B.V.

Short-term beta-carotene-supplementation positively affects ovarian activity and serum insulin concentrations in a goat model.

PubMed

Meza-Herrera, C A; Vargas-Beltran, F; Tena-Sempere, M; González-Bulnes, A; Macias-Cruz, U; Veliz-Deras, F G

2013-03-01

In early October 2010, adult goats (no.=22, 3.5 yr old, 7/8 Sannen-Alpine, 26° N, 103° W, at 1117 m), were randomly assigned to: i) beta-carotene group (BC) [no.=10; live weight (LW)=45.9±1.97 kg, body condition score (BCS) =3.04±0.08; orally supplemented with 50 mg of BC per goat per day]; ii) control group (CONT) (no.=12; LW=46.2±2.04 kg, BCS=3.0±0.08). Animals received a basal diet of alfalfa hay, corn silage, and corn grain, having free access to water, shade, and mineral salts. During the second half of October, estrus was synchronized by using intravaginal sponges. Thereafter, by mid-follicular phase, an intensive blood sampling (6 h × 60 min) was performed to evaluate serum insulin concentrations (INS) by radioimmunoassay. By the end of the luteal phase, an ultrasonographic scanning was performed to evaluate total ovarian activity (TOA) [TOA=total follicles (TF) + total corpus luteum (TCL)]. The whole experimental period consisted of 34 days pre- and 17 days post-ovulation, for a total of 52 days. Average LW and BCS did not differ (p>0.05) during the experimental period. Nonetheless, increases in TF no. (5.0 vs 3.4±0.6 units; p=0.05), TCL no. (3.4 vs 2.8±0.2 units; p=0.05), TOA (8.1 vs 6.2±0.6 units; p=0.05) and INS (4.6 vs 3.9±0.4 ng ml-1; p=0.05) favored to the BC-supplemented group. A positive correlation between LW (r(2)=0.42; p=0.04) and BCS (r(2)=0.47; p=0.02) with respect to ovulation rate, was detected. BC-supplementation increased ovarian activity in the female goat while positively affected the release pattern of insulin, suggesting a potential role of BC as a central and/or pancreas-activating molecule in adult goats; such results may hold not only physiologic but also clinical significance. ©2013, Editrice Kurtis

Higgs amplitude mode in the BCS superconductors Nb1-xTi(x)N induced by terahertz pulse excitation.

PubMed

Matsunaga, Ryusuke; Hamada, Yuki I; Makise, Kazumasa; Uzawa, Yoshinori; Terai, Hirotaka; Wang, Zhen; Shimano, Ryo

2013-08-02

Ultrafast responses of BCS superconductor Nb(1-x)Ti(x)N films in a nonadiabatic excitation regime were investigated by using terahertz (THz) pump-THz probe spectroscopy. After an instantaneous excitation with the monocycle THz pump pulse, a transient oscillation emerges in the electromagnetic response in the BCS gap energy region. The oscillation frequency coincides with the asymptotic value of the BCS gap energy, indicating the appearance of the theoretically anticipated collective amplitude mode of the order parameter, namely the Higgs amplitude mode. Our result opens a new pathway to the ultrafast manipulation of the superconducting order parameter by optical means.

Generalized Bose-Einstein Condensation in Superconductivity

NASA Astrophysics Data System (ADS)

de Llano, Manuel

2011-03-01

Unification of the BCS and the Bose-Einstein condensation (BEC) theories is surveyed in detail via a generalized BEC (GBEC) finite-temperature statistical formalism. Its major difference with BCS theory is that it can be diagonalized exactly. Under specified conditions it yields the precise BCS gap equation for all temperatures as well as the precise BCS zero-temperature condensation energy for all couplings, thereby suggesting that a BCS condensate is a BE condensate in a ternary mixture of kinematically independent unpaired electrons coexisting with equally proportioned weakly-bound two-electron and two-hole Cooper pairs. Without abandoning the electron-phonon mechanism in moderately weak coupling it suffices, in principle, to reproduce the unusually high values of Tc (in units of the Fermi temperature TF) of 0.01-0.05 empirically reported in the so-called "exotic" superconductors of the Uemura plot, including cuprates, in contrast to the low values of Tc/TF ≤ 10-3 roughly reproduced by BCS theory for conventional (mostly elemental) superconductors. Replacing the characteristic phonon-exchange Debye temperature by a characteristic magnon-exchange one more than twice in size can lead to a simple interaction model associated with spin-fluctuation-mediated pairing.

Generalized Bose-Einstein Condensation in Superconductivity

NASA Astrophysics Data System (ADS)

de Llano, Manuel

Unification of the BCS and the Bose-Einstein condensation (BEC) theories is surveyed in detail via a generalized BEC (GBEC) finite-temperature statistical formalism. Its major difference with BCS theory is that it can be diagonalized exactly. Under specified conditions it yields the precise BCS gap equation for all temperatures as well as the precise BCS zero-temperature condensation energy for all couplings, thereby suggesting that a BCS condensate is a BE condensate in a ternary mixture of kinematically independent unpaired electrons coexisting with equally proportioned weakly-bound two-electron and two-hole Cooper pairs. Without abandoning the electron-phonon mechanism in moderately weak coupling it suffices, in principle, to reproduce the unusually high values of Tc (in units of the Fermi temperature TF) of 0.01-0.05 empirically reported in the so-called "exotic" superconductors of the Uemura plot, including cuprates, in contrast to the low values of Tc/TF ≤ 10-3 roughly reproduced by BCS theory for conventional (mostly elemental) superconductors. Replacing the characteristic phonon-exchange Debye temperature by a characteristic magnon-exchange one more than twice in size can lead to a simple interaction model associated with spin-fluctuation-mediated pairing.

Breast cancer screening among shift workers: a nationwide population-based survey in Korea.

PubMed

Son, Heesook; Kang, Youngmi

2017-04-01

We aimed to examine the association between shift work types and participation in breast cancer screening (BCS) programs by comparing rates of participation for BCS among regular daytime workers and alternative shift workers using data from a nationally representative, population-based survey conducted in Korea. In addition, the results were analyzed according to sociodemographic factors, including occupation, education, income, private health insurance, age, and number of working hours a week. This secondary cross-sectional analysis used data from the 2012 Korean National Health and Nutritional Examination Survey. The target population included women aged ≥ 40 years who responded as to whether they had undergone BCS in the previous year. Accordingly, we analyzed survey data for a total of 1,193 women and used a multivariate logistic regression analysis to evaluate the differences in factors affecting BCS between regular daytime and alternative shift workers. A logistic regression analysis was performed considering private health insurance as a significant sociodemographic factor for BCS among regular daytime shift workers. In contrast, none of the tested variables could significantly predict adherence to BCS among alternative shift workers. The results of this study suggest the need for the development of comprehensive workplace breast cancer prevention programs by considering shift work types. More attention should be given to female workers with low education levels, those who are uninsured, and young workers to improve the participation rate for BCS at the workplace.

Association of changes among body condition score during the transition period with NEFA and BHBA concentrations, milk production, fertility, and health of Holstein cows.

PubMed

Barletta, R V; Maturana Filho, M; Carvalho, P D; Del Valle, T A; Netto, A S; Rennó, F P; Mingoti, R D; Gandra, J R; Mourão, G B; Fricke, P M; Sartori, R; Madureira, E H; Wiltbank, M C

2017-12-01

Our objective was to evaluate the association between body condition score (BCS) change during the transition period with fertility, non-esterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA) concentrations, milk yield, and health problems of Holstein cows in a retrospective cohort study. Holstein cows (n = 232) were assessed for BCS (5 point scale; 0.25 point increments) and had blood collected at 21 and 7 d before, on the day of, and 7 and 21 d after calving. Blood samples were assayed for NEFA and BHBA concentrations. All cows received a timed artificial insemination (TAI) at 65 ± 3 days in milk (DIM) following a Presynch-Ovsynch protocol with a progesterone implant during the Ovsynch protocol. Cows were grouped based on BCS change after calving as to whether they: 1) lost (L), 2) maintained (M), or 3) gained (G) BCS. Data were analyzed by logistic regression with GLIMMIX and ANOVA with repeated measures using the MIXED procedures of SAS. Both NEFA and BHBA concentrations after calving differed (P < 0.01) for cows that lost, maintained, or gained BCS from 21 d before to 21 d after calving (NEFA: 0.51 ± 0.01; 0.45 ± 0.01; 0.42 ± 0.01 mmol/L; BHBA: 0.73 ± 0.02; 0.70 ± 0.02; 0.68 ± 0.02 mmol/L; respectively; mean ± SEM). By design, BCS change after calving differed (P < 0.01) among groups and was -0.38; 0.00; and 0.35 for cows in groups L, M, and G, respectively. At 21 d before and 21 d after calving, BCS differed (P < 0.01) among groups and was [before (2.97, 2.70, and 2.57) and after (2.54, 2.70, and 2.90)] for cows in groups L, M, and G, respectively. Between evaluated days, higher circulating NEFA and BHBA concentrations were observed 7 d after calving. Change in BCS affected (P < 0.01) pregnancy/AI (P/AI), days to first ovulation, and percentage of cyclic cows at 50 DIM. At 32 d after TAI, P/AI differed (P < 0.01) for cows that lost [18% (11/84)], maintained [33% (26/80)], or gained [47% (32/68)] BCS. Cows that lost BCS during the transition period had more health events (P < 0.01), than cows that gained or maintained BCS. In conclusion, changes in BCS during the transition period affected NEFA and BHBA concentrations, fertility, and occurrence of health problems during the lactation. Copyright © 2017 Elsevier Inc. All rights reserved.

Multidrug- and Extensively Drug-Resistant Uropathogenic Escherichia coli Clinical Strains: Phylogenetic Groups Widely Associated with Integrons Maintain High Genetic Diversity.

PubMed

Ochoa, Sara A; Cruz-Córdova, Ariadnna; Luna-Pineda, Victor M; Reyes-Grajeda, Juan P; Cázares-Domínguez, Vicenta; Escalona, Gerardo; Sepúlveda-González, Ma Eugenia; López-Montiel, Fernanda; Arellano-Galindo, José; López-Martínez, Briceida; Parra-Ortega, Israel; Giono-Cerezo, Silvia; Hernández-Castro, Rigoberto; de la Rosa-Zamboni, Daniela; Xicohtencatl-Cortes, Juan

2016-01-01

In recent years, an increase of uropathogenic Escherichia coli (UPEC) strains with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that complicate therapy for urinary tract infections (UTIs) has been observed and has directly impacted costs and extended hospital stays. The aim of this study was to determine MDR- and XDR-UPEC clinical strains, their virulence genes, their phylogenetic groups and to ascertain their relationship with integrons and genetic diversity. From a collection of 500 UPEC strains, 103 were selected with MDR and XDR characteristics. MDR-UPEC strains were mainly associated with phylogenetic groups D (54.87%) and B2 (39.02%) with a high percentage (≥70%) of several fimbrial genes ( ecpA, fimH, csgA , and papG II), an iron uptake gene ( chuA ), and a toxin gene ( hlyA ). In addition, a moderate frequency (40-70%) of other genes ( iutD, tosA , and bcs A) was observed. XDR-UPEC strains were predominantly associated with phylogenetic groups B2 (47.61%) and D (42.85%), which grouped with ≥80 virulence genes, including ecpA, fimH, csgA, papG II, iutD , and chuA . A moderate frequency (40-70%) of the tosA and hlyA genes was observed. The class 1 and 2 integrons that were identified in the MDR- and XDR-UPEC strains were associated with phylogenetic groups D, B2, and A, while the XDR-UPEC strains that were associated with phylogenetic groups B2, D, and A showed an extended-spectrum beta-lactamase (ESBL) phenotype. The modifying enzymes ( aad A1, aad B, aac C, ant 1, dfr A1, dfr A17, and aad A4) that were identified in the variable region of class 1 and 2 integrons from the MDR strains showed resistance to gentamycin (56.25 and 66.66%, respectively) and trimethoprim-sulfamethoxazole (84.61 and 66.66%, respectively). The MDR- and XDR-UPEC strains were distributed into seven clusters and were closely related to phylogenic groups B2 and D. The diversity analysis by PFGE showed 42.68% of clones of MDR-UPEC and no clonal association in the XDR-UPEC strains. In conclusion, phylogenetic groups including virulence genes are widely associated with two integron classes (1 and 2) in MDR- and XDR-UPEC strains.

25 CFR 522.10 - Individually owned class II and class III gaming operations other than those operating on...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II and class III gaming... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.10 Individually owned class II and class III...

Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

USGS Publications Warehouse

Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

2016-01-01

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

Contrasting evolutionary histories of MHC class I and class II loci in grouse—effects of selection and gene conversion

PubMed Central

Minias, P; Bateson, Z W; Whittingham, L A; Johnson, J A; Oyler-McCance, S; Dunn, P O

2016-01-01

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens. PMID:26860199

The use of biochar substrates for soil reclamation - results of experiments in Northeastern Germany

NASA Astrophysics Data System (ADS)

Lukas, Stefan; Haubold-Rosar, Michael

2017-04-01

After the model of the very fertile "Terra preta do Indio" in Amazonia, the joint project "LaTerra" has been taken up a new technology for the production of organic substrates using biochar as admixture to the composting and fermentation of biomass to test its application for soil improvement, reclamation and remediation purposes. Processing organic materials or residues and the creation of high quality organic soil improving materials will close material cycles and contribute to the value added on a regional scale. This should be an essential part of a sustainable material flow management. The presentation will focus on the application of biochar substrates for the reclamation of sandy soils in Northeastern Germany. Lignite mining activities leave raw soils without humus on dumps and tips. The rapid formation and maintenance of a balanced humus and nutrient budget is of great importance. Field, lysimeter and pot experiments were part of the research program in order to find out the impact of biochar substrate application on soil functions and plant growth and to derive quality criteria and recommendations for practice. The results of the experiments show that application of biochar substrates (BCS) improved soil properties like nutrient supply, organic carbon content, water storage and cation exchange capacity. However, crop yields did not increase in the year of BCS application on the test sites or even decreased on the dumped soil with rising amounts of BCS. This is a consequence of nitrogen immobilization and sorption in the soils treated with BCS. Therefore, BCS applications should be combined with mineral fertilization of nitrogen and BCS production should be modified aiming to improve contents and release of plant available nitrogen. In the third year after BCS application variants treated with 60 t BCS ha-1 (15 Vol.-% biochar) showed highest yields, exceeding the variants with mineral fertilization. On the dumped soil, in the fourth and fifth year after application all variants exceeded yields of mineral fertilization by 5 to 15 % with maximum in variants treated with 90 t BCS (15 Vol.-% biochar) ha-1.

Deposition and weathering of Asian dust in Korea

NASA Astrophysics Data System (ADS)

Jeong, G.

2013-12-01

Paleolithic stone artifacts in Korea typically occur in brown clay-silt (BCS) sequences. The origin and depositional environment of these sequences are important for reconstructing the paleoenvironment as well as for establishing chronologies of artifact-bearing stratigraphic units. We investigated four BCS-bearing sections in foothills and river and marine terraces in Korea by applying quantitative mineralogical, geochemical, microtextural, and K-Ar isotopic methods. In all four sections, the lower units are colluvial and fluvial deposits strongly influenced by diverse local lithology, whereas the upper units are characterized by BCS units. Mineralogical/geochemical compositions, grain sizes, and colors converge into common properties in the upper BCS units in all sections. These common properties are consistent with the eastward trends of increasing weathering degree and grain size fining throughout the loess-paleosol sections of the Chinese Loess Plateau (CLP). K-Ar detrital ages of the sections also converge upward into a narrow range similar to the age ranges of the loess and paleosols in the CLP. The top BCS unit in the Jeongok section, the thickest section, is underlain by an additionally weathered BCS unit, with strong red chroma indicating a change from warm to cold climate. We did not observe any clear evidence of climatic changes in other thinner sections, which may be due to a superposition of cold-stage accumulation and warm-stage deep weathering. The common properties of the BCSs in Korean sections and their relationship to the CLP loess and paleosols indicate widespread deposition of Asian dust and subsequent weathering in the late Quaternary, forming BCS sequences. In this respect, the BCS sequences investigated here are considered to be the additionally weathered equivalents of the CLP loess-paleosol sequences, having been exposed to the high annual precipitation of the Korean Peninsula. Given the wide distribution of BCS sequences at Paleolithic sites throughout the Peninsula, the findings of this study are important for the ongoing debate surrounding the depositional environments of the Paleolithic deposits, and provide a foundation for the establishment of the chronological framework of the Paleolithic artifact-bearing layers and lithic assemblages.

Deposition and weathering of Asian dust in Paleolithic sites, Korea

NASA Astrophysics Data System (ADS)

Jeong, Gi Young; Choi, Jeong-Heon; Lim, Hyoun Soo; Seong, Chuntaek; Yi, Seon Bok

2013-10-01

Paleolithic stone artifacts in Korea typically occur in brown clay-silt (BCS) sequences. The origin and depositional environment of these sequences are important for reconstructing the paleoenvironment as well as for establishing chronologies of artifact-bearing stratigraphic units. We investigated four BCS-bearing sections in foothills and river and marine terraces in Korea by applying quantitative mineralogical, geochemical, microtextural, and K-Ar isotopic methods. In all four sections, the lower units are colluvial and fluvial deposits strongly influenced by diverse local lithology, whereas the upper units are characterized by BCS units. Mineralogical/geochemical compositions, grain sizes, and colors converge into common properties in the upper BCS units in all sections. These common properties are consistent with the eastward trends of increasing weathering degree and grain size fining throughout the loess-paleosol sections of the Chinese Loess Plateau (CLP). K-Ar detrital ages of the sections also converge upward into a narrow range similar to the age ranges of the loess and paleosols in the CLP. The top BCS unit in the Jeongok section, the thickest section, is underlain by an additionally weathered BCS unit, with strong red chroma indicating a change from warm to cold climate. We did not observe any clear evidence of climatic changes in other thinner sections, which may be due to a superposition of cold-stage accumulation and warm-stage deep weathering. The common properties of the BCSs in Korean sections and their relationship to the CLP loess and paleosols indicate widespread deposition of Asian dust and subsequent weathering in the late Quaternary, forming BCS sequences. In this respect, the BCS sequences investigated here are considered to be the additionally weathered equivalents of the CLP loess-paleosol sequences, having been exposed to the high annual precipitation of the Korean Peninsula. Given the wide distribution of BCS sequences at Paleolithic sites throughout the Peninsula, the findings of this study are important for the ongoing debate surrounding the depositional environments of the Paleolithic deposits, and provide a foundation for the establishment of the chronological framework of the Paleolithic artifact-bearing layers and lithic assemblages.

Rear shape in 3 dimensions summarized by principal component analysis is a good predictor of body condition score in Holstein dairy cows.

PubMed

Fischer, A; Luginbühl, T; Delattre, L; Delouard, J M; Faverdin, P

2015-07-01

Body condition is an indirect estimation of the level of body reserves, and its variation reflects cumulative variation in energy balance. It interacts with reproductive and health performance, which are important to consider in dairy production but not easy to monitor. The commonly used body condition score (BCS) is time consuming, subjective, and not very sensitive. The aim was therefore to develop and validate a method assessing BCS with 3-dimensional (3D) surfaces of the cow's rear. A camera captured 3D shapes 2 m from the floor in a weigh station at the milking parlor exit. The BCS was scored by 3 experts on the same day as 3D imaging. Four anatomical landmarks had to be identified manually on each 3D surface to define a space centered on the cow's rear. A set of 57 3D surfaces from 56 Holstein dairy cows was selected to cover a large BCS range (from 0.5 to 4.75 on a 0 to 5 scale) to calibrate 3D surfaces on BCS. After performing a principal component analysis on this data set, multiple linear regression was fitted on the coordinates of these surfaces in the principal components' space to assess BCS. The validation was performed on 2 external data sets: one with cows used for calibration, but at a different lactation stage, and one with cows not used for calibration. Additionally, 6 cows were scanned once and their surfaces processed 8 times each for repeatability and then these cows were scanned 8 times each the same day for reproducibility. The selected model showed perfect calibration and a good but weaker validation (root mean square error=0.31 for the data set with cows used for calibration; 0.32 for the data set with cows not used for calibration). Assessing BCS with 3D surfaces was 3 times more repeatable (standard error=0.075 versus 0.210 for BCS) and 2.8 times more reproducible than manually scored BCS (standard error=0.103 versus 0.280 for BCS). The prediction error was similar for both validation data sets, indicating that the method is not less efficient for cows not used for calibration. The major part of reproducibility error incorporates repeatability error. An automation of the anatomical landmarks identification is required, first to allow broadband measures of body condition and second to improve repeatability and consequently reproducibility. Assessing BCS using 3D imaging coupled with principal component analysis appears to be a very promising means of improving precision and feasibility of this trait measurement. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dynamical instability of a driven-dissipative electron-hole condensate in the BCS-BEC crossover region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanai, Ryo; Littlewood, Peter B.; Ohashi, Yoji

2017-09-01

We present a stability analysis on a driven-dissipative electron-hole condensate in the BCS (Bardeen-Cooper-Schrieffer)-BEC (Bose-Einstein-condensation)-crossover region. Extending the combined BCS-Leggett theory with the generalized random phase approximation (GRPA) to the non-equilibrium case by employing the Keldysh formalism, we show that the pumping-and-decay of carriers causes a depairing effect on excitons. This phenomenon gives rise to an attractive interaction between excitons in the BEC regime, as well as a supercurrent that anomalously flows anti-parallel to ∇θ(r) (where θ(r) is the phase of the condensate) in the BCS regime, both leading to dynamical instabilities of an exciton-BEC.

Superconductivity in an electron band just above the Fermi level: possible route to BCS-BEC superconductivity.

PubMed

Okazaki, K; Ito, Y; Ota, Y; Kotani, Y; Shimojima, T; Kiss, T; Watanabe, S; Chen, C-T; Niitaka, S; Hanaguri, T; Takagi, H; Chainani, A; Shin, S

2014-02-28

Conventional superconductivity follows Bardeen-Cooper-Schrieffer(BCS) theory of electrons-pairing in momentum-space, while superfluidity is the Bose-Einstein condensation(BEC) of atoms paired in real-space. These properties of solid metals and ultra-cold gases, respectively, are connected by the BCS-BEC crossover. Here we investigate the band dispersions in FeTe(0.6)Se(0.4)(Tc = 14.5 K ~ 1.2 meV) in an accessible range below and above the Fermi level(EF) using ultra-high resolution laser angle-resolved photoemission spectroscopy. We uncover an electron band lying just 0.7 meV (~8 K) above EF at the Γ-point, which shows a sharp superconducting coherence peak with gap formation below Tc. The estimated superconducting gap Δ and Fermi energy [Symbol: see text]F indicate composite superconductivity in an iron-based superconductor, consisting of strong-coupling BEC in the electron band and weak-coupling BCS-like superconductivity in the hole band. The study identifies the possible route to BCS-BEC superconductivity.

STRUCTURAL ESTIMATES OF TREATMENT EFFECTS ON OUTCOMES USING RETROSPECTIVE DATA: AN APPLICATION TO DUCTAL CARCINOMA IN SITU

PubMed Central

Gold, Heather Taffet; Sorbero, Melony E. S.; Griggs, Jennifer J.; Do, Huong T.; Dick, Andrew W.

2013-01-01

Analysis of observational cohort data is subject to bias from unobservable risk selection. We compared econometric models and treatment effectiveness estimates using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data for women diagnosed with ductal carcinoma in situ. Treatment effectiveness estimates for mastectomy and breast conserving surgery (BCS) with or without radiotherapy were compared using three different models: simultaneous-equations model, discrete-time survival model with unobserved heterogeneity (frailty), and proportional hazards model. Overall trends in disease-free survival (DFS), or time to first subsequent breast event, by treatment are similar regardless of the model, with mastectomy yielding the highest DFS over 8 years of follow-up, followed by BCS with radiotherapy, and then BCS alone. Absolute rates and direction of bias varied substantially by treatment strategy. DFS was underestimated by single-equation and frailty models compared to the simultaneous-equations model and RCT results for BCS with RT and overestimated for BCS alone. PMID:21602195

Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose.

PubMed

Thongsomboon, Wiriya; Serra, Diego O; Possling, Alexandra; Hadjineophytou, Chris; Hengge, Regine; Cegelski, Lynette

2018-01-19

Cellulose is a major contributor to the chemical and mechanical properties of plants and assumes structural roles in bacterial communities termed biofilms. We find that Escherichia coli produces chemically modified cellulose that is required for extracellular matrix assembly and biofilm architecture. Solid-state nuclear magnetic resonance spectroscopy of the intact and insoluble material elucidates the zwitterionic phosphoethanolamine modification that had evaded detection by conventional methods. Installation of the phosphoethanolamine group requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane signaling pathway. The bcsEFG operon is present in many bacteria, including Salmonella species, that also produce the modified cellulose. The discovery of phosphoethanolamine cellulose and the genetic and molecular basis for its production offers opportunities to modulate its production in bacteria and inspires efforts to biosynthetically engineer alternatively modified cellulosic materials. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Red blood cell depletion from bone marrow and peripheral blood buffy coat: a comparison of two new and three established technologies.

PubMed

Sorg, Nadine; Poppe, Carolin; Bunos, Milica; Wingenfeld, Eva; Hümmer, Christiane; Krämer, Ariane; Stock, Belinda; Seifried, Erhard; Bonig, Halvard

2015-06-01

Red blood cell (RBC) depletion is a standard technique for preparation of ABO-incompatible bone marrow transplants (BMTs). Density centrifugation or apheresis are used successfully at clinical scale. The advent of a bone marrow (BM) processing module for the Spectra Optia (Terumo BCT) provided the initiative to formally compare our standard technology, the COBE2991 (Ficoll, manual, "C") with the Spectra Optia BMP (apheresis, semiautomatic, "O"), the Sepax II NeatCell (Ficoll, automatic, "S"), the Miltenyi CliniMACS Prodigy density gradient separation system (Ficoll, automatic, "P"), and manual Ficoll ("M"). C and O handle larger product volumes than S, P, and M. Technologies were assessed for RBC depletion, target cell (mononuclear cells [MNCs] for buffy coats [BCs], CD34+ cells for BM) recovery, and cost/labor. BC pools were simultaneously purged with C, O, S, and P; five to 18 BM samples were sequentially processed with C, O, S, and M. Mean RBC removal with C was 97% (BCs) or 92% (BM). From both products, O removed 97%, and P, S, and M removed 99% of RBCs. MNC recovery from BC (98% C, 97% O, 65% P, 74% S) or CD34+ cell recovery from BM (92% C, 90% O, 67% S, 70% M) were best with C and O. Polymorphonuclear cells (PMNs) were depleted from BCs by P, S, and C, while O recovered 50% of PMNs. Time savings compared to C or M for all tested technologies are considerable. All methods are in principle suitable and can be selected based on sample volume, available technology, and desired product specifications beyond RBC depletion and MNC and/or CD34+ cell recovery. © 2015 AABB.

Quantifying the Chasm: Exploring the Impact of the BCS on Total Football Revenues for Division One Football Programs from 2002-2012

ERIC Educational Resources Information Center

Caro, Cary A.

2014-01-01

The Bowl Championship Series served as a collection of bowl games that were designed to crown the national champion in Division One football. The BCS created two classifications of institutions in Division football, those that were granted automatic access (AQ) to the post-season games, and those that were not (non-AQ). The BCS also generated…

The role of a lack of social integration in never having undergone breast cancer screening: results from a population-based, representative survey in the Paris metropolitan area in 2010.

PubMed

Rondet, Claire; Soler, Marion; Ringa, Virginie; Parizot, Isabelle; Chauvin, Pierre

2013-10-01

This study aims to investigate the association between social contact and social support and women's breast cancer screening (BCS) practices, taking their socioeconomic status (SES) into account. The SIRS survey was conducted in 2010 in the Paris metropolitan area among a representative sample of 3000 French-speaking adults. For the 784 women aged 50years or older with no history of breast cancer, multivariate logistic regressions and bootstrap methods were used to analyze the factors associated with never having undergone BCS. 6.5% of these women had never undergone BCS. In multivariate analysis, being older, having a low education level, having poor-quality health insurance, and having one or less than one social contact per 3-day period were significantly associated with never having undergone BCS during their lifetime, but the level of social support was not. The strength of the association with a low frequency of social contact tended to increase with age. This study analyzed the role of social contact in social inequalities in BCS practices in the Paris metropolitan area. Like SES, social integration and social isolation should be taken into consideration by public health professionals and practitioners when planning BCS programs and incentives. © 2013.

Developing spiritually framed breast cancer screening messages in consultation with African American women.

PubMed

Best, Alicia L; Spencer, Mindi; Hall, Ingrid J; Friedman, Daniela B; Billings, Deborah

2015-01-01

Despite efforts to increase breast cancer screening (BCS) among African American women, disparities in breast cancer mortality persist. Culturally framed health communication may provide a useful strategy to address this issue. Spirituality not only represents an integral aspect of African American culture, but it has also been identified as a potential barrier to BCS among this population. Rather than continuing to focus on spirituality as a barrier, there is an opportunity to develop promotional messages that tap into the protective properties of spirituality among this population. The goals of this study were to engage a group of African American women to identify important spiritual elements to be included in health communication materials, and to subsequently develop a spiritually framed BCS message in response to their feedback. Three nominal group sessions were conducted with 15 African American women. Results revealed three important spiritual elements that can be incorporated into BCS health messages: (a) the body as a temple; (b) going to the doctor does not make you faithless; and (c) God did not give us the spirit of fear. These elements were used to draft a spiritually framed BCS message. Next, 20 face-to-face semistructured interviews were conducted to help finalize the spiritually framed BCS message for use in a future study on culturally framed health communication.

The prognostic value of node status in different breast cancer subtypes

PubMed Central

Hou, Xin-Wei; Chi, Jiang-Rui; Ge, Jie; Wang, Xin; Cao, Xu-Chen

2017-01-01

Nodal metastases and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. However, the association between nodal metastases and BCS, and the prognostic value of nodal metastases in different BCS are still remains unclear. Our aim was to investigate the association between nodal metastases and BCS, and the prognostic value of nodal metastases in the different BCS. We found that the breast cancer subtype was closely associated with the pN stage. pN stage and breast cancer subtype were significantly associated with disease-free survival. The subgroup analysis showed that the patients in higher pN stage had a poor outcome than patients in lower pN stage in each breast cancer subtype. Furthermore, when the analysis was stratified by breast cancer subtype, we found that even in the same pN stage (pN0-pN2), there was significant survival difference among patients in different BCS, and Luminal A breast cancer patients had the best survival outcome. However, there were no significant survival difference between Luminal A patients and other breast cancer subtype when patients in pN3 stage. Thus, our study suggested that both lymph node status and molecular subtype played important roles in the outcome of breast cancer patients and they cannot replace each other. PMID:27999188

Causes of Adult Splanchnic Vein Thrombosis in the Mediterranean Area

PubMed Central

De Stefano, Valerio; Za, Tommaso; Ciminello, Angela; Betti, Silvia; Rossi, Elena

2011-01-01

The term splanchnic vein thrombosis encompasses Budd-Chiari syndrome (BCS), extrahepatic portal vein obstruction (EHPVO), and mesenteric vein thrombosis. Risk factors can be local or systemic. A local precipitating factor is rare in BCS, while it is common in patients with portal vein thrombosis. Chronic myeloproliferative neoplasms (MPN) are the leading systemic cause of splanchnic vein thrombosis, and are diagnosed in half BCS patients and one-third of EHPVO patients; the somatic mutation JAK2 V617F is detectable in a large majority of patients with overt MPN, and up to 40% of patients without overt MPN. Inherited thrombophilia is present in at least one-third of patients, and the factor V Leiden or the prothrombin G20210A mutations are the most common mutations found in BCS or EHPVO patients, respectively. Multiple factors are present in approximately one-third of patients with BCS and two- thirds of patients with portal vein thrombosis. In a few patient series from the Southern Mediterranean area the high prevalence of MPN and thrombophilia as underlying cause of BCS is confirmed, although the data should be considered preliminary. Peculiar risk factors present in the area are Behçet’s disease and hydatidosis; moreover, membraneous webs, typically found in Asian patients, are present in a significant portion of cases. PMID:22220260

Evolution of accesses to information on breast cancer and screening on the Brazilian National Cancer Institute website: an exploratory study.

PubMed

Vasconcellos-Silva, Paulo Roberto; Sormunen, Taina; Craftman, Åsa Gransjön

2018-04-01

Delays in diagnosis due to low Breast Cancer awareness are widespread in Brazil maybe owing to ineffective strategies to raise attention on early diagnosis. As a proxy of collective interest in BC screanning (BCS) we studied the monthly accesses to BC and BCS webpages in INCA's website along 48 months. A log analyzer built a time serie (2006-2009) of BC and BCS monthly means, which oscilations were studied by analysis of variance (ANOVA). We found significant increasing accesses to BC and transient "attention peaks". Enlargement in BC/BCS differences along all period were caused by increasing accesses to BC and decreasing/minor/stable oscillations to SBC pages. These results are consistent with previous reports on increasing interest to BC contrasting with indifference on BCS. In the context of an exploratory study, we discussed some aspects: weakness of a "prevention culture"; lack of confidence in health system and screening programs; "celebrity effect" in the context of media framing; collective perception of risks heightened by perception of social vulnerability. Findings suggest that culture-tailored communication strategies would be necessary to inform Brazilian people about BCS. Future research is needed to study social perceptions and constructions on BC topics.

Evaluation of four microbial Class II fructose 1,6-bisphosphate aldolase enzymes for use as biocatalysts.

PubMed

Labbé, Geneviève; de Groot, Sarah; Rasmusson, Timothy; Milojevic, Gorica; Dmitrienko, Gary I; Guillemette, J Guy

2011-12-01

Fructose 1,6-bisphosphate (FBP) aldolase has been used as biocatalyst in the synthesis of several pharmaceutical compounds such as monosaccharides and analogs. Is has been suggested that microbial metal-dependant Class II aldolases could be better industrial catalysts than mammalian Class I enzyme because of their greater stability. The Class II aldolases from four microbes were subcloned into the Escherichia coli vector pT7-7, expressed and purified to near homogeneity. The kinetic parameters, temperature stability, pH profile, and tolerance to organic solvents of the Class II enzymes were determined, and compared with the properties of the Class I aldolase from rabbit muscle. Contrary to results obtained previously with the E. coli Class II aldolase, which was reported to be more stable than the mammalian enzyme, other recombinant Class II aldolases were found to be generally less stable than the Class I enzyme, especially in the presence of organic solvents. Class II aldolase from Bacillus cereus showed higher temperature stability than the other enzymes tested, but only the Mycobacterium tuberculosis Class II aldolase had a stability comparable to the Class I mammalian enzyme under assay conditions. The turnover number of the recombinant M. tuberculosis and Magnaporthe grisea Class II type A aldolases was comparable or higher than that of the Class I enzyme. The recombinant B. cereus and Pseudomonas aeruginosa Class II type B aldolases had very low turnover numbers and low metal content, indicating that the E. coli overexpression system may not be suitable for the Class II type B aldolases from these microorganisms. Copyright © 2011 Elsevier Inc. All rights reserved.

The association of ruminal pH and some metabolic parameters with conception rate at first artificial insemination in Thai dairy cows.

PubMed

Inchaisri, Chaidate; Chanpongsang, Somchai; Noordhuizen, Jos; Hogeveen, Henk

2013-06-01

The objective of this study was to determine the association of metabolic parameters and cow associated factors with the conception rate at first insemination (FCR) in Thai dairy cows. The investigation was performed with 529 lactations from 32 smallholder dairy farms. At 3-6 weeks after parturition, blood samples and ruminal fluid were collected. Body condition scores (BCS) of cows were scored 1 week before expected calving date and at blood sampling date. Ruminal pH was measured at 2-4 h after morning feeding in ruminal fluid collected by ruminocentesis. Serum beta-hydroxybutyrate and serum urea nitrogen were measured by kinetic enzyme method. Cows with first insemination (AI) between 41 and 114 days postpartum were identified after pregnancy diagnosis for FCR. Breed, parity, interval from calving to first AI, BCS before calving, BCS after calving, loss in BCS after calving, SBHB, SUN, ruminal pH, and postpartum problems were selected as independent variables for a model with FCR as a dependent variable. A multivariable logistic regression model was used with farm as a random effect. Overall FCR was 27.2 %. The FCR depended on interval from calving to first AI, BCS before calving, and ruminal pH. The FCR between 69 and 91 days postpartum was significantly highest (45 %). Before calving, a cow with high BCS (≥ 3.5) had significantly greater FCR than a cow with low BCS (≤ 3.25; P<0.01). An increased ruminal pH raised significantly FCR (OR=2.53; P=0.03).

Influences of barriers to cessation and reasons for quitting on substance use among treatment-seeking smokers who report heavy drinking

PubMed Central

Foster, Dawn W.; Schmidt, Norman B.; Zvolensky, Michael J.

2015-01-01

Objectives We examined behavioral and cognitively-based quit processes among concurrent alcohol and tobacco users and assessed whether smoking and drinking were differentially influenced. Methods Participants were 200 treatment-seeking smokers (37.50% female; Mage = 30.72; SD = 12.68) who reported smoking an average of 10 or more cigarettes daily for at least one year. Results Barriers to cessation (BCS) and reasons for quitting (RFQ) were generally correlated with substance use. BCS moderated the relationship between quit methods and cigarette use such that quit methods were negatively associated with smoking, particularly among those with more BCS. RFQ moderated the association between quit methods and cigarette use such that quit methods were negatively linked with smoking among those with fewer RFQ, but positively linked with smoking among those with more RFQ. Two 3-way interactions emerged. The first 3-way indicated that among individuals with fewer RFQ, quit methods was negatively associated with smoking, and this was strongest among those with more BCS. However, among those with more RFQ, smoking and quit methods were positively associated, particularly among those with more BCS. The second 3-way showed that among those with fewer RFQ, quit methods was negatively linked with drinking frequency, and this was strongest among those with more BCS. However, among those with fewer BCS, drinking and quit methods were positively linked. Conclusions The relationship between behavioral and cognitively-based quit processes and substance use is not straightforward. There may be concurrent substance-using individuals for whom these processes might be associated with increased substance use. PMID:26949566

Barnacle Balanus amphitrite adheres by a stepwise cementing process.

PubMed

Burden, Daniel K; Barlow, Daniel E; Spillmann, Christopher M; Orihuela, Beatriz; Rittschof, Daniel; Everett, R K; Wahl, Kathryn J

2012-09-18

Barnacles adhere permanently to surfaces by secreting and curing a thin interfacial adhesive underwater. Here, we show that the acorn barnacle Balanus amphitrite adheres by a two-step fluid secretion process, both contributing to adhesion. We found that, as barnacles grow, the first barnacle cement secretion (BCS1) is released at the periphery of the expanding base plate. Subsequently, a second, autofluorescent fluid (BCS2) is released. We show that secretion of BCS2 into the interface results, on average, in a 2-fold increase in adhesive strength over adhesion by BCS1 alone. The two secretions are distinguishable both spatially and temporally, and differ in morphology, protein conformation, and chemical functionality. The short time window for BCS2 secretion relative to the overall area increase demonstrates that it has a disproportionate, surprisingly powerful, impact on adhesion. The dramatic change in adhesion occurs without measurable changes in interface thickness and total protein content. A fracture mechanics analysis suggests the interfacial material's modulus or work of adhesion, or both, were substantially increased after BCS2 secretion. Addition of BCS2 into the interface generates highly networked amyloid-like fibrils and enhanced phenolic content. Both intertwined fibers and phenolic chemistries may contribute to mechanical stability of the interface through physically or chemically anchoring interface proteins to the substrate and intermolecular interactions. Our experiments point to the need to reexamine the role of phenolic components in barnacle adhesion, long discounted despite their prevalence in structural membranes of arthropods and crustaceans, as they may contribute to chemical processes that strengthen adhesion through intermolecular cross-linking.

Surveillance cultures of samples obtained from biopsy channels and automated endoscope reprocessors after high-level disinfection of gastrointestinal endoscopes

PubMed Central

2012-01-01

Background The instrument channels of gastrointestinal (GI) endoscopes may be heavily contaminated with bacteria even after high-level disinfection (HLD). The British Society of Gastroenterology guidelines emphasize the benefits of manually brushing endoscope channels and using automated endoscope reprocessors (AERs) for disinfecting endoscopes. In this study, we aimed to assess the effectiveness of decontamination using reprocessors after HLD by comparing the cultured samples obtained from biopsy channels (BCs) of GI endoscopes and the internal surfaces of AERs. Methods We conducted a 5-year prospective study. Every month random consecutive sampling was carried out after a complete reprocessing cycle; 420 rinse and swabs samples were collected from BCs and internal surface of AERs, respectively. Of the 420 rinse samples collected from the BC of the GI endoscopes, 300 were obtained from the BCs of gastroscopes and 120 from BCs of colonoscopes. Samples were collected by flushing the BCs with sterile distilled water, and swabbing the residual water from the AERs after reprocessing. These samples were cultured to detect the presence of aerobic and anaerobic bacteria and mycobacteria. Results The number of culture-positive samples obtained from BCs (13.6%, 57/420) was significantly higher than that obtained from AERs (1.7%, 7/420). In addition, the number of culture-positive samples obtained from the BCs of gastroscopes (10.7%, 32/300) and colonoscopes (20.8%, 25/120) were significantly higher than that obtained from AER reprocess to gastroscopes (2.0%, 6/300) and AER reprocess to colonoscopes (0.8%, 1/120). Conclusions Culturing rinse samples obtained from BCs provides a better indication of the effectiveness of the decontamination of GI endoscopes after HLD than culturing the swab samples obtained from the inner surfaces of AERs as the swab samples only indicate whether the AERs are free from microbial contamination or not. PMID:22943739

Body image and quality of life in patients with and without body contouring surgery following bariatric surgery: a comparison of pre- and post-surgery groups

PubMed Central

de Zwaan, Martina; Georgiadou, Ekaterini; Stroh, Christine E.; Teufel, Martin; Köhler, Hinrich; Tengler, Maxi; Müller, Astrid

2014-01-01

Background: Massive weight loss (MWL) following bariatric surgery frequently results in an excess of overstretched skin causing physical discomfort and negatively affecting quality of life, self-esteem, body image, and physical functioning. Methods: In this cross-sectional study 3 groups were compared: (1) patients prior to bariatric surgery (n = 79), (2) patients after bariatric surgery who had not undergone body contouring surgery (BCS) (n = 252), and (3) patients after bariatric surgery who underwent subsequent BCS (n = 62). All participants completed self-report questionnaires assessing body image (Multidimensional Body-Self Relations Questionnaire, MBSRQ), quality of life (IWQOL-Lite), symptoms of depression (PHQ-9), and anxiety (GAD-7). Results: Overall, 62 patients (19.2%) reported having undergone a total of 90 BCS procedures. The most common were abdominoplasties (88.7%), thigh lifts (24.2%), and breast lifts (16.1%). Post-bariatric surgery patients differed significantly in most variables from pre-bariatric surgery patients. Although there were fewer differences between patients with and without BCS, patients after BCS reported better appearance evaluation (AE), body area satisfaction (BAS), and physical functioning, even after controlling for excess weight loss and time since surgery. No differences were found for symptoms of depression and anxiety, and most other quality of life and body image domains. Discussion: Our results support the results of longitudinal studies demonstrating significant improvements in different aspects of body image, quality of life, and general psychopathology after bariatric surgery. Also, we found better AE and physical functioning in patients after BCS following bariatric surgery compared to patients with MWL after bariatric surgery who did not undergo BCS. Overall, there appears to be an effect of BCS on certain aspects of body image and quality of life but not on psychological aspects on the whole. PMID:25477839

Surveillance cultures of samples obtained from biopsy channels and automated endoscope reprocessors after high-level disinfection of gastrointestinal endoscopes.

PubMed

Chiu, King-Wah; Tsai, Ming-Chao; Wu, Keng-Liang; Chiu, Yi-Chun; Lin, Ming-Tzung; Hu, Tsung-Hui

2012-09-03

The instrument channels of gastrointestinal (GI) endoscopes may be heavily contaminated with bacteria even after high-level disinfection (HLD). The British Society of Gastroenterology guidelines emphasize the benefits of manually brushing endoscope channels and using automated endoscope reprocessors (AERs) for disinfecting endoscopes. In this study, we aimed to assess the effectiveness of decontamination using reprocessors after HLD by comparing the cultured samples obtained from biopsy channels (BCs) of GI endoscopes and the internal surfaces of AERs. We conducted a 5-year prospective study. Every month random consecutive sampling was carried out after a complete reprocessing cycle; 420 rinse and swabs samples were collected from BCs and internal surface of AERs, respectively. Of the 420 rinse samples collected from the BC of the GI endoscopes, 300 were obtained from the BCs of gastroscopes and 120 from BCs of colonoscopes. Samples were collected by flushing the BCs with sterile distilled water, and swabbing the residual water from the AERs after reprocessing. These samples were cultured to detect the presence of aerobic and anaerobic bacteria and mycobacteria. The number of culture-positive samples obtained from BCs (13.6%, 57/420) was significantly higher than that obtained from AERs (1.7%, 7/420). In addition, the number of culture-positive samples obtained from the BCs of gastroscopes (10.7%, 32/300) and colonoscopes (20.8%, 25/120) were significantly higher than that obtained from AER reprocess to gastroscopes (2.0%, 6/300) and AER reprocess to colonoscopes (0.8%, 1/120). Culturing rinse samples obtained from BCs provides a better indication of the effectiveness of the decontamination of GI endoscopes after HLD than culturing the swab samples obtained from the inner surfaces of AERs as the swab samples only indicate whether the AERs are free from microbial contamination or not.

25 CFR 547.3 - What are the definitions for this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.3 What are the... Commission. Class II game. The same as “class II gaming” in 25 U.S.C. 2703(7)(A). Class II gaming system. All..., that function together to aid the play of one or more Class II games, including accounting functions...

25 CFR 547.3 - What are the definitions for this part?

Code of Federal Regulations, 2012 CFR

2012-04-01

... TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.3 What are the... Commission. Class II game. The same as “class II gaming” in 25 U.S.C. 2703(7)(A). Class II gaming system. All..., that function together to aid the play of one or more Class II games, including accounting functions...

25 CFR 547.3 - What are the definitions for this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.3 What are the... Commission. Class II game. The same as “class II gaming” in 25 U.S.C. 2703(7)(A). Class II gaming system. All..., that function together to aid the play of one or more Class II games, including accounting functions...

Impact of plant matrix polysaccharides on cellulose produced by surface-tethered cellulose synthases.

PubMed

Basu, Snehasish; Omadjela, Okako; Zimmer, Jochen; Catchmark, Jeffrey M

2017-04-15

Surface immobilized BcsA-B cellulose synthases synthesize crystalline cellulose II under in vitro conditions and were used to explore the interaction between cellulose and hemicelluloses and pectin. The morphology of the cellulose microfibrils changed in the presence of xyloglucan and glucomannan, while pectin did not significantly impact morphology. X-ray diffractometry and FT-IR spectroscopy indicated that crystal size and crystallinity were significantly affected by xyloglucan and glucomannan but not altered by pectin. Glucomannan had the most significant impact on the structure of cellulose and inhibits crystallization. The presence of xyloglucan and glucomannan prevents the proper assembly of cellulose microfibrils and changes the crystalline properties of cellulose II in in vitro conditions, but did not have any impact on cellulose allomorph. Copyright © 2017 Elsevier Ltd. All rights reserved.

Body condition score and plane of nutrition prepartum affect adipose tissue transcriptome regulators of metabolism and inflammation in grazing dairy cows during the transition period.

PubMed

Vailati-Riboni, M; Kanwal, M; Bulgari, O; Meier, S; Priest, N V; Burke, C R; Kay, J K; McDougall, S; Mitchell, M D; Walker, C G; Crookenden, M; Heiser, A; Roche, J R; Loor, J J

2016-01-01

Recent studies demonstrating a higher incidence of metabolic disorders after calving have challenged the management practice of increasing dietary energy density during the last ~3 wk prepartum. Despite our knowledge at the whole-animal level, the tissue-level mechanisms that are altered in response to feeding management prepartum remain unclear. Our hypothesis was that prepartum body condition score (BCS), in combination with feeding management, plays a central role in the peripartum changes associated with energy balance and inflammatory state. Twenty-eight mid-lactation grazing dairy cows of mixed age and breed were randomly allocated to 1 of 4 treatment groups in a 2 × 2 factorial arrangement: 2 prepartum BCS categories (4.0 and 5.0, based on a 10-point scale; BCS4, BCS5) obtained via differential feeding management during late-lactation, and 2 levels of energy intake during the 3 wk preceding calving (75 and 125% of estimated requirements). Subcutaneous adipose tissue was harvested via biopsy at -1, 1, and 4 wk relative to parturition. Quantitative polymerase chain reaction was used to measure mRNA and microRNA (miRNA) expression of targets related to fatty acid metabolism (lipogenesis, lipolysis), adipokine synthesis, and inflammation. Both prepartum BCS and feeding management had a significant effect on mRNA and miRNA expression throughout the peripartum period. Overfed BCS5 cows had the greatest prepartum expression of fatty acid synthase (FASN) and an overall greater expression of leptin (LEP); BCS5 was also associated with greater overall adiponectin (ADIPOQ) and peroxisome proliferator-activated receptor gamma (PPARG), whereas overfeeding upregulated expression of proadipogenic miRNA. Higher postpartum expression of chemokine ligand 5 (CCL5) and the cytokines interleukin 6 (IL6) and tumor necrosis factor (TNF) was detected in overfed BCS5 cows. Feed-restricted BCS4 cows had the highest overall interleukin 1 (IL1B) expression. Prepartum feed restriction resulted in greater chemokine ligand 2 (CCL2) expression. Overall, changes in mRNA expression were consistent with the expression pattern of inflammation-related miRNA. These data shed light on molecular mechanisms underlying the effect of prepartum BCS and feeding management on metabolic and inflammatory status of adipose tissue during the peripartum period. Data support the use of a controlled feed restriction prepartum in optimally conditioned cows, as well as the use of a higher level of dietary energy in under-conditioned cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography

PubMed Central

Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-01-01

Objective To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. Methods CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Results Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Conclusions Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients. PMID:23814708

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography.

PubMed

Baysal, Asli; Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-06-01

To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients.

A PARAMETRIC STUDY OF BCS RF SURFACE IMPEDANCE WITH MAGNETIC FIELD USING THE XIAO CODE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reece, Charles E.; Xiao, Binping

2013-09-01

A recent new analysis of field-dependent BCS rf surface impedance based on moving Cooper pairs has been presented.[1] Using this analysis coded in Mathematica TM, survey calculations have been completed which examine the sensitivities of this surface impedance to variation of the BCS material parameters and temperature. The results present a refined description of the "best theoretical" performance available to potential applications with corresponding materials.

Late Intrahepatic Hematoma Complicating Transjugular Intrahepatic Portosystemic Shunt for Budd-Chiari Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terreni, Natalia; Vangeli, Marcello; Raimondo, Maria Luisa

Late intrahepatic hematoma is a rare complication of the transjugular intrahepatic portosystemic shunt (TIPS) procedure. We describe a patient with Budd-Chiari syndrome (BCS), who presented with a large inrahepatic hematoma 13 days after TIPS. Review of the literature reveals only two previous cases, both occurring in patients with BCS and presenting after a similar time interval. This potentially serious complication appears to be specific for TIPS in BCS.

Optimized conditions for MDCK permeability and turbidimetric solubility studies using compounds representative of BCS classes I-IV.

PubMed

Taub, Mitchell E; Kristensen, Lisbeth; Frokjaer, Sven

2002-05-01

The solubility enhancing effects of various excipients, including their compatibility with in vitro permeability (P(app)) systems, was investigated using drugs representative of Biopharmaceutics Classification System (BCS) classes I-IV. Turbidimetric solubility determination using nephelometry and transport experiments using MDCK Strain I cell monolayers were employed. The highest usable concentration of each excipient [dimethyl sulfoxide (DMSO), ethanol, hydroxypropyl-beta-cyclodextrin (HPCD), and sodium taurocholate] was determined by monitoring apical (AP) to basolateral (BL) [14C]mannitol apparent permeability (P(app)) and the transepithelial electrical resistance (TEER) in transport experiments done at pH 6.0 and 7.4. The excipients were used in conjunction with compounds demonstrating relatively low aqueous solubility (amphotericin B, danazol, mefenamic acid, and phenytoin) in order to obtain a drug concentration >50 microM in the donor compartment. The addition of at least one of the selected excipients enhanced the solubility of the inherently poorly soluble compounds to >50 microM as determined via turbidimetric evaluation at pH 6.0 and 7.4. Ethanol and DMSO were found to be generally disruptive to the MDCK monolayer and were not nearly as useful as HPCD and sodium taurocholate. Sodium taurocholate (5 mM) was compatible with MDCK monolayers under all conditions investigated. Additionally, a novel in vitro system aimed at more accurately simulating in vivo conditions, i.e., a pH gradient (6.0 AP/7.4 BL), sodium taurocholate (5 mM, AP), and bovine serum albumin (0.25%, BL), was shown to generate more reliable P(app) values for compounds that are poorly soluble and/or highly protein bound.

Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation.

PubMed

Akiyama, Y; Zicht, R; Ferrone, S; Bonnard, G D; Herberman, R B

1985-04-01

We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti-beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells. As expected, elimination of class II HLA-positive AC with anti-class II HLA MoAb plus complement caused a decrease in proliferation of CTC in response to all the mitogens tested. In contrast, elimination of class II HLA-positive CTC was shown to clearly increase proliferation of CTC, perhaps because this may deplete class II HLA-positive suppressor cells.

Blind Compressed Sensing Enables 3-Dimensional Dynamic Free Breathing Magnetic Resonance Imaging of Lung Volumes and Diaphragm Motion.

PubMed

Bhave, Sampada; Lingala, Sajan Goud; Newell, John D; Nagle, Scott K; Jacob, Mathews

2016-06-01

The objective of this study was to increase the spatial and temporal resolution of dynamic 3-dimensional (3D) magnetic resonance imaging (MRI) of lung volumes and diaphragm motion. To achieve this goal, we evaluate the utility of the proposed blind compressed sensing (BCS) algorithm to recover data from highly undersampled measurements. We evaluated the performance of the BCS scheme to recover dynamic data sets from retrospectively and prospectively undersampled measurements. We also compared its performance against that of view-sharing, the nuclear norm minimization scheme, and the l1 Fourier sparsity regularization scheme. Quantitative experiments were performed on a healthy subject using a fully sampled 2D data set with uniform radial sampling, which was retrospectively undersampled with 16 radial spokes per frame to correspond to an undersampling factor of 8. The images obtained from the 4 reconstruction schemes were compared with the fully sampled data using mean square error and normalized high-frequency error metrics. The schemes were also compared using prospective 3D data acquired on a Siemens 3 T TIM TRIO MRI scanner on 8 healthy subjects during free breathing. Two expert cardiothoracic radiologists (R1 and R2) qualitatively evaluated the reconstructed 3D data sets using a 5-point scale (0-4) on the basis of spatial resolution, temporal resolution, and presence of aliasing artifacts. The BCS scheme gives better reconstructions (mean square error = 0.0232 and normalized high frequency = 0.133) than the other schemes in the 2D retrospective undersampling experiments, producing minimally distorted reconstructions up to an acceleration factor of 8 (16 radial spokes per frame). The prospective 3D experiments show that the BCS scheme provides visually improved reconstructions than the other schemes do. The BCS scheme provides improved qualitative scores over nuclear norm and l1 Fourier sparsity regularization schemes in the temporal blurring and spatial blurring categories. The qualitative scores for aliasing artifacts in the images reconstructed by nuclear norm scheme and BCS scheme are comparable.The comparisons of the tidal volume changes also show that the BCS scheme has less temporal blurring as compared with the nuclear norm minimization scheme and the l1 Fourier sparsity regularization scheme. The minute ventilation estimated by BCS for tidal breathing in supine position (4 L/min) and the measured supine inspiratory capacity (1.5 L) is in good correlation with the literature. The improved performance of BCS can be explained by its ability to efficiently adapt to the data, thus providing a richer representation of the signal. The feasibility of the BCS scheme was demonstrated for dynamic 3D free breathing MRI of lung volumes and diaphragm motion. A temporal resolution of ∼500 milliseconds, spatial resolution of 2.7 × 2.7 × 10 mm, with whole lung coverage (16 slices) was achieved using the BCS scheme.

Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules

PubMed Central

Harton, Jonathan; Jin, Lei; Hahn, Amy; Drake, Jim

2016-01-01

Major histocompatibility complex (MHC) class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naïve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these) to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes) and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II α and β chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail) mediates these “non-traditional” class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease. PMID:27006762

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

PubMed

Li, Wen-Dong; Yu, Hui-Ying; Qian, Ai-Min; Rong, Jian-Jie; Zhang, Ye-Qing; Li, Xiao-Qiang

2017-03-01

To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.

Neural dynamics of motion perception: direction fields, apertures, and resonant grouping.

PubMed

Grossberg, S; Mingolla, E

1993-03-01

A neural network model of global motion segmentation by visual cortex is described. Called the motion boundary contour system (BCS), the model clarifies how ambiguous local movements on a complex moving shape are actively reorganized into a coherent global motion signal. Unlike many previous researchers, we analyze how a coherent motion signal is imparted to all regions of a moving figure, not only to regions at which unambiguous motion signals exist. The model hereby suggests a solution to the global aperture problem. The motion BCS describes how preprocessing of motion signals by a motion oriented contrast (MOC) filter is joined to long-range cooperative grouping mechanisms in a motion cooperative-competitive (MOCC) loop to control phenomena such as motion capture. The motion BCS is computed in parallel with the static BCS of Grossberg and Mingolla (1985a, 1985b, 1987). Homologous properties of the motion BCS and the static BCS, specialized to process motion directions and static orientations, respectively, support a unified explanation of many data about static form perception and motion form perception that have heretofore been unexplained or treated separately. Predictions about microscopic computational differences of the parallel cortical streams V1-->MT and V1-->V2-->MT are made--notably, the magnocellular thick stripe and parvocellular interstripe streams. It is shown how the motion BCS can compute motion directions that may be synthesized from multiple orientations with opposite directions of contrast. Interactions of model simple cells, complex cells, hyper-complex cells, and bipole cells are described, with special emphasis given to new functional roles in direction disambiguation for endstopping at multiple processing stages and to the dynamic interplay of spatially short-range and long-range interactions.

The potential interaction between ewe body condition score and nutrition during very late pregnancy and lactation on the performance of twin-bearing ewes and their lambs

PubMed Central

Cranston, L. M.; Kenyon, P. R.; Corner-Thomas, R. A.; Morris, S. T.

2017-01-01

Objective The present study aimed to determine the impact of ewe body condition score (BCS) (over a range of 2.0 to 3.0) and nutritional treatments (consisting of differing herbage masses) during very late pregnancy and lactation and their potential interaction on the performance of twin-bearing ewes and their lambs to weaning. Methods On day 142 of pregnancy, twin-bearing ewes with a BCS of 2.0, 2.5, or 3.0 were allocated to a “Moderate’ or ‘Unrestricted’ nutritional treatment until day 95 of lactation (weaning). The nutritional treatments aimed to achieve average herbage masses of 1,200 to 1,300 kg dry matter (DM)/ha (Moderate) and 1,500 to 1,800 kg DM/ha (Unrestricted). Results There were no three-way interactions between ewe BCS group, nutritional treatment and time for any ewe or lamb parameter. The nutritional treatments had no effect (p>0.05) on lamb birth or weaning weight. Lambs born to Moderate ewes had greater survival and total litter weight at weaning (p<0.05). Regardless of BCS group, Unrestricted treatment ewes had greater body condition and back-fat depth at weaning than Moderate treatment ewes (p<0.05). Ewes of BCS 2.0 group reared lighter lambs to weaning (p<0.05) and tended to have a lower total litter weight (p = 0.06) than BCS 3.0 group ewes. Conclusion This study suggests farmers should aim to have all ewes with a BCS of 2.5 or 3 in late pregnancy for optimal lamb weaning performance. Furthermore, there is no benefit to lamb production of offering ewes pasture masses >1,200 kg DM/ha during very late pregnancy and lactation. PMID:28231701

The potential interaction between ewe body condition score and nutrition during very late pregnancy and lactation on the performance of twin-bearing ewes and their lambs.

PubMed

Cranston, L M; Kenyon, P R; Corner-Thomas, R A; Morris, S T

2017-09-01

The present study aimed to determine the impact of ewe body condition score (BCS) (over a range of 2.0 to 3.0) and nutritional treatments (consisting of differing herbage masses) during very late pregnancy and lactation and their potential interaction on the performance of twin-bearing ewes and their lambs to weaning. On day 142 of pregnancy, twin-bearing ewes with a BCS of 2.0, 2.5, or 3.0 were allocated to a "Moderate' or 'Unrestricted' nutritional treatment until day 95 of lactation (weaning). The nutritional treatments aimed to achieve average herbage masses of 1,200 to 1,300 kg dry matter (DM)/ha (Moderate) and 1,500 to 1,800 kg DM/ha (Unrestricted). There were no three-way interactions between ewe BCS group, nutritional treatment and time for any ewe or lamb parameter. The nutritional treatments had no effect (p>0.05) on lamb birth or weaning weight. Lambs born to Moderate ewes had greater survival and total litter weight at weaning (p<0.05). Regardless of BCS group, Unrestricted treatment ewes had greater body condition and back-fat depth at weaning than Moderate treatment ewes (p<0.05). Ewes of BCS 2.0 group reared lighter lambs to weaning (p<0.05) and tended to have a lower total litter weight (p = 0.06) than BCS 3.0 group ewes. This study suggests farmers should aim to have all ewes with a BCS of 2.5 or 3 in late pregnancy for optimal lamb weaning performance. Furthermore, there is no benefit to lamb production of offering ewes pasture masses >1,200 kg DM/ha during very late pregnancy and lactation.

Effect of cosmetic outcome on quality of life after breast cancer surgery.

PubMed

Kim, M K; Kim, T; Moon, H G; Jin, U S; Kim, K; Kim, J; Lee, J W; Kim, J; Lee, E; Yoo, T K; Noh, D-Y; Minn, K W; Han, W

2015-03-01

Studies regarding the effects of aesthetic outcomes after breast cancer surgery on quality of life (QoL) have yielded inconsistent results. This study analyzed the aesthetic outcomes and QoL of women who underwent breast conserving surgery (BCS) or total mastectomy with immediate reconstruction (TMIR) using objective and validated methods. QoL questionnaires (EORTC QLQ-C30, BR23, and HADs) were administered at least 1 year after surgery and adjuvant therapy to 485 patients who underwent BCS, 46 who underwent TMIR, and 87 who underwent total mastectomy (TM) without reconstruction. Aesthetic results were evaluated using BCCT.core software and by a panel of physicians. Patients' body image perception was assessed using the body image scale (BIS). QoL outcomes, including for social and role functioning, fatigue, pain, body image, and arm symptoms, were significantly better in the BCS and TMIR groups than in the TM group (p<0.05 each). BIS was significantly better in the BCS than in the TM or TMIR group (p<0.001 each). In the BCS and TMIR groups, general QoL factors were not significantly associated with objective cosmetic outcomes, except for body image in the QLQ-BR23. In contrast, patients with poorer BIS score reported lower QoL in almost all items of the QLQ-C30, BR23, and HADS (p<0.05 each). In conclusion, BCS and TMIR enhanced QoL compared with TM. Among BCS and TMIR patients, objectively measured cosmetic results did not affect general QoL. Self-perception of body image seems to be more important for QoL after breast cancer surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Implementation of national body contouring surgery guidelines following massive weight loss: A national cross-sectional survey of commissioning in England.

PubMed

Dunne, Jonathan A; Wormald, Justin C R; Ghedia, Reshma; Soldin, Mark

2017-01-01

National guidelines for commissioning of body contouring surgery (BCS) following massive weight loss (MWL) in England were published in 2014. Nearly three-quarters of patients who have MWL seek BCS; however, access is known to vary according to the region. The aim of national guidelines was to standardise access. The purpose of this study was to determine implementation of the national guidelines by clinical commissioning groups (CCGs) in England. A cross-sectional, web-based survey was sent to all CCG chairs in England. Of 211 potential respondents, 108 completed the survey or provided funding guidelines (response rate = 52%). Eight CCGs (7%) had implemented the guidelines. A total of 69 CCGs were aware of the new guidelines (64%), and 66 CCGs stated that they fund BCS after MWL (61%). A total of 81 CCGs (75%) identified local funding guidelines, while 15 CCGs (14%) cited individual funding requests (IFRs) as the means of accessing funding. To improve patient access to BCS; 58 of 65 respondents (89%) stated cost-effectiveness, whereas 56 of 75 respondents (75%) thought patient-reported outcome measures were key. Qualitative data to improve access included an integrated pathway from bariatric surgery to BCS, an improved evidence base and greater CCG finances. One CCG stated that it cannot afford to fund cosmetic procedures. The purpose of national guidelines was to simplify the pathway to BCS after MWL and create fair distribution of funds across the country to needy patients; however, their uptake has been poor. Access to funding for BCS across England varies according to the location. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Endogenous minerals have influences on surface electrochemistry and ion exchange properties of biochar.

PubMed

Zhao, Ling; Cao, Xinde; Zheng, Wei; Wang, Qun; Yang, Fan

2015-10-01

The feedstocks for biochar production are diverse and many of them contain various minerals in addition to being rich in carbon. Twelve types of biomass classified into 2 categories: plant-based and municipal waste, were employed to produce biochars under 350 °C and 500 °C. Their pH, point of zero net charge (PZNC), zeta potential, cation and anion exchange capacity (CEC and AEC) were analyzed. The municipal waste-based biochars (MW-BC) had higher mineral levels than the plant-based biochars (PB-BC). However, the water soluble mineral levels were lower in the MW-BCs due to the dominant presence of less soluble minerals, such as CaCO3 and (Ca,Mg)3(PO4)2. The higher total minerals in MW-BCs accounted for the higher PZNC (5.47-9.95) than in PB-BCs (1.91-8.18), though the PZNCs of the PB-BCs increased more than that of the MW-BCs as the production temperature rose. The minerals had influence on the zeta potentials via affecting the negative charges of biochars and the ionic strength of solution. The organic functional groups in PB-BCs such as -COOH and -OH had a greater effect on the CEC and AEC, while the minerals had a greater effect on that of MW-BCs. The measured CEC and AEC values had a strong positive correlation with the total amount of soluble cations and anions, respectively. Results indicated that biochar surface charges depend not only on the organic functional groups, but also on the minerals present and to some extent, minerals have more influences on the surface electrochemistry and ion exchange properties of biochar. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemicals or mutations that target mitochondrial translation can rescue the respiratory deficiency of yeast bcs1 mutants.

PubMed

Panozzo, C; Laleve, A; Tribouillard-Tanvier, D; Ostojić, J; Sellem, C H; Friocourt, G; Bourand-Plantefol, A; Burg, A; Delahodde, A; Blondel, M; Dujardin, G

2017-12-01

Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory deficiency. We have screened chemical libraries and found that two antibiotics, pentamidine and clarithromycin, can compensate two bcs1 point mutations in yeast, one of which is the equivalent of a mutation found in a human patient. As both antibiotics target the large mtrRNA of the mitoribosome, we focused our analysis on mitochondrial translation. We found that the absence of non-essential translation factors Rrf1 or Mif3, which act at the recycling/initiation steps, also compensates for the respiratory deficiency of yeast bcs1 mutations. At compensating concentrations, both antibiotics, as well as the absence of Rrf1, cause an imbalanced synthesis of respiratory subunits which impairs the assembly of the respiratory complexes and especially that of complex IV. Finally, we show that pentamidine also decreases the assembly of complex I in nematode mitochondria. It is well known that complexes III and IV exist within the mitochondrial inner membrane as supramolecular complexes III 2 /IV in yeast or I/III 2 /IV in higher eukaryotes. Therefore, we propose that the changes in mitochondrial translation caused by the drugs or by the absence of translation factors, can compensate for bcs1 mutations by modifying the equilibrium between illegitimate, and thus inactive, and active supercomplexes. Copyright © 2017. Published by Elsevier B.V.

A Sensitivity Study on Modeling Black Carbon in Snow and its Radiative Forcing over the Arctic and Northern China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Yun; Wang, Hailong; Zhang, Rudong

2014-06-02

Black carbon in snow (BCS) simulated in the Community Atmosphere Model (CAM5) is evaluated against measurements over Northern China and the Arctic, and its sensitivity to atmospheric deposition and two parameters that affect post-depositional enrichment is explored. The BCS concentration is overestimated (underestimated) by a factor of two in Northern China (Arctic) in the default model, but agreement with observations is good over both regions in the simulation with improvements in BC transport and deposition. Sensitivity studies indicate that uncertainty in the melt-water scavenging efficiency (MSE) parameter substantially affects BCS and its radiative forcing (by a factor of 2-7) inmore » the Arctic through post-depositional enrichment. The MSE parameter has a relatively small effect on the magnitude of BCS seasonal cycle but can alter its phase in Northern China. The impact of the snow aging scaling factor (SAF) on BCS, partly through the post-depositional enrichment effect, shows more complex latitudinal and seasonal dependence. Similar to MSE, SAF affects more significantly the magnitude (phase) of BCS season cycle over the Arctic (Northern China). While uncertainty associated with the representation of BC transport and deposition processes in CAM5 is more important than that associated with the two snow model parameters in Northern China, the two uncertainties have comparable effect in the Arctic.« less

Sustained attention abnormalities in breast cancer survivors with cognitive deficits post chemotherapy: An electrophysiological study.

PubMed

Kam, J W Y; Brenner, C A; Handy, T C; Boyd, L A; Liu-Ambrose, T; Lim, H J; Hayden, S; Campbell, K L

2016-01-01

Many breast cancer survivors (BCS) report cognitive problems following chemotherapy, yet controversy remains concerning which cognitive domains are affected. This study investigated a domain crucial to daily function: the ability to maintain attention over time. We examined whether BCS who self-reported cognitive problems up to 3 years following cancer treatment (n=19) performed differently from healthy controls (HC, n=12) in a task that required sustained attention. Participants performed a target detection task while periodically being asked to report their attentional state. Electroencephalogram was recorded during this task and at rest. BCS were less likely to maintain sustained attention during the task compared to HC. Further, the P3 event-related potential component elicited by visual targets during the task was smaller in BCS relative to HC. BCS also displayed greater neural activity at rest. BCS demonstrated an abnormal pattern of sustained attention and resource allocation compared to HC, suggesting that attentional deficits can be objectively observed in breast cancer survivors who self-report concentration problems. These data underscore the value of EEG combined with a less traditional measure of sustained attention, or attentional states, as objective laboratory tools that are sensitive to subjective complaints of chemotherapy-related attentional impairments. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Evaluation of the membrane permeability (PAMPA and skin) of benzimidazoles with potential cannabinoid activity and their relation with the Biopharmaceutics Classification System (BCS).

PubMed

Alvarez-Figueroa, M Javiera; Pessoa-Mahana, C David; Palavecino-González, M Elisa; Mella-Raipán, Jaime; Espinosa-Bustos, Cristián; Lagos-Muñoz, Manuel E

2011-06-01

The permeability of five benzimidazole derivates with potential cannabinoid activity was determined in two models of membranes, parallel artificial membrane permeability assay (PAMPA) and skin, in order to study the relationship of the physicochemical properties of the molecules and characteristics of the membranes with the permeability defined by the Biopharmaceutics Classification System. It was established that the PAMPA intestinal absorption method is a good predictor for classifying these molecules as very permeable, independent of their thermodynamic solubility, if and only if these have a Log P(oct) value <3.0. In contrast, transdermal permeability is conditioned on the solubility of the molecule so that it can only serve as a model for classifying the permeability of molecules that possess high solubility (class I: high solubility, high permeability; class III: high solubility, low permeability).

25 CFR 522.5 - Disapproval of a class II ordinance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Disapproval of a class II ordinance. 522.5 Section 522.5 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.5 Disapproval of a class II...

Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates

PubMed Central

2013-01-01

Background Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The non-classical class II DM molecule, HLA-DM in the case of humans, possesses critical function in assisting the classical MHC class II molecules for proper peptide loading and is highly conserved in tetrapod species. Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not. To obtain a clear answer, we comprehensively searched class II genes in representative teleost fish genomes and analyzed those genes regarding the critical functional features required for the DM system. Results We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE). Based on several criteria, we investigated the classical/non-classical nature of various class II genes and showed that only one of three groups (DA) exhibits classical-type characteristics. Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish. Conclusions Teleost fish, a major group of vertebrates, do not possess the DM system for the classical class II peptide-loading and this sophisticated system has specially evolved in the tetrapod lineage. PMID:24279922

Superfluid density of states and pseudogap phenomenon in the BCS-BEC crossover regime of a superfluid Fermi gas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Ryota; Tsuchiya, Shunji; CREST

2010-10-15

We investigate single-particle excitations and strong-coupling effects in the BCS-BEC crossover regime of a superfluid Fermi gas. Including phase and amplitude fluctuations of the superfluid order parameter within a T-matrix theory, we calculate the superfluid density of states (DOS), as well as single-particle spectral weight, over the entire BCS-BEC crossover region below the superfluid transition temperature T{sub c}. We clarify how the pseudogap in the normal state evolves into the superfluid gap, as one passes through T{sub c}. While the pseudogap in DOS continuously evolves into the superfluid gap in the weak-coupling BCS regime, the superfluid gap in the crossovermore » region is shown to appear in DOS after the pseudogap disappears below T{sub c}. In the phase diagram with respect to the temperature and interaction strength, we determine the region where strong pairing fluctuations dominate over single-particle properties of the system. Our results would be useful for the study of strong-coupling phenomena in the BCS-BEC crossover regime of a superfluid Fermi gas.« less

The Landscape of Somatic Genetic Alterations in Breast Cancers From ATM Germline Mutation Carriers.

PubMed

Weigelt, Britta; Bi, Rui; Kumar, Rahul; Blecua, Pedro; Mandelker, Diana L; Geyer, Felipe C; Pareja, Fresia; James, Paul A; Couch, Fergus J; Eccles, Diana M; Blows, Fiona; Pharoah, Paul; Li, Anqi; Selenica, Pier; Lim, Raymond S; Jayakumaran, Gowtham; Waddell, Nic; Shen, Ronglai; Norton, Larry; Wen, Hannah Y; Powell, Simon N; Riaz, Nadeem; Robson, Mark E; Reis-Filho, Jorge S; Chenevix-Trench, Georgia

2018-02-28

Pathogenic germline variants in ataxia-telangiectasia mutated (ATM), a gene that plays a role in DNA damage response and cell cycle checkpoints, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic characteristics and landscape of somatic genetic alterations in 24 BCs from ATM germline mutation carriers by whole-exome and targeted sequencing. ATM-associated BCs were consistently hormone receptor positive and largely displayed minimal immune infiltrate. Although 79.2% of these tumors exhibited loss of heterozygosity of the ATM wild-type allele, none displayed high activity of mutational signature 3 associated with defective homologous recombination DNA (HRD) repair. No TP53 mutations were found in the ATM-associated BCs. Analysis of an independent data set confirmed that germline ATM variants and TP53 somatic mutations are mutually exclusive. Our findings indicate that ATM-associated BCs often harbor bi-allelic inactivation of ATM, are phenotypically distinct from BRCA1/2-associated BCs, lack HRD-related mutational signatures, and that TP53 and ATM genetic alterations are likely epistatic.

Quenching characteristics of bathocuproinedisulfonic acid, disodium salt in aqueous solution and copper sulfate plating solution

NASA Astrophysics Data System (ADS)

Koga, Toshiaki; Hirakawa, Chieko; Takeshita, Michinori; Terasaki, Nao

2018-04-01

Bathocuproinedisulfonic acid, disodium salt (BCS) is generally used to detect Cu(I) through a color reaction. We newly found BCS fluorescence in the visible blue region in an aqueous solution. However, the fluorescence mechanism of BCS is not well known, so we should investigate its fundamental information. We confirmed that the characteristics of fluorescence are highly dependent on the molecular concentration and solvent properties. In particular, owing to the presence of the copper compound, the fluorescence intensity extremely decreases. By fluorescence quenching, we observed that a copper compound concentration of 10-6 mol/L or less could easily be measured in an aqueous solution. We also observed BCS fluorescence in copper sulfate plating solution and the possibility of detecting monovalent copper by fluorescence reabsorption.

A visual system for scoring body condition of Asian elephants (Elephas maximus).

PubMed

Wijeyamohan, Shanmugasundaram; Treiber, Kibby; Schmitt, Dennis; Santiapillai, Charles

2015-01-01

A body condition score (BCS) may provide information on the health or production potential of an animal; it may also reflect the suitability of the environment to maintain an animal population. Thus assessing the BCS of Asian elephants is important for their management. There is a need for a robust BCS applicable to both wild and captive elephants of all age categories based on the minimum and maximum possible subcutaneous body fat and muscle deposits. The visually based system for scoring the body condition of elephants presented here satisfies these criteria and is quick, inexpensive, non-invasive and user-friendly in the field. The BCS scale correlates (P < 0.05) with morphometric indices such as weight, girth, and skin fold measures. © 2014 Wiley Periodicals, Inc.

Application of fecal near-infrared spectroscopy and nutritional balance software to monitor diet quality and body condition in beef cows grazing Arizona rangeland.

PubMed

Tolleson, D R; Schafer, D W

2014-01-01

Monitoring the nutritional status of range cows is difficult. Near-infrared spectroscopy (NIRS) of feces has been used to predict diet quality in cattle. When fecal NIRS is coupled with decision support software such as the Nutritional Balance Analyzer (NUTBAL PRO), nutritional status and animal performance can be monitored. Approximately 120 Hereford and 90 CGC composite (50% Red Angus, 25% Tarentaise, and 25% Charolais) cows grazing in a single herd were used in a study to determine the ability of fecal NIRS and NutbalPro to project BCS (1 = thin and 9 = fat) under commercial scale rangeland conditions in central Arizona. Cattle were rotated across the 31,000 ha allotment at 10 to 20 d intervals. Cattle BCS and fecal samples (approximately 500 g) composited from 5 to 10 cows were collected in the pasture approximately monthly at the midpoint of each grazing period. Samples were frozen and later analyzed by NIRS for prediction of diet crude protein (CP) and digestible organic matter (DOM). Along with fecal NIRS predicted diet quality, animal breed type, reproductive status, and environmental conditions were input to the software for each fecal sampling and BCS date. Three different evaluations were performed. First, fecal NIRS and NutbalPro derived BCS was projected forward from each sampling as if it were a "one-time only" measurement. Second, BCS was derived from the average predicted weight change between 2 sampling dates for a given period. Third, inputs to the model were adjusted to better represent local animals and conditions. Fecal NIRS predicted diet quality varied from a minimum of approximately 5% CP and 57% DOM in winter to a maximum of approximately 11% CP and 60% DOM in summer. Diet quality correlated with observed seasonal changes and precipitation events. In evaluation 1, differences in observed versus projected BCS were not different (P > 0.1) between breed types but these values ranged from 0.1 to 1.1 BCS in Herefords and 0.0 to 0.9 in CGC. In evaluation 2, differences in observed versus projected BCS were not different (P > 0.1) between breed types but these values ranged from 0.00 to 0.46 in Hereford and 0.00 to 0.67 in CGC. In evaluation 3, the range of differences between observed and projected BCS was 0.04 to 0.28. The greatest difference in projected versus observed BCS occurred during periods of lowest diet quality. Body condition was predicted accurately enough to be useful in monitoring the nutrition of range beef cows under the conditions of this study.

Long-Term Follow-Up After Successful Transjugular Intrahepatic Portosystemic Shunt Placement in a Pediatric Patient with Budd-Chiari Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco Cesar, E-mail: fcarnevale@uol.com.br; Szejnfeld, Denis, E-mail: denis@cura.com.br; Moreira, Airton Mota

Orthotopic liver transplantation is the standard of care in patients with Budd-Chiari syndrome (BCS), and transjugular intrahepatic portosystemic shunt (TIPS) has become an important adjunct procedure while the patient is waiting for a liver. No long-term follow up of TIPS in BCS patients has been published in children. We report successful 10-year follow-up of a child with BCS and iatrogenic TIPS dysfunction caused by oral contraceptive use.

The overlooked "nonclassical" functions of major histocompatibility complex (MHC) class II antigens in immune and nonimmune cells.

PubMed

Altomonte, M; Pucillo, C; Maio, M

1999-06-01

Besides their "classical" antigenic peptide-presenting activity, major histocompatibility complex (MHC) class II antigens can activate different cellular functions in immune and nonimmune cells. However, this "nonclassical" role and its functional consequences are still substantially overlooked. In this review, we will focus on these alternative functional properties of MHC class II antigens, to reawaken attention to their present and foreseeable immunobiologic and pathogenetic implications. The main issues that will be addressed concern 1) the role of MHC class II molecules as basic components of exchangeable oligomeric protein complexes with intracellular signaling ability; 2) the nonclassical functions of MHC class II antigens in immune cells; 3) the pathogenetic role of MHC class II antigens in inflammatory/autoimmune and infectious disease; and 4) the functional role of MHC class II antigens in solid malignancies.

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Sloan, M A; Alexandrov, A V; Tegeler, C H; Spencer, M P; Caplan, L R; Feldmann, E; Wechsler, L R; Newell, D W; Gomez, C R; Babikian, V L; Lefkowitz, D; Goldman, R S; Armon, C; Hsu, C Y; Goodin, D S

2004-05-11

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.8 What are the minimum technical software standards applicable to Class II... of Class II games. (a) Player interface displays. (1) If not otherwise provided to the player, the player interface shall display the following: (i) The purchase or wager amount; (ii) Game results; and...

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.8 What are the minimum technical software standards applicable to Class II... of Class II games. (a) Player interface displays. (1) If not otherwise provided to the player, the player interface shall display the following: (i) The purchase or wager amount; (ii) Game results; and...

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.8 What are the minimum technical software standards applicable to Class II... of Class II games. (a) Player interface displays. (1) If not otherwise provided to the player, the player interface shall display the following: (i) The purchase or wager amount; (ii) Game results; and...

Genetic analysis of efficiency traits in Austrian dairy cattle and their relationships with body condition score and lameness.

PubMed

Köck, A; Ledinek, M; Gruber, L; Steininger, F; Fuerst-Waltl, B; Egger-Danner, C

2018-01-01

This study is part of a larger project whose overall objective was to evaluate the possibilities for genetic improvement of efficiency in Austrian dairy cattle. In 2014, a 1-yr data collection was carried out. Data from 6,519 cows kept on 161 farms were recorded. In addition to routinely recorded data (e.g., milk yield, fertility, disease data), data of novel traits [e.g., body weight (BW), body condition score (BCS), lameness score, body measurements] and individual feeding information and feed quality were recorded on each test-day. The specific objective of this study was to estimate genetic parameters for efficiency (related) traits and to investigate their relationships with BCS and lameness in Austrian Fleckvieh, Brown Swiss, and Holstein cows. The following efficiency (related) traits were considered: energy-corrected milk (ECM), BW, dry matter intake (DMI), energy intake (INEL), ratio of milk output to metabolic BW (ECM/BW 0.75 ), ratio of milk output to DMI (ECM/DMI), and ratio of milk energy output to total energy intake (LE/INEL, LE = energy in milk). For Fleckvieh, the heritability estimates of the efficiency (related) traits ranged from 0.11 for LE/INEL to 0.44 for BW. Heritabilities for BCS and lameness were 0.19 and 0.07, respectively. Repeatabilities were high and ranged from 0.30 for LE/INEL to 0.83 for BW. Heritability estimates were generally lower for Brown Swiss and Holstein, but repeatabilities were in the same range as for Fleckvieh. In all 3 breeds, more-efficient cows were found to have a higher milk yield, lower BW, slightly higher DMI, and lower BCS. Higher efficiency was associated with slightly fewer lameness problems, most likely due to the lower BW (especially in Fleckvieh) and higher DMI of the more-efficient cows. Body weight and BCS were positively correlated. Therefore, when selecting for a lower BW, BCS is required as additional information because, otherwise, no distinction between large animals with low BCS and smaller animals with normal BCS would be possible. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effect of mare obesity and endocrine function on foal birthweight in Thoroughbreds.

PubMed

Smith, S; Marr, C M; Dunnett, C; Menzies-Gow, N J

2017-07-01

Birthweight of Thoroughbred foals has increased in recent years. It is unknown whether this is associated with increased broodmare obesity or endocrine dysfunction. To determine insulin, leptin and triglyceride concentrations in Thoroughbred mares throughout gestation and investigate their association with obesity and foal birthweight. Cohort study. A total of 66 mares were included from 40 days post-breeding. Body condition score (BCS), weight and blood samples were obtained every 60 days throughout gestation. Serum/plasma insulin, leptin and triglyceride concentrations and foal birthweight were recorded. Associations between hormone/triglyceride concentration with BCS, stage of gestation and birthweight were analysed using a linear mixed effects model. Serum insulin concentrations were greater at 1-60 days (4.31 μiu/mL) compared with 241-300 days (3.13 μiu/mL) and 61-120 days (5.33 μiu/mL) compared with 181-240, 241-300 and 301-360 days (3.78, 3.13, 3.37 μiu/mL) gestation (P<0.05). There was no significant hyperinsulinaemia and no association of insulin concentration with BCS. Leptin concentration was greater at 181-240 days (2.28 μg/L, P<0.0001) compared with all other time points and correlated with BCS (P<0.0003). Triglyceride concentration was greater at 241-300 days (0.245 mmol, P<0.02) compared with earlier time points, but was not associated with BCS. Foal birthweight was weakly positively correlated with BCS (r = 0.13, P<0.001) and inversely correlated with leptin concentrations at 61-120 and 241-300 days gestation (r = -0.64, P<0.05). Reduction in sample size over the study and tight clustering of BCS. Mare BCS correlated with foal birthweight; obese mares had heavier foals. Significant hyperinsulinaemia was not identified in this population. Increased leptin concentration in early and late gestation was associated with decreased foal birthweight. Further work is required to establish whether leptin concentration in late gestation could predict foal birthweight. © 2016 EVJ Ltd.

A 27-Year Experience With Surgical Treatment of Budd-Chiari Syndrome

PubMed Central

Orloff, Marshall J.; Daily, Pat O.; Orloff, Susan L.; Girard, Barbara; Orloff, Mark S.

2000-01-01

Objective To determine the effects of surgical portal decompression in Budd-Chiari syndrome (BCS) on survival, quality of life, shunt patency, liver function, portal hemodynamics, and hepatic morphology during periods ranging from 3.5 to 27 years. Summary Background Data Experiments in the authors’ laboratory showed that surgical portal decompression reversed the deleterious effects of BCS on the liver. This study was aimed at determining whether similar benefit could be obtained in patients with BCS. Methods From 1972 to 1999, the authors conducted prospective studies of the treatment of 60 patients with BCS who were divided into three groups: the first had occlusion confined to the hepatic veins treated by direct side-to-side portacaval shunt (SSPCS); the second had occlusion involving the inferior vena cava (IVC) treated by a portal decompressive procedure that bypassed the obstructed IVC; and the third group, who had advanced cirrhosis and hepatic decompensation and were referred too late for treatment by portal decompression, required orthotopic liver transplantation. Results In the 32 patients with BCS resulting from hepatic vein occlusion alone, SSPCS had a surgical death rate of 3%, and 94% of the patients were alive 3.5 to 27 years after surgery. All 31 survivors remained free of ascites and almost all had normal liver function. No patient with a patent shunt had encephalopathy. The SSPCS remained patent in all but one patient. Liver biopsies showed no evidence of congestion or necrosis, and 48% of the biopsies were diagnosed as normal. Mesoatrial shunt was performed in eight patients with BCS caused by IVC thrombosis. All patients survived surgery, but five subsequently developed thrombosis of the synthetic graft and died. Because of the poor results, mesoatrial shunt was abandoned. Instead, a high-flow combination shunt was introduced, consisting of SSPCS combined with a cavoatrial shunt (CAS) through a Gore-Tex graft. There were no surgical or long-term deaths among 10 patients who underwent combined SSPCS and CAS, and the shunts functioned effectively during 4 to 16 years of follow-up. Ten patients with advanced cirrhosis were referred too late to benefit from surgical portal decompression, and they were approved and listed for orthotopic liver transplantation. Three patients died of liver failure while awaiting a transplant, and four patients died after the transplant. The 1- and 5-year survival rates were 40% and 30%, respectively. Conclusions SSPCS in BCS with hepatic vein occlusion alone results in reversal of liver damage, correction of hemodynamic disturbances, prolonged survival, and good quality of life when performed early in the course of BCS. Similarly good results are obtained with combined SSPCS and CAS in patients with BCS resulting from IVC occlusion. In contrast, mesoatrial shunt has been discontinued in the authors’ program because of an unacceptable incidence of graft thrombosis and death. In patients with advanced cirrhosis from long-standing, untreated BCS, orthotopic liver transplantation is the only hope of relief and results in the salvage of some patients. The key to long survival in BCS is prompt diagnosis and treatment by portal decompression. PMID:10973384

Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice.

PubMed

Liu, Z Q; Wu, Y; Song, J P; Liu, X; Liu, Z; Zheng, P Y; Yang, P C

2013-10-01

B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet. This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice. The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs. A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice. CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantum fluctuations in the BCS-BEC crossover of two-dimensional Fermi gases

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Lianyi; Lu, Haifeng; Cao, Gaoqing

2015-08-14

We present a theoretical study of the ground state of the BCS-BEC crossover in dilute two-dimensional Fermi gases. While the mean-field theory provides a simple and analytical equation of state, the pressure is equal to that of a noninteracting Fermi gas in the entire BCS-BEC crossover, which is not consistent with the features of a weakly interacting Bose condensate in the BEC limit and a weakly interacting Fermi liquid in the BCS limit. The inadequacy of the two-dimensional mean-field theory indicates that the quantum fluctuations are much more pronounced than those in three dimensions. In this work, we show thatmore » the inclusion of the Gaussian quantum fluctuations naturally recovers the above features in both the BEC and the BCS limits. In the BEC limit, the missing logarithmic dependence on the boson chemical potential is recovered by the quantum fluctuations. Near the quantum phase transition from the vacuum to the BEC phase, we compare our equation of state with the known grand canonical equation of state of two-dimensional Bose gases and determine the ratio of the composite boson scattering length a B to the fermion scattering length a 2D. We find a B ≃ 0.56a 2D, in good agreement with the exact four-body calculation. As a result, we compare our equation of state in the BCS-BEC crossover with recent results from the quantum Monte Carlo simulations and the experimental measurements and find good agreements.« less

Short communication: Genetic relationships of milk coagulation properties with body condition score and linear type traits in Holstein-Friesian cows.

PubMed

Cassandro, M; Battagin, M; Penasa, M; De Marchi, M

2015-01-01

Milk coagulation properties (MCP) are gaining popularity among dairy cattle producers and the improvement of traits associated with MCP is expected to result in a benefit for the dairy industry, especially in countries with a long tradition in cheese production. The objectives of this study were to estimate genetic correlations of MCP with body condition score (BCS) and type traits using data from first-parity Italian Holstein-Friesian cattle. The data analyzed consisted of 18,460 MCP records from 4,036 cows with information on both BCS and conformation traits. The cows were daughters of 246 sires and the pedigree file included a total of 37,559 animals. Genetic relationships of MCP with BCS and type traits were estimated using bivariate animal models. The model for MCP included fixed effects of stage of lactation, and random effects of herd-test-date, cow permanent environment, additive genetic animal, and residual. Fixed factors considered in the model for BCS and type traits were herd-date of evaluation and interaction between age at scoring and stage of lactation of the cow, and random terms were additive genetic animal, cow permanent environment, and residual. Genetic relationships between MCP and BCS, and MCP and type traits were generally low and significant only in a few cases, suggesting that MCP can be selected for without detrimental effects on BCS and linear type traits. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Developing a post-treatment survivorship care plan to help breast cancer survivors understand their fertility.

PubMed

Gorman, Jessica R; Julian, Anne K; Roberts, Samantha A; Romero, Sally A D; Ehren, Jennifer L; Krychman, Michael L; Boles, Sarah G; Mao, Jun; Irene Su, H

2018-02-01

Reproductive-aged breast cancer survivors (BCS) who have completed initial cancer treatment frequently want to know about their future fertility potential. The purpose of this qualitative study was to assess if the fertility-related content presented in the survivorship care plan prototype met the informational needs of post-treatment BCS and to provide an opportunity for the target audience to review and react to the proposed content and design. We conducted and analyzed transcripts from seven focus groups with BCS to evaluate their reactions to the survivorship care plan prototype. We independently coded transcripts for consistent themes and sub-themes and used a consensus-building approach to agree on interpretation of results. We identified five themes that describe the post-treatment BCS' responses to the prototype survivorship care plan in the context of their informational needs and experiences: (1) the prototype's fertility-related information is relevant; (2) desire for clinical parameters to help survivors understand their infertility risk; (3) fertility-related information is important throughout survivorship; (4) evidence-based content from a neutral source is trustworthy; and (5) the recommendation to see a fertility specialist is helpful, but cost is a barrier. BCS have concerns and needs related to their fertility potential after initial breast cancer treatment. The evidence-based information offered in our prototype survivorship care plan was acceptable to BCS and has significant potential to address these needs. Additional primary data that identify post-cancer treatment indicators of fertility would advance this effort.

Genetic relationships among body condition score, body weight, milk yield, and fertility in dairy cows.

PubMed

Berry, D P; Buckley, F; Dillon, P; Evans, R D; Rath, M; Veerkamp, R F

2003-06-01

Genetic (co)variances between body condition score (BCS), body weight (BW), milk production, and fertility-related traits were estimated. The data analyzed included 8591 multiparous Holstein-Friesian cows with records for BCS, BW, milk production, and/or fertility from 78 seasonal calving grass-based farms throughout southern Ireland. Of the cows included in the analysis, 4402 had repeated records across the 2 yr of the study. Genetic correlations between level of BCS at different stages of lactation and total lactation milk production were negative (-0.51 to -0.14). Genetic correlations between BW at different stages of lactation and total lactation milk production were all close to zero but became positive (0.01 to 0.39) after adjusting BW for differences in BCS. Body condition score at different stages of lactation correlated favorably with improved fertility; genetic correlations between BCS and pregnant 63 d after the start of breeding season ranged from 0.29 to 0.42. Both BW at different stages of lactation and milk production tended to exhibit negative genetic correlations with pregnant to first service and pregnant 63 d after the start of the breeding season and positive genetic correlations with number of services and the interval from first service to conception. Selection indexes investigated illustrate the possibility of continued selection for increased milk production without any deleterious effects on fertility or average BCS, albeit, genetic merit for milk production would increase at a slower rate.

Spatial distribution of potentially bioavailable metals in surface soils of a contaminated sports ground in Galway, Ireland.

PubMed

Dao, Ligang; Morrison, Liam; Kiely, Ger; Zhang, Chaosheng

2013-04-01

Assessing the environmental risk of metal contamination in soils requires the determination of both total (TCs) and bioavailable (BCs) element concentrations. A total of 200 surface (0-10 cm) soil samples were collected from an urban sports ground (South Park) in Galway, Ireland, a former landfill and dumping site, which is currently under remediation. The potential BCs of metals were measured using ethylene-diamine-tetra-acetic acid (EDTA) extraction followed by inductively coupled plasma-optical emission spectrometry analysis, while the TCs were determined using portable X-ray fluorescence spectrometry. It was found that Zn was primarily present in the insoluble residue (EDTA un-extractable) fraction in soils, with the median ratio of BCs/TCs 0.27. However, Pb and Cu had higher ratios of BCs/TCs (median values of 0.60 and 0.39, respectively) suggesting that they are potentially more bioavailable in the soils. The spatial distribution maps showed that both TCs and BCs for Cu, Pb and Zn in the study area were spatially heterogeneous. It was found that the BCs exhibited generally similar spatial patterns as their TCs of Cu, Pb and Zn: high values were mainly located in the west, north-east and south-east portions of the study area, where only a thin layer of topsoil existed. It was recommended that the current remediation action for this site needs to be carried out on an urgent basis.

Coamorphous Loratadine-Citric Acid System with Enhanced Physical Stability and Bioavailability.

PubMed

Wang, Jin; Chang, Ruimiao; Zhao, Yanan; Zhang, Jiye; Zhang, Ting; Fu, Qiang; Chang, Chun; Zeng, Aiguo

2017-10-01

Coamorphous systems using citric acid as a small molecular excipient were studied for improving physical stability and bioavailability of loratadine, a BCS class II drug with low water solubility and high permeability. Coamorphous loratadine-citric acid systems were prepared by solvent evaporation technique and characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy. Solid-state analysis proofed that coamorphous loratadine-citric acid system (1:1) was amorphous and homogeneous, had a higher T g over amorphous loratadine, and the intermolecular hydrogen bond interactions between loratadine and citric acid exist. The solubility and dissolution of coamorphous loratadine-citric acid system (1:1) were found to be significantly greater than those of crystalline and amorphous form. The pharmacokinetic study in rats proved that coamorphous loratadine-citric acid system (1:1) could significantly improve absorption and bioavailability of loratadine. Coamorphous loratadine-citric acid system (1:1) showed excellently physical stability over a period of 3 months at 25°C under 0% RH and 25°C under 60% RH conditions. The improved stability of coamorphous loratadine-citric acid system (1:1) could be related to an elevated T g over amorphous form and the intermolecular hydrogen bond interactions between loratadine and citric acid. These studies demonstrate that the developed coamorphous loratadine-citric acid system might be a promising oral formulation for improving solubility and bioavailability of loratadine.

Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs.

PubMed

De Smet, Lieselotte; Saerens, Lien; De Beer, Thomas; Carleer, Robert; Adriaensens, Peter; Van Bocxlaer, Jan; Vervaet, Chris; Remon, Jean Paul

2014-05-01

The aim of the study is to increase the bioavailability of itraconazole (ITRA) using nanosized cocrystals prepared via wet milling of ITRA in combination with dicarboxylic acids. Wet milling was used in order to create a nanosuspension of ITRA in combination with dicarboxylic acids. After spray-drying and bead layering, solid state was characterized by MDSC, XRD, Raman and FT-IR. The release profiles and bioavailability of the nanococrystalline suspension, the spray-dried and bead layered formulation were evaluated. A monodisperse nanosuspension (549±51nm) of ITRA was developed using adipic acid and Tween®80. Solid state characterization indicated the formation of nanococrystals by hydrogen bounds between the triazole group of ITRA and the carboxyl group of adipic acid. A bioavailability study was performed in dogs. The faster drug release from the nanocrystal-based formulation was reflected in the in vivo results since Tmax of the formulations was obtained 3h after administration, while Tmax of the reference formulation was observed only 6h after administration. This fast release of ITRA was obtained by a dual concept: manufacturing of nanosized cocrystals of ITRA and adipic acid via wet milling. Formation of stable nanosized cocrystals via this approach seems a good alternative for amorphous systems to increase the solubility and obtain a fast drug release of BCS class II drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

PubMed

Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

2015-09-01

Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Rapidly absorbed orodispersible tablet containing molecularly dispersed felodipine for management of hypertensive crisis: development, optimization and in vitro/in vivo studies.

PubMed

Basalious, Emad B; El-Sebaie, Wessam; El-Gazayerly, Omaima

2013-01-01

A liquisolid orodispersible tablet of felodipine, a BCS Class II drug, was developed to improve drug dissolution and absorption through the buccal mucosa for management of hypertensive crisis. A 24 full-factorial design was applied to optimize felodipine liquisolid systems (FLSs) having acceptable flow properties and possessing enhanced drug dissolution rates. Four formulation variables; The liquid type, X1 (PG or PEG), drug concentration, X2 (10% and 20%), type of coat, X3 (Aerosil® and Aeroperl®) and excipients ratio, X4 (10 and 20) were included in the design. The systems were assessed for dissolution and flow properties. Following optimization, the formulation components (X1, X2, X3 and X4) were PEG, 10%, Aerosil® and 20, respectively. The optimized FLS was compressed into felodipine liquisolid orodispersible tablet using Prosolv® as carrier material (FLODT-2). The in vitro and in vivo disintegration times of FLODT-2 were 9 and 7 s, respectively. The in vivo pharmacokinetic study using human volunteers showed a significant increase in dissolution and absorption rates of the formulation of FLODT-2 compared to soft gelatin capsules filled with felodipine solution in PEG under the same conditions. Our results proposed that the optimized FLODT formulation could be promising to manage hypertensive crisis.

40 CFR 147.3200 - Fort Peck Indian Reservation: Assiniboine & Sioux Tribes-Class II wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: Assiniboine & Sioux Tribes-Class II wells. 147.3200 Section 147.3200 Protection of Environment ENVIRONMENTAL... INJECTION CONTROL PROGRAMS Assiniboine and Sioux Tribes § 147.3200 Fort Peck Indian Reservation: Assiniboine & Sioux Tribes—Class II wells. The UIC program for Class II injection wells on all lands within the...

40 CFR 147.3200 - Fort Peck Indian Reservation: Assiniboine & Sioux Tribes-Class II wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: Assiniboine & Sioux Tribes-Class II wells. 147.3200 Section 147.3200 Protection of Environment ENVIRONMENTAL... INJECTION CONTROL PROGRAMS Assiniboine and Sioux Tribes § 147.3200 Fort Peck Indian Reservation: Assiniboine & Sioux Tribes—Class II wells. The UIC program for Class II injection wells on all lands within the...

40 CFR 147.3200 - Fort Peck Indian Reservation: Assiniboine & Sioux Tribes-Class II wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: Assiniboine & Sioux Tribes-Class II wells. 147.3200 Section 147.3200 Protection of Environment ENVIRONMENTAL... INJECTION CONTROL PROGRAMS Assiniboine and Sioux Tribes § 147.3200 Fort Peck Indian Reservation: Assiniboine & Sioux Tribes—Class II wells. The UIC program for Class II injection wells on all lands within the...

78 FR 24061 - Minimum Technical Standards for Class II Gaming Systems and Equipment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Register that established technical standards for ensuring the integrity of electronic Class II games and aids. 73 FR 60508, Oct. 10, 2008. The technical standards were designed to assist tribal gaming... Class II gaming systems. The standards did not classify which games were Class II games and which games...

40 CFR 147.3400 - Navajo Indian lands-Class II wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Navajo Indian lands-Class II wells... Indian Lands § 147.3400 Navajo Indian lands—Class II wells. The UIC program for Class II injection wells... outside those exterior boundaries (collectively referred to as “Navajo Indian lands for which EPA has...

77 FR 37058 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

...] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance... availability of the draft guidance entitled ``Class II Special Controls Guidance Document: Implanted Blood... blood access devices may comply with the requirement of special controls for class II devices. This...

Differential Transmembrane Domain GXXXG Motif Pairing Impacts Major Histocompatibility Complex (MHC) Class II Structure*

PubMed Central

Dixon, Ann M.; Drake, Lisa; Hughes, Kelly T.; Sargent, Elizabeth; Hunt, Danielle; Harton, Jonathan A.; Drake, James R.

2014-01-01

Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II αβ heterodimer in determining molecular structure and function. Our previous studies identified an MHC class II conformer that is marked by the Ia.2 epitope. These Ia.2+ class II conformers are lipid raft-associated and able to drive both tyrosine kinase signaling and efficient antigen presentation to CD4 T cells. Here, we establish that the Ia.2+ I-Ak conformer is formed early in the class II biosynthetic pathway and that differential pairing of highly conserved transmembrane domain GXXXG dimerization motifs is responsible for formation of Ia.2+ versus Ia.2− I-Ak class II conformers and controlling lipid raft partitioning. These findings provide a molecular explanation for the formation of two distinct MHC class II conformers that differ in their inherent ability to signal and drive robust T cell activation, providing new insight into the role of MHC class II in regulating antigen-presenting cell-T cell interactions critical to the initiation and control of multiple aspects of the immune response. PMID:24619409

40 CFR 144.19 - Transitioning from Class II to Class VI.

Code of Federal Regulations, 2011 CFR

2011-07-01

... primary purpose of long-term storage into an oil and gas reservoir must apply for and obtain a Class VI geologic sequestration permit when there is an increased risk to USDWs compared to Class II operations. In... Class II operations and a Class VI permit is required. In order to make this determination the Director...

International genetic evaluation of Holstein bulls for overall type traits and body condition score.

PubMed

Battagin, M; Forabosco, F; Jakobsen, J H; Penasa, M; Lawlor, T J; Cassandro, M

2012-08-01

The study documents the procedures used to estimate genetic correlations among countries for overall conformation (OCS), overall udder (OUS), overall feet and legs (OFL), and body condition score (BCS) of Holstein sires. Major differences in traits definition are discussed, in addition to the use of international breeding values (IBV) among countries involved in international genetic evaluations, and similarities among countries through hierarchical clustering. Data were available for populations from 20 countries for OCS and OUS, 18 populations for OFL, and 11 populations for BCS. The IBV for overall traits and BCS were calculated using a multi-trait across-country evaluation model. Distance measures, obtained from genetic correlations, were used as input values in the cluster analysis. Results from surveys sent to countries participating in international genetic evaluation for conformation traits showed that different ways of defining traits are used: the overall traits were either computed from linear or composite traits or defined as general characteristics. For BCS, populations were divided into 2 groups: one scored and evaluated BCS, and one used a best predictor. In general, populations were well connected except for Estonia and French Red Holstein. The average number of common bulls for the overall traits ranged from 19 (OCS and OUS of French Red Holstein) to 514 (OFL of United States), and for BCS from 17 (French Red Holstein) to 413 (the Netherlands). The average genetic correlation (range) across countries was 0.75 (0.35 to 0.95), 0.80 (0.41 to 0.95), and 0.68 (0.12 to 0.89) for OCS, OUS, and OFL, respectively. Genetic correlations among countries that used angularity as best predictor for BCS and countries that scored BCS were negative. The cluster analysis provided a clear picture of the countries distances; differences were due to trait definition, trait composition, and weights in overall traits, genetic ties, and genotype by environment interactions. Harmonization of trait definition and increasing genetic ties could improve genetic correlations across countries and reduce the distances. In each national selection index, all countries, except Estonia and New Zealand, included at least one overall trait, whereas none included BCS. Out of 18 countries, 9 have started genomic evaluation of conformation traits. The first were Canada, France, New Zealand, and United States in 2009, followed by Switzerland, Germany, and the Netherlands in 2010, and Australia and Denmark-Finland-Sweden (joint evaluation) in 2011. Six countries are planning to start soon. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A Triad of Molecular Regions Contribute to the Formation of Two Distinct MHC Class II Conformers

PubMed Central

Drake, Lisa A.; Drake, James R.

2016-01-01

MHC class II molecules present antigen-derived peptides to CD4 T cells to drive the adaptive immune response. Previous work has established that class II αβ dimers can adopt two distinct conformations, driven by the differential pairing of transmembrane domain GxxxG dimerization motifs. These class II conformers differ in their ability to be loaded with antigen-derived peptide and to effectively engage CD4 T cells. Motif 1 (M1) paired I-Ak class II molecules are efficiently loaded with peptides derived from the processing of B cell receptor-bound antigen, have unique B cell signaling properties and high T cell stimulation activity. The 11-5.2 mAb selectively binds M1 paired I-Ak class II molecules. However, the molecular determinants of 11-5.2 binding are currently unclear. Here, we report the ability of a human class II transmembrane domain to drive both M1 and M2 class II conformer formation. Protease sensitivity analysis further strengthens the idea that there are conformational differences between the extracellular domains of M1 and M2 paired class II. Finally, MHC class II chain alignments and site directed mutagenesis reveals a triad of molecular regions that contributes to 11-5.2 mAb binding. In addition to transmembrane GxxxG motif domain pairing, 11-5.2 binding is influenced directly by α chain residue Glu-71 and indirectly by the region around the inter-chain salt bridge formed by α chain Arg-52 and β chain Glu-86. These findings provide insight into the complexity of 11-5.2 mAb recognition of the M1 paired I-Ak class II conformer and further highlight the molecular heterogeneity of peptide-MHC class II complexes that drive T cell antigen recognition. PMID:27148821

Maxillary and mandibular contribution to the establishment of class II malocclusion in an adult Lebanese population.

PubMed

El Hajj, Nadine; Bassil-Nassif, Nayla; Tauk, Alain; Mouhanna-Fattal, Carole; Bouserhal, Joseph P

2017-12-01

The main aim of this study was to describe the contribution of the maxilla and the mandible to the establishment of a Class II skeletal malocclusion in an adult Lebanese population. Secondary aims were to detect the presence of sex-based dimorphism and to study the influence of the vertical dimension on the Class II skeletal pattern. A sample of 90 adults in skeletal Class II was recruited and equally distributed according to sex and vertical typology. The study describes the skeletal and dentoalveolar cephalometric characteristics of the Class II sample, essentially according to Coben's cephalometric analysis. The total effective depth of the cranial base and the anterior cranial base angle (SN-BaH) were both greater in the Class II sample. In females, the effective depth of the maxilla (Ptm-A) was larger than normal while SNB was smaller. The parameters describing the size and shape of the body of the mandible were significantly different from those of normal subjects. The upper incisors were in a retrusive position, while the axis of the lower incisors was located normally. The mandibular molars had a more distal sagittal position. Hyperdivergent subjects had more significant posterior alveolar growth, a more retrusive mandibular position and smaller mandibular dimensions than the other two vertical sub-groups. The cranial base contributes to the establishment of a Class II malocclusion, and mandibular retrusion cannot be considered as a characteristic shared by all skeletal Class II subjects. Lessening of the absolute length of the mandibular body is the second most frequent etiological factor noted in the Class II sample studied. Most individuals in skeletal Class II have an associated dental Class II malocclusion, and the vertical dimension has an influence on the Class II skeletal pattern. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanoma.

PubMed

Dankner, Matthew; Lajoie, Mathieu; Moldoveanu, Dan; Nguyen, Tan-Trieu; Savage, Paul; Rajkumar, Shivshankari; Huang, Xiu; Lvova, Maria; Protopopov, Alexei; Vuzman, Dana; Hogg, David; Park, Morag; Guiot, Marie-Christine; Petrecca, Kevin; Mihalcioiu, Catalin; Watson, Ian R; Siegel, Peter M; Rose, April A N

2018-06-14

Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi. Tumors from patients with BRAF WT, V600E (class I) and L597S (class II) metastatic melanoma were used to generate patient-derived-xenografts (PDX). We assembled a panel of melanoma cell lines with class IIa (activation segment) or IIb (p-loop) mutations and compared these to wild-type or V600E/K BRAF mutant cells. Cell lines and PDXs were treated with BRAFi (vemurafenib, dabrafenib, encorafenib, LY3009120), MEKi (cobimetinib, trametinib, binimetinib) or the combination. We identified two patients with BRAF L597S metastatic melanoma who were treated with dMAPKi. BRAFi impaired MAPK signalling and cell growth in class I and II BRAF mutant cells. dMAPKi was more effective than either single MAPKi at inhibiting cell growth in all class II BRAF mutant cells tested. dMAPKi caused tumor regression in two melanoma PDXs with class II BRAF mutations, and prolonged survival of mice with class II BRAF mutant melanoma brain metastases. Two patients with BRAF L597S mutant melanoma clinically responded to dMAPKi. Class II BRAF mutant melanoma are growth inhibited by dMAPKi. Responses to dMAPKi have been observed in two patients with class II BRAF mutant melanoma. This data provides rationale for clinical investigation of dMAPKi in patients with class II BRAF mutant metastatic melanoma. Copyright ©2018, American Association for Cancer Research.

Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro

PubMed Central

2014-01-01

Introduction The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n = 10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured through P8; cells from each passage (P2 to P8) were cryopreserved until used. Immunophenotyping of MHC class I and II, CD44, CD29, CD90, LFA-1, and CD45RB was performed by using flow cytometry. Tri-lineage differentiation assays were performed to confirm MSC multipotency. Recombinant equine IFN-γ was used to stimulate MHC class II negative MSCs in culture, after which expression of MHC class II was re-examined. To assess the ability of MHC class II negative or positive MSCs to stimulate an immune response, modified one-way mixed leukocyte reactions (MLRs) were performed by using MHC-matched and mismatched responder PBLs and stimulator PBLs or MSCs. Proliferation of gated CFSE-labeled CD3+ responder T cells was evaluated via CFSE attenuation by using flow cytometry and reported as the number of cells in the proliferating T-cell gate. Results MSCs varied widely in MHC class II expression despite being homogenous in terms of “stemness” marker expression and ability to undergo trilineage differentiation. Stimulation of MHC class II negative MSCs with IFN-γ resulted in markedly increased expression of MHC class II. MLR results revealed that MHC-mismatched MHC class II-positive MSCs caused significantly increased responder T-cell proliferation compared with MHC-mismatched MHC class II-negative and MHC-matched MSCs, and equivalent to that of the positive control of MHC-mismatched leukocytes. Conclusions The results of this study suggest that MSCs should be confirmed as MHC class II negative before allogeneic application. Additionally, it must be considered that even MHC class II-negative MSCs could upregulate MHC class II expression if implanted into an area of active inflammation, as demonstrated with in vitro stimulation with IFN-γ. PMID:24461709

Twisting Anderson pseudospins with light: Quench dynamics in THz-pumped BCS superconductors

NASA Astrophysics Data System (ADS)

Chou, Yang-Zhi; Liao, Yunxiang; Foster, Matthew

We study the preparation and the detection of coherent far-from-equilibrium BCS superconductor dynamics in THz pump-probe experiments. In a recent experiment, an intense monocycle THz pulse with center frequency ω = Δ was injected into a superconductor with BCS gap Δ the post-pump evolution was detected via the optical conductivity. It was argued that nonlinear coupling of the pump to the Anderson pseudospins of the superconductor induces coherent dynamics of the Higgs mode Δ (t) . We validate this picture in a 2D BCS model with a combination of exact numerics and the Lax reduction, and we compute the dynamical phase diagram. The main effect of the pump is to scramble the orientations of Anderson pseudospins along the Fermi surface by twisting them in the xy-plane. We show that more intense pulses can induce a far-from-equilibrium gapless phase (phase I), originally predicted in the context of interaction quenches. We show that the THz pump can reach phase I at much lower energy densities than an interaction quench, and we demonstrate that Lax reduction provides a quantitative tool for computing coherent BCS dynamics. We also compute the optical conductivity for the states discussed here.

Synthesis, structural and semiconducting properties of Ba(Cu1/3 Sb2/3)O3-PbTiO3 solid solutions

NASA Astrophysics Data System (ADS)

Singh, Chandra Bhal; Kumar, Dinesh; Prashant, Verma, Narendra Kumar; Singh, Akhilesh Kumar

2018-05-01

We report the synthesis and properties of a new solid solution 0.05Ba(Cu1/3Sb2/3)O3-0.95PbTiO3 (BCS-PT) which shows the semiconducting properties. In this study, we have designed new perovskite-type (ABO3) solid solution of BCS-PT that have tunable optical band gap. BCS-PT compounds were prepared by conventional solid-state reaction method and their structural, micro-structural and optical properties were analyzed. The calcination temperature for BCS-PT solid solutions has been optimized to obtain a phase pure system. The Reitveld analysis of X-ray data show that all samples crystallize in tetragonal crystal structure with space group P4mm. X-ray investigation revealed that increase in calcination temperature led to increase of lattice parameter `a' while `c' parameter value lowered. The band gap of PbTiO3 is reduced from 3.2 eV to 2.8 eV with BCS doping and with increasing calcination temperature it further reduces to 2.56 eV. The reduced band gap indicated that the compounds are semiconducting and can be used for photovoltaic device applications.

A new approach on JPSS VIIRS BCS and SVS PRT calibration

NASA Astrophysics Data System (ADS)

Wang, Tung R.; Marschke, Steve; Borroto, Michael; Jones, Christopher M.; Chovit, Christopher

2015-05-01

A set of calibrated platinum resistance thermometers (PRT's) was used to monitor the temperature of a Blackbody Calibration Source (BCS) and Space View Source (SVS). BCS is Ground Support Equipment (GSE) used to validate the emissive band calibration of Visible Infrared Imaging Radiometer Suite (VIIRS) of the Joint Polar Satellite System (JPSS). Another GSE, the SVS was used as an optical simulator to provide zero radiance sources for all VIIRS bands. The required PRT temperature 1 uncertainty is less than 0.030K. A process was developed to calibrate the PRTs in its thermal block by selecting a single thermal bath fluid that is compatible with spaceflight, is easy to clean and supported the entire temperature range. The process involves thermal cycling the PRTs that are installed in an aluminum housing using RTV566A prior to calibration. The PRTs were calibrated thermal cycled again and then calibrated once more to verify repeatability. Once completed these PRTs were installed on both the BCS and SVS. The PRT calibration uncertainty was estimated and deemed sufficient to support the effective temperature requirements for the operating temperature range of the BCS and SVS.

Addressing Factors Associated with Arab Women's Socioeconomic Status May Reduce Breast Cancer Mortality: Report from a Well Resourced Middle Eastern Country.

PubMed

Donnelly, Tam Truong; Al Khater, Al-Hareth; Al Kuwari, Mohamed Ghaith; Al-Bader, Salha Bujassoum; Abdulmalik, Mariam; Al-Meer, Nabila; Singh, Rajvir; Fung, Tak

2015-01-01

Differences in socioeconomic status (SES) such as income levels may partly explain why breast cancer screening (BCS) disparities exist in countries where health care services are free or heavily subsidized. However, factors that contribute to such differences in SES among women living in well resourced Middle East countries are not fully understood. This quantitative study investigated factors that influence SES and BCS of Arab women. Understanding of such factors can be useful for the development of effective intervention strategies that aim to increase BCS uptake among Arab women. Using data from a cross-sectional survey among 1,063 Arabic-speaking women in Qatar, age 35+, additional data analysis was performed to determine the relationship between socioeconomic indicators such as income and other factors in relation to BCS activities. This study found that income is determined and influenced by education level, occupation, nationality, years of residence in the country, level of social activity, self-perceived health status, and living area. Financial stress, unemployment, and unfavorable social conditions may impede women's participation in BCS activities in well resourced Middle East countries.

G.L. Amidon, H. Lennernas, V.P. Shah, and J.R. Crison. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995--backstory of BCS.

PubMed

Shah, Vinod P; Amidon, Gordon L

2014-09-01

The Biopharmaceutics Classification System (BCS) has become widely accepted today in the academic, industrial, and regulatory world. While the initial application of the BCS was to regulatory science bioequivalence (BE) issues and related implications, it has come to be utilized widely by the pharmaceutical industry in drug discovery and development as well. This brief manuscript will relate the story of the BCS development. While much of the ground work for the BCS goes back to the pharmacokinetic and drug absorption research by Gordon Amidon (GLA) in the 1970s and 1980s, the realization of the need for a classification or categorization of drug and drug products for setting dissolution standards became apparent to GLA during his 1990-1991 sabbatical year at the FDA. Initiated at the invitation of the then CEDR director, Dr. Carl Peck, to become a visiting scientist at the FDA, the goal was to promote regulatory research at the FDA, in my case, in biopharmaceutics, and to develop a science-based system to simplify regulatory requirements.

The BCS-BEC Crossover

NASA Astrophysics Data System (ADS)

Parish, Meera M.

2015-09-01

This chapter presents the crossover from the Bardeen-Cooper-Schrieffer (BCS) state of weakly correlated pairs of fermions to the Bose-Einstein condensation (BEC) of diatomic molecules in the atomic Fermi gas. Our aim is to provide a pedagogical review of the BCS-BEC crossover, with an emphasis on the basic concepts, particularly those that are not generally known or are difficult to find in the literature. We shall not attempt to give an exhaustive survey of current research in the limited space here; where possible, we will direct the reader to more extensive reviews.

Two-neutron decay within RMF+BCS approach

NASA Astrophysics Data System (ADS)

Kumawat, M.; Singh, U. K.; Saxena, G.; Kaushik, M.; Jain, S. K.

2018-05-01

A theoretical global study has been done for identifying possible candidates of 2n-radioactivity for all even and odd nuclei under proton number Z ≤ 40 by employing Relativistic Mean-Filed plus BCS (RMF+BCS) approach. We investigate two-and one-neutron separation energy, deformation, pairing energy, wave-function, potential and other ground state properties for our study of even and odd Z nuclei to find candidates of 2n-decay within Z ≤ 40. These results are found in agreement of recent experiments and consistent with other parameters of RMF and other theories.

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

Influence of melatonin receptor 1A gene polymorphisms on seasonal reproduction in Sarda ewes with different body condition scores and ages.

PubMed

Mura, M C; Luridiana, S; Bodano, S; Daga, C; Cosso, G; Diaz, M L; Bini, P P; Carcangiu, V

2014-10-01

In several species, circadian changes in melatonin concentrations play a key role in the photoperiodic control of seasonality. In sheep, two silent mutations in the melatonin receptor 1A gene (MTNR1A) at positions 606 and 612 of the exon II are associated with seasonal reproduction. However, in some sheep breeds, no relationships have been found between MTNR1A polymorphisms and reproductive seasonality. This lack of relationship could be due to effects of breed, body condition, age, and/or environmental conditions. Thus, the present study was conducted with the Sarda sheep breed with the aim of documenting the effect of MTNR1A gene polymorphisms on reproductive resumption and to evaluate whether such this effect was modified by differences in body condition score (BCS) and age. Six hundred three- to six-year-old multiparous ewes with BCSs between 2.5 and 3.5 were selected. Genomic DNA was extracted and subjected to PCR to amplify the ovine exon II of the MTNR1A gene. The amplicons were subjected to digestion with the restriction enzymes RsaI and MnlI to detect the T606C and A612G polymorphisms, respectively. Ewes carrying the G/G, G/A, C/C, and C/T genotypes exhibited higher fertility rates (P<0.05) and fewer numbers of days between the introduction of rams and parturition (P<0.05) than did the A/A and T/T genotypes. The data revealed that the MTNR1A gene polymorphisms influenced spring reproductive resumption in the Sarda sheep breed. Moreover, the data also indicated that, over the limited ranges evaluated in this study, BCS and age had no significant influence on reproductive activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs.

PubMed

Borba, Paola Aline Amarante; Pinotti, Marihá; de Campos, Carlos Eduardo Maduro; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2016-02-10

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45 min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30 min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis(®), however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis(®) are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Relationship between serum adiponectin concentration, body condition score, and peripheral tissue insulin response of dairy cows during the dry period.

PubMed

De Koster, J; Urh, C; Hostens, M; Van den Broeck, W; Sauerwein, H; Opsomer, G

2017-04-01

The aim of the present study was to describe the relationship between serum adiponectin concentration and peripheral tissue insulin response in dairy cows with a variable body condition score (BCS) during the dry period. Cows were selected at the beginning of the dry period based on BCS (BCS <3.75, n = 4; BCS >3.75, n = 5). Animals were followed from the beginning of the dry period by weekly blood sampling and assessment of BCS and backfat thickness. Weekly blood samples were analyzed for adiponectin concentration using a bovine specific ELISA. Hyperinsulinemic euglycemic clamp tests were performed at the end of the dry period to measure peripheral tissue insulin response. Insulin dose response curves were established for both glucose and fatty acid metabolism. Regression analysis revealed that the serum concentrations of adiponectin dropped at the end of the dry period (P < 0.05) and were negatively associated with BCS (P < 0.05). At the level of the glucose metabolism, serum concentrations of adiponectin were positively correlated with insulin responsiveness (reflecting the maximal effect of insulin; r = 0.76, P < 0.05), but not with insulin sensitivity (reflecting the insulin concentration needed to achieve halfmaximal effect; r = -0.54, P = 0.13). At the level of the fatty acid metabolism, greater adiponectin concentrations were negatively correlated with lower NEFA levels during the HEC test reflecting the insulin responsiveness of the NEFA metabolism (r = -0.61, P = 0.08), whereas there was no association with the insulin sensitivity of the NEFA metabolism (r = -0.16, P = 0.67). In conclusion, serum concentrations of adiponectin were negatively associated with the BCS of dairy cows during the dry period and positively associated with insulin responsiveness of the glucose and fatty acid metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a Body Condition Scoring Index for Female African Elephants Validated by Ultrasound Measurements of Subcutaneous Fat

PubMed Central

Morfeld, Kari A.; Lehnhardt, John; Alligood, Christina; Bolling, Jeff; Brown, Janine L.

2014-01-01

Obesity-related health and reproductive problems may be contributing to non-sustainability of zoo African elephant (Loxodonta africana) populations. However, a major constraint in screening for obesity in elephants is lack of a practical method to accurately assess body fat. Body condition scoring (BCS) is the assessment of subcutaneous fat stores based on visual evaluation and provides an immediate appraisal of the degree of obesity of an individual. The objective of this study was to develop a visual BCS index for female African elephants and validate it using ultrasound measures of subcutaneous fat. To develop the index, standardized photographs were collected from zoo (n = 50) and free-ranging (n = 57) female African elephants for identifying key body regions and skeletal features, which were then used to visually determine body fat deposition patterns. This information was used to develop a visual BCS method consisting of a list of body regions and the physical criteria for assigning an overall score on a 5-point scale, with 1 representing the lowest and 5 representing the highest levels of body fat. Results showed that as BCS increased, ultrasound measures of subcutaneous fat thickness also increased (P<0.01), indicating the scores closely coincide with physical measures of fat reserves. The BCS index proved to be reliable and repeatable based on high intra- and inter-assessor agreement across three assessors. In comparing photographs of wild vs. captive African elephants, the median BCS in the free-ranging individuals (BCS = 3, range 1–5) was lower (P<0.001) than that of the zoo population (BCS = 4, range 2–5). In sum, we have developed the first validated BCS index for African elephants. This tool can be used to examine which factors impact body condition in zoo and free-ranging elephants, providing valuable information on how it affects health and reproductive potential of individual elephants. PMID:24718304

Development of a body condition scoring index for female African elephants validated by ultrasound measurements of subcutaneous fat.

PubMed

Morfeld, Kari A; Lehnhardt, John; Alligood, Christina; Bolling, Jeff; Brown, Janine L

2014-01-01

Obesity-related health and reproductive problems may be contributing to non-sustainability of zoo African elephant (Loxodonta africana) populations. However, a major constraint in screening for obesity in elephants is lack of a practical method to accurately assess body fat. Body condition scoring (BCS) is the assessment of subcutaneous fat stores based on visual evaluation and provides an immediate appraisal of the degree of obesity of an individual. The objective of this study was to develop a visual BCS index for female African elephants and validate it using ultrasound measures of subcutaneous fat. To develop the index, standardized photographs were collected from zoo (n = 50) and free-ranging (n = 57) female African elephants for identifying key body regions and skeletal features, which were then used to visually determine body fat deposition patterns. This information was used to develop a visual BCS method consisting of a list of body regions and the physical criteria for assigning an overall score on a 5-point scale, with 1 representing the lowest and 5 representing the highest levels of body fat. Results showed that as BCS increased, ultrasound measures of subcutaneous fat thickness also increased (P<0.01), indicating the scores closely coincide with physical measures of fat reserves. The BCS index proved to be reliable and repeatable based on high intra- and inter-assessor agreement across three assessors. In comparing photographs of wild vs. captive African elephants, the median BCS in the free-ranging individuals (BCS = 3, range 1-5) was lower (P<0.001) than that of the zoo population (BCS = 4, range 2-5). In sum, we have developed the first validated BCS index for African elephants. This tool can be used to examine which factors impact body condition in zoo and free-ranging elephants, providing valuable information on how it affects health and reproductive potential of individual elephants.

The effect of nutrition and body condition of triplet-bearing ewes during late pregnancy on the behaviour of ewes and lambs.

PubMed

Gronqvist, Gabriella V; Corner-Thomas, Rene A; Kenyon, Paul R; Stafford, Kevin J; Morris, Stephen T; Hickson, Rebecca Edith

2018-04-12

Triplet-born lambs are less likely to survive to weaning than twin-born or single-born lambs. Appropriate ewe-lamb bonding behaviours and lamb vigour behaviours are necessary for survival of lambs. The aim of this experiment was to determine whether maternal nutrition during late pregnancy influenced behaviour of the ewe and her lambs soon after birth, and to determine whether mid-pregnancy body condition score (BCS) influenced any behavioural response. The experiments included ewes that were in BCS 2.0, 2.5 or 3.0 in mid-pregnancy and were fed either ad libitum or to pregnancy-maintenance requirements in late-pregnancy (day 115 until 136 in experiment one, and day 128 until 141 in experiment two). The time taken for lambs to stand, contact dam, suck from dam and follow dam was recorded three to 18 hours after birth. The number of high- and low-pitched bleats emitted by the ewe and lambs was recorded, along with maternal behaviour score (MBS) of the ewe. Lambs in experiment two underwent a maternal-recognition test at 12 or 24 h. There were significant effects of feeding treatment on bleating behaviour of ewes and lambs, but these were inconsistent among BCS groups and between experiments. Lamb vigour behaviours were not affected by feeding treatment. In experiment one, there was no effect of feeding treatment or BCS on MBS, but in experiment two, ewes in BCS3 in mid-pregnancy had greater MBS than ewes in BCS2 in mid-pregnancy (MBS 3.1/5 vs MBS 2.1/5; P<0.05). Given there were no repeatable effects on behaviour of ewes and lambs, ad libitum feeding rather than feeding for pregnancy-maintenance requirements can not be used to improve behaviours soon after birth of triplet-bearing ewes in BCS 2 - 3 and their lambs in extensive pastoral conditions.

Bcs1p can rescue a large and productive cytochrome bc(1) complex assembly intermediate in the inner membrane of yeast mitochondria.

PubMed

Conte, Laura; Trumpower, Bernard L; Zara, Vincenzo

2011-01-01

The yeast cytochrome bc(1) complex, a component of the mitochondrial respiratory chain, is composed of ten distinct protein subunits. In the assembly of the bc(1) complex, some ancillary proteins, such as the chaperone Bcs1p, are actively involved. The deletion of the nuclear gene encoding this chaperone caused the arrest of the bc(1) assembly and the formation of a functionally inactive bc(1) core structure of about 500-kDa. This immature bc(1) core structure could represent, on the one hand, a true assembly intermediate or, on the other hand, a degradation product and/or an incorrect product of assembly. The experiments here reported show that the gradual expression of Bcs1p in the yeast strain lacking this protein was progressively able to rescue the bc(1) core structure leading to the formation of the functional homodimeric bc(1) complex. Following Bcs1p expression, the mature bc(1) complex was also progressively converted into two supercomplexes with the cytochrome c oxidase complex. The capability of restoring the bc(1) complex and the supercomplexes was also possessed by the mutated yeast R81C Bcsp1. Notably, in the human ortholog BCS1L, the corresponding point mutation (R45C) was instead the cause of a severe bc(1) complex deficiency. Differently from the yeast R81C Bcs1p, two other mutated Bcs1p's (K192P and F401I) were unable to recover the bc(1) core structure in yeast. This study identifies for the first time a productive assembly intermediate of the yeast bc(1) complex and gives new insights into the molecular mechanisms involved in the last steps of bc(1) assembly. Copyright © 2010 Elsevier B.V. All rights reserved.

Prenatal maternal effects on body condition score, female fertility, and milk yield of dairy cows.

PubMed

Banos, G; Brotherstone, S; Coffey, M P

2007-07-01

In this study, maternal effects were described as age of dam at first and second calving, first-lactation body condition score (BCS) of the dam during gestation, and milk yield of the dam. The impact of these effects on first-lactation daughter BCS, fertility, and test-day milk yield was assessed. The effect of milk yield of dam on daughter 305-d yield in the latter's first 3 lactations was also investigated. The proportion of total phenotypic variance in daughter traits accounted for by maternal effects was calculated. Dams calving early for the first time (18 to 23 mo of age) had daughters that produced 4.5% more first-lactation daily milk, had 7% higher BCS, and had their first service 3 d earlier than cows whose dams calved late (30 to 36 mo). However, daughters of dams that calved early had difficulties conceiving as they needed 7% more inseminations and had a 7.5% higher return rate. Cows from second calvings of relatively young (36 to 41 mo) dams produced 6% more first-lactation daily milk, had 2% higher BCS, and showed a significantly better fertility profile than cows whose dams calved at a late age (47 to 55 mo). High maternal BCS during gestation had a favorable effect on daughter BCS, nonreturn rate, and number of inseminations per conception. However, it was also associated with a small decrease in daughter daily milk yield. Changes in dam BCS during gestation did not affect daughter performance significantly. Maternal effects of milk yield of the dam, expressed as her permanent environment during lactation, adversely affected daughter 305-d milk, fat, and protein yield. However, although the effect was significant, it was practically negligible (<0.3% of the mean). Finally, overall maternal effects accounted for a significant proportion of the total phenotypic variance of calving interval (1.4 +/- 0.6%) and nonreturn rate (1.1 +/- 0.5%).

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

Postoperative surgical complications of lymphadenohysterocolpectomy

PubMed Central

Marin, F; Pleşca, M; Bordea, CI; Voinea, SC; Burlănescu, I; Ichim, E; Jianu, CG; Nicolăescu, RR; Teodosie, MP; Maher, K; Blidaru, A

2014-01-01

Rationale The current standard surgical treatment for the cervix and uterine cancer is the radical hysterectomy (lymphadenohysterocolpectomy). This has the risk of intraoperative accidents and postoperative associated morbidity. Objective The purpose of this article is the evaluation and quantification of the associated complications in comparison to the postoperative morbidity which resulted after different types of radical hysterectomy. Methods and results Patients were divided according to the type of surgery performed as follows: for cervical cancer – group A- 37 classic radical hysterectomies Class III Piver - Rutledge -Smith ( PRS ), group B -208 modified radical hysterectomies Class II PRS and for uterine cancer- group C -79 extended hysterectomies with pelvic lymphadenectomy from which 17 patients with paraaortic lymphnode biopsy . All patients performed preoperative radiotherapy and 88 of them associated radiosensitization. Discussion Early complications were intra-abdominal bleeding ( 2.7% Class III PRS vs 0.48% Class II PRS), supra-aponeurotic hematoma ( 5.4% III vs 2.4% II) , dynamic ileus (2.7% III vs 0.96% II) and uro - genital fistulas (5.4% III vs 0.96% II).The late complications were the bladder dysfunction (21.6% III vs 16.35% II) , lower limb lymphedema (13.5% III vs 11.5% II), urethral strictures (10.8% III vs 4.8% II) , incisional hernias ( 8.1% III vs 7.2% II), persistent pelvic pain (18.91% III vs 7.7% II), bowel obstruction (5.4% III vs 1.4% II) and deterioration of sexual function (83.3% III vs 53.8% II). PRS class II radical hysterectomy is associated with fewer complications than PRS class III radical hysterectomy , except for the complications of lymphadenectomy . A new method that might reduce these complications is a selective lymphadenectomy represented by sentinel node biopsy . In conclusion PRS class II radical hysterectomy associated with neoadjuvant radiotherapy is a therapeutic option for the incipient stages of cervical cancer. Abbreviations: PRS- Piver Rutledge-Smith, II- class II, III- class III PMID:24653760

Tuning across the BCS-BEC crossover in superconducting Fe1+ySexTe1-x : An angle-resolved photoemission study

NASA Astrophysics Data System (ADS)

Rinott, Shahar; Ribak, Amit; Chashka, Khanan; Randeria, Mohit; Kanigel, Amit

The crossover from Bardeen-Cooper-Schrieffer (BCS) superconductivity to Bose-Einstein condensation (BEC) was never realized in quantum materials. It is difficult to realize because, unlike in ultra cold atoms, one cannot tune the pairing interaction. We realize the BCS-BEC crossover in a nearly compensated semimetal Fe1+ySexTe1-x by tuning the Fermi energy ɛF via chemical doping, which permits us to systematically change Δ /ɛF from 0 . 16 to 0 . 50 , where Δ is the superconducting (SC) gap. We use angle-resolved photoemission spectroscopy to measure the Fermi energy, the SC gap and characteristic changes in the SC state electronic dispersion as the system evolves from a BCS to a BEC regime. Our results raise important questions about the crossover in multi-band superconductors which go beyond those addressed in the context of cold atoms.

Effect of Education Based on Health Belief Model on the Behavior of Breast Cancer Screening in Women.

PubMed

Masoudiyekta, Leila; Rezaei-Bayatiyani, Hojat; Dashtbozorgi, Bahman; Gheibizadeh, Mahin; Malehi, Amal Saki; Moradi, Mehrnaz

2018-01-01

The purpose of this study was to determine the effect of education based on health belief model (HBM) on the behavior of breast cancer screening (bCS) in women. This quasi-experimental study was conducted on 226 women who were selected with cluster sampling method from those referred to Dezful health centers. Data collection tool was a researcher-made questionnaire. Demographic questionnaire bCS- scale, and the Knowledge about questionnaire, all given before and 3 months after the intervention. According to the findings of the study, there was a significant relationship between women's performance and variables of knowledge, perceived sensitivity, perceived benefits, perceived barriers, self-efficacy, and cues to action. Poor knowledge of women indicates a crucial need for formal educational programs to sensitize women regarding the importance of bCS. These educational programs should consider factors affecting bCS behaviors.

Auger electron spectroscopy and x-ray photoelectron spectroscopy of the biocorrosion of copper by Gum Arabic, BCS and Pseudomonas atlantica exopolymer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jolley, J.G.; Geesey, G.G.; Hankins, M.R.

1987-01-01

Thin films (3.4 nm) of copper on germanium substrates were exposed to 10% Gum Arabic aqueous solution, 1% BCS (aqueous and simulated sea water solutions) and 0.5% Pseudomonas atlantica exopolymer (aqueous and simulated sea water solutions). Pre- and post-exposure characterization were done by Auger electron spectroscopy and x-ray photoelectron spectroscopy. Ancillary graphite furnace atomic absorption spectroscopy was used to monitor the removal process of the copper thin film from the germanium substrate. Results indicate that the copper was oxidized by the Gum Arabic and BCS, and some was removed from the Cu/Ge interface by all three polymers and incorporated intomore » the polymer matrix. Thus biocorrosion of copper was exhibited by the Gum Arabic, BCS and Pseudomonas atlantica exopolymer. 14 refs., 4 figs., 3 tabs.« less

BEC-BCS crossover and the liquid-gas phase transition in hot and dense nuclear matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin Meng; Urban, Michael; Schuck, Peter

2010-08-15

The effect of nucleon-nucleon correlations in symmetric nuclear matter at finite temperature is studied beyond BCS theory. Starting from a Hartree-Fock description of nuclear matter with the Gogny effective interaction, we add correlations corresponding to the formation of preformed pairs and scattering states above the superfluid critical temperature within the in-medium T-matrix approach, which is analogous to the Nozieres-Schmitt-Rink theory. We calculate the critical temperature for a BEC superfluid of deuterons, of a BCS superfluid of nucleons, and in the crossover between these limits. The effect of the correlations on thermodynamic properties (equation of state, energy, entropy) and the liquid-gasmore » phase transition is discussed. Our results show that nucleon-nucleon correlations beyond BCS play an important role for the properties of nuclear matter, especially in the low-density region.« less

Specific heat and effects of strong pairing fluctuations in a superfluid Fermi atom gas in the BCS-BEC crossover region

NASA Astrophysics Data System (ADS)

van Wyk, Pieter; Inotani, Daisuke; Ohashi, Yoji

2018-03-01

We theoretically investigate the specific heat at constant volume C V in the BCS(Bardeen-Cooper-Schrieffer)-BEC(Bose-Einstein-condensation)-crossover regime of an ultracold Fermi gas, below the superfluid phase transition temperature T c. Within the strong-coupling framework developed by Nozières and Schmitt-Rink, we show that the temperature dependence of C V drastically changes as one passes through the crossover region, and is sensitive to strong fluctuations in the Cooper channel near the unitarity limit. We also compare our results to a recent experiment on a 6Li unitary Fermi gas. Since fluctuation effects are a crucial key in the BCS-BEC-crossover phenomenon, our results would be helpful in considering how the fermionic BCS superfluid changes into BEC with increasing the interaction strength, from the viewpoint of specific heat.

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

Major histocompatibility complex class II molecule expression on muscle cells is regulated by differentiation: implications for the immunopathogenesis of muscle autoimmune diseases.

PubMed

Mantegazza, R; Gebbia, M; Mora, M; Barresi, R; Bernasconi, P; Baggi, F; Cornelio, F

1996-08-01

Major histocompatibility complex (MHC) class II molecules are expressed on myoblasts after interferon-gamma (IFN-gamma) treatment, suggesting a muscle cell involvement in antigen presentation in inflammatory myopathies. However, they were not observed on normal or pathological myofibers. This discrepancy might be related to different responsiveness of developmentally differentiated muscle cells to IFN-gamma. Myoblasts expressed class II transcripts and proteins after IFN-gamma, while myotubes and innervated contracting muscle cells did not show staining for class II molecules. At all cell stages no loss of IFN-gamma receptor was detected indicating that myofiber maturation blocks their capacity to express MHC class II molecules. This suggests that completely differentiated myofibers cannot participate in class II restricted immunological reactions.

Twisting Anderson pseudospins with light: Quench dynamics in terahertz-pumped BCS superconductors

NASA Astrophysics Data System (ADS)

Chou, Yang-Zhi; Liao, Yunxiang; Foster, Matthew S.

2017-03-01

We study the preparation (pump) and the detection (probe) of far-from-equilibrium BCS superconductor dynamics in THz pump-probe experiments. In a recent experiment [R. Matsunaga, Y. I. Hamada, K. Makise, Y. Uzawa, H. Terai, Z. Wang, and R. Shimano, Phys. Rev. Lett. 111, 057002 (2013), 10.1103/PhysRevLett.111.057002], an intense monocycle THz pulse with center frequency ω ≃Δ was injected into a superconductor with BCS gap Δ ; the subsequent postpump evolution was detected via the optical conductivity. It was argued that nonlinear coupling of the pump to the Anderson pseudospins of the superconductor induces coherent dynamics of the Higgs (amplitude) mode Δ (t ) . We validate this picture in a two-dimensional BCS model with a combination of exact numerics and the Lax reduction method, and we compute the nonequilibrium phase diagram as a function of the pump intensity. The main effect of the pump is to scramble the orientations of Anderson pseudospins along the Fermi surface by twisting them in the x y plane. We show that more intense pump pulses can induce a far-from-equilibrium phase of gapless superconductivity ("phase I"), originally predicted in the context of interaction quenches in ultracold atoms. We show that the THz pump method can reach phase I at much lower energy densities than an interaction quench, and we demonstrate that Lax reduction (tied to the integrability of the BCS Hamiltonian) provides a general quantitative tool for computing coherent BCS dynamics. We also calculate the Mattis-Bardeen optical conductivity for the nonequilibrium states discussed here.

Correlates of existential well-being and their association with health-related quality of life in breast cancer survivors compared with the general population.

PubMed

Shin, Hae Won; Noh, Dong Young; Lee, Eun Sook; Nam, Seok Jin; Park, Byeong Woo; Ahn, Sei Hyun; Yun, Young Ho

2009-11-01

The aim was to evaluate the correlates of existential well-being (EWB) and investigate the relationship between EWB and health-related quality of life (HRQOL) according to the McGill Quality of Life Questionnaire (MQOL) in breast cancer survivors (BCS) and in the general population. BCS (N = 1,933) recruited from five large hospitals completed a mailed survey, which included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30), Quality of Life Questionnaire Breast Cancer Module (QLQ-BR23) and the MQOL. Reference data were derived from a representative sample of the Korean adult population composed of 500 women selected by a nationwide random route technique. Multiple logistic regression analysis showed that members of the general population with a lower educational status were more likely to report poor EWB. However, among BCS, correlates that were associated with poor EWB included lower monthly income, lower educational status, unemployment and comorbidities. Almost all factors listed on the HRQOL questionnaire were correlated with EWB in BCS as well as in the general population (P < 0.001). Factors listed on the QLQ-C30 that were correlated to a clinically meaningful extent with EWB in the general population included physical functioning, nausea and vomiting, and appetite loss, whereas among BCS, insomnia and distress over hair loss were meaningfully correlated with EWB. Compared with general population, BCS showed different EWB correlates and distinct associations with HRQOL findings. Our data suggest that socio-economic status and comorbidities influence on their EWB.

Longitudinal trends with improvement in quality of life after TVT, TVT O and Burch colposuspension procedures.

PubMed

Drahoradova, Petra; Martan, Alois; Svabik, Kamil; Zvara, Karel; Otava, Martin; Masata, Jaromir

2011-02-01

Comparison of the quality of life (QoL) trends after TVT, TVT O and Burch colposuspension (BCS) procedures and comparison of long-term subjective and objective outcomes. The study included 215 women who underwent a TVT, TVT O or BCS procedure. We monitored QoL after each procedure and the effect of complications on the QoL as assessed by the IQOL questionnaire over a 3-year period. The study was completed by 74.5% of women after TVT, 74.5% after TVT O, and 65.2% after BCS procedure. In the long-term, the QoL improved from 46.9 to 88.7 and remained stable after BCS; after TVT and TVT O, it declined, but only after TVT O was the decline statistically significant compared to BCS. The IQOL for women with post-operative complications has a clear descending tendency. The effect of the complications is highly significant (p<0.001). Only the OAB complication had a statistically significant effect on QoL p<0.001. Preexistent OAB does not negatively affect postoperative results of anti-incontinence surgery. There was a statistically significant decline with the longitudinal values of IQOL with TVT O, but not with TVT or BCS. Anti-incontinence operations significantly improve quality of life for women with MI, but compared to the SI group, the quality of life is worse when measured at a longer time interval after the operation. Anti-incontinence operations significantly improve quality of life, and the difference in preoperative status in the long-term follow-up is demonstrable.

Influences of the Bi2Sr2CaCu2Ox/Ag interface and interfilamentary bridge connections on AC loss of composite wires

NASA Astrophysics Data System (ADS)

Jiang, Zhao-Fei; Xue, Feng; Gou, Xiao-Fan

2018-04-01

The microstructure of Bi2Sr2CaCu2Ox (Bi2212) filamentary composite round wires (RWs) changes to be extremely complicated after heat treatment, with the interface between Bi2212 filaments and Ag matrix being meandering and a lot of bridge connections (BCs) generating between filaments. The influence of such the unique microstructure on the electromagnetic behavior and especially the AC loss has not been far from completely understanding. In this paper, according to the H formulation and on the nonlinear E-J relationship, we developed a finite element model, and further on this model evaluated the current and AC loss of a Bi2212 multifilamentary wire with the rough Bi2212/Ag interface and several BCs between filaments under the alternating magnetic field (Hex(t) = H0sin2πft). Through the comparative study, we found that the penetration magnetic field Hp is a critical turning point and on this base the influences of such the complex microstructure are quite different when the amplitude of applied magnetic field H0 < Hp and when H0 > Hp. The rough interface impacts the current distribution and causes the local heat concentrated at the concave locations. For BCs between Bi2212 filaments, it is most significant that they can share the current and make the current redistribute between filaments. Further for the wire with various types of BCs, the current distribution and the AC loss relative to the wire without BCs (Q / QmagnoBCs) were comprehensively investigated.

Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

PubMed

Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

2014-07-01

The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endoscopic non-technical skills team training: the next step in quality assurance of endoscopy training.

PubMed

Matharoo, Manmeet; Haycock, Adam; Sevdalis, Nick; Thomas-Gibson, Siwan

2014-12-14

To investigate whether novel, non-technical skills training for Bowel Cancer Screening (BCS) endoscopy teams enhanced patient safety knowledge and attitudes. A novel endoscopy team training intervention for BCS teams was developed and evaluated as a pre-post intervention study. Four multi-disciplinary BCS teams constituting BCS endoscopist(s), specialist screening practitioners, endoscopy nurses and administrative staff (A) from English BCS training centres participated. No patients were involved in this study. Expert multidisciplinary faculty delivered a single day's training utilising real clinical examples. Pre and post-course evaluation comprised participants' patient safety awareness, attitudes, and knowledge. Global course evaluations were also collected. Twenty-three participants attended and their patient safety knowledge improved significantly from 43%-55% (P ≤ 0.001) following the training intervention. 12/41 (29%) of the safety attitudes items significantly improved in the areas of perceived patient safety knowledge and awareness. The remaining safety attitude items: perceived influence on patient safety, attitudes towards error management, error management actions and personal views following an error were unchanged following training. Both qualitative and quantitative global course evaluations were positive: 21/23 (91%) participants strongly agreed/agreed that they were satisfied with the course. Qualitative evaluation included mandating such training for endoscopy teams outside BCS and incorporating team training within wider endoscopy training. Limitations of the study include no measure of increased patient safety in clinical practice following training. A novel comprehensive training package addressing patient safety, non-technical skills and adverse event analysis was successful in improving multi-disciplinary teams' knowledge and safety attitudes.

Endoscopic non-technical skills team training: The next step in quality assurance of endoscopy training

PubMed Central

Matharoo, Manmeet; Haycock, Adam; Sevdalis, Nick; Thomas-Gibson, Siwan

2014-01-01

AIM: To investigate whether novel, non-technical skills training for Bowel Cancer Screening (BCS) endoscopy teams enhanced patient safety knowledge and attitudes. METHODS: A novel endoscopy team training intervention for BCS teams was developed and evaluated as a pre-post intervention study. Four multi-disciplinary BCS teams constituting BCS endoscopist(s), specialist screening practitioners, endoscopy nurses and administrative staff (A) from English BCS training centres participated. No patients were involved in this study. Expert multidisciplinary faculty delivered a single day’s training utilising real clinical examples. Pre and post-course evaluation comprised participants’ patient safety awareness, attitudes, and knowledge. Global course evaluations were also collected. RESULTS: Twenty-three participants attended and their patient safety knowledge improved significantly from 43%-55% (P ≤ 0.001) following the training intervention. 12/41 (29%) of the safety attitudes items significantly improved in the areas of perceived patient safety knowledge and awareness. The remaining safety attitude items: perceived influence on patient safety, attitudes towards error management, error management actions and personal views following an error were unchanged following training. Both qualitative and quantitative global course evaluations were positive: 21/23 (91%) participants strongly agreed/agreed that they were satisfied with the course. Qualitative evaluation included mandating such training for endoscopy teams outside BCS and incorporating team training within wider endoscopy training. Limitations of the study include no measure of increased patient safety in clinical practice following training. CONCLUSION: A novel comprehensive training package addressing patient safety, non-technical skills and adverse event analysis was successful in improving multi-disciplinary teams’ knowledge and safety attitudes. PMID:25516665

Cell-cell and cell-surface interactions mediated by cellulose and a novel exopolysaccharide contribute to Pseudomonas putida biofilm formation and fitness under water-limiting conditions.

PubMed

Nielsen, Lindsey; Li, Xiaohong; Halverson, Larry J

2011-05-01

The composition of the exopolysaccharide matrix of Pseudomonas putida mt2 biofilms is relatively undefined as well as the contributions of each polymer to ecological fitness. Here, we describe the role of two putative exopolysaccharide gene clusters, putida exopolysaccharide A (pea) and bacterial cellulose (bcs) in biofilm formation and stability, rhizosphere colonization and matrix hydration under water-limiting conditions. Our findings suggest that pea is involved in the production of a novel glucose, galactose, and mannose-rich polymer that contributes to cell-cell interactions necessary for pellicle and biofilm formation and stability. In contrast, Bcs plays a minor role in biofilm formation and stability, although it does contribute to rhizosphere colonization based on a competition assay. We show that pea expression is highly induced transiently under water-limiting conditions but only slightly by high osmolarity, as determined by qRT-PCR. In contrast, both forms of water stress highly induced bcs expression. Cells deficient in making one or more exopolysaccharide experienced greater dehydration-mediated cell-envelope stress, leading to increased alginate promoter activity. However, this did not lead to increased exopolysaccharide production, except in bcs or pea mutants unable to produce alginate, indicating that P. putida compensates by producing, presumably more Pea or Bcs exopolysaccharides, to facilitate biofilm hydration. Collectively, the data suggest that Pea and Bcs contribute to biofilm formation and in turn their presence contributes to fitness under water-limiting conditions, but not to the extent of alginate. © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

BCS-Bose model of exotic superconductors: Generalized coherence length

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casas, M.; Getino, J.M.; de Llano, M.

1994-12-01

Analytic expressions are derived for the root-mean-square (rms) radius of a pair of fermions in a BCS many-fermion state in one, two, and three dimensions, in terms of the BCS gap energy and the associated chemical potential. These expressions are valid for any coupling strength of [ital any] pair interaction model implying a momentum-independent gap energy. The latter holds, e.g., for an attractive [delta] pair potential examined in the one-dimensional (1D) case (whose [ital N]-fermion ground state can be determined exactly) or for the BCS (electron-phonon) model interaction in any dimension. Weak-coupling and/or high-density limits for the rms radius aremore » identical in 1D, 2D, and 3D, and reduce to the familiar well-known Pippard result to within a factor of order unity. In contrast, strong-coupling and/or low-density limits coincide in 1D and 3D, but differ by a factor of order unity in the 2D limit, and in each case are essentially the size of a single, isolated pair. The 1D [delta] interaction McGuire-Yang-Gaudin many-fermion model is studied in detail. The interaction renormalization scheme of Miyake and of Randeria, Duan, and Shieh, and the BCS interaction model, both in 2D, are employed to analyze cuprate superconductor empirical results. Reasonable agreement between theoretical rms radii with experimental coherence lengths suggests that cuprates can be described moderately well as [ital weakly] [ital coupled] superconductors within the BCS-Bose formalism.« less

Self-esteem in adolescents with Angle Class I, II and III malocclusion in a Peruvian sample.

PubMed

Florián-Vargas, Karla; Honores, Marcos J Carruitero; Bernabé, Eduardo; Flores-Mir, Carlos

2016-01-01

To compare self-esteem scores in 12 to 16-year-old adolescents with different Angle malocclusion types in a Peruvian sample. A cross-sectional study was conducted in a sample of 276 adolescents (159, 52 and 65 with Angle Class I, II and III malocclusions, respectively) from Trujillo, Peru. Participants were asked to complete the Rosenberg Self-Esteem Scale (RSES) and were also clinically examined, so as to have Angle malocclusion classification determined. Analysis of covariance (ANCOVA) was used to compare RSES scores among adolescents with Class I, II and III malocclusions, with participants' demographic factors being controlled. Mean RSES scores for adolescents with Class I, II and III malocclusions were 20.47 ± 3.96, 21.96 ± 3.27 and 21.26 ± 4.81, respectively. The ANCOVA test showed that adolescents with Class II malocclusion had a significantly higher RSES score than those with Class I malocclusion, but there were no differences between other malocclusion groups. Supplemental analysis suggested that only those with Class II, Division 2 malocclusion might have greater self-esteem when compared to adolescents with Class I malocclusion. This study shows that, in general, self-esteem did not vary according to adolescents' malocclusion in the sample studied. Surprisingly, only adolescents with Class II malocclusion, particularly Class II, Division 2, reported better self-esteem than those with Class I malocclusion. A more detailed analysis assessing the impact of anterior occlusal features should be conducted.

Occlusal status in Asian male adults: prevalence and ethnic variation.

PubMed

Soh, Jen; Sandham, Andrew; Chan, Yiong Huak

2005-09-01

The purpose of this study was to determine the occlusal status in young Asian male adults of three ethnic groups. Study models of a sample of male army recruits (N = 339, age 17-22 years) with no history of orthodontic treatment were assessed. The ethnic proportions of the sample were Chinese 76.1% (n = 258), Malay 17.7% (n = 60), and Indian 6.2% (n = 21). British Standard Institute (BSI) and Angle's classification were used to determine incisor and molar relationships, respectively. Chi-square test or Fisher's Exact test was performed to compare the occlusal traits between ethnic groups. The distribution of incisor relationships of the total sample consisted of Class I = 48.1%, Class II/1 = 26.3%, Class II/2 = 3.2%, and Class III = 22.4%. Right Angle's molar relationships were 49.9%, 24.5%, and 24.2% whereas left Angle's molar relationships were 53.1%, 25.1%, and 21.2% for Class I, II, and III, respectively. Comparison between ethnic groups found that Indian subjects were more likely to have Class II/1 malocclusions and clinically missing permanent teeth (P < .05). The study found that the overall prevalence of malocclusion (BSI) was Class I, Class II/1, Class III, and Class II/2 in descending order of proportions. Angle's Class I molar was most prevalent followed by Class II and Class III relations. A significant difference in occlusal status between the ethnic groups was found regarding incisor relationship and missing permanent teeth (P < .05).

Levels and determinants of breast and cervical cancer screening uptake in HIV-infected women compared with the general population in France.

PubMed

Tron, L; Lert, F; Spire, B; Dray-Spira, R

2017-03-01

Cancer is a growing concern for HIV-infected people, and screening plays a major role in alleviating the burden it causes. We sought to investigate the levels and determinants of breast cancer screening (BCS) and cervical cancer screening (CCS) in HIV-infected women as compared with the general population. The Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS)-Vespa2 study was conducted in 2011 in a national representative sample of 3022 HIV-infected hospital out-patients in France. The rates and correlates of BCS and CCS among HIV-infected women were compared with those in the general population using multivariate Poisson regression models. The BCS rate during the 2 years preceding the survey interview was 80.7% among HIV-infected women vs. 89.1% in the general population (P = 0.146). The CCS rate during the preceding 3 years was 88.1% among HIV-infected women vs. 83.1% in the general population (P = 0.021). During the preceding year, the CCS rate among HIV-infected women was 76.5%. The barriers to BCS and CCS were a low educational level [BCS: adjusted prevalence rate ratio 0.88; 95% confidence interval (CI) 0.80-0.97; CCS: adjusted prevalence rate ratio 0.91; 95% CI 0.83-0.99], not having supplementary health insurance (CCS: adjusted prevalence rate ratio 0.92; 95% CI 0.86-0.98), an irregular gynaecological follow-up (BCS: adjusted prevalence rate ratio 0.77; 95% CI 0.64-0.92; CCS: adjusted prevalence rate ratio 0.72; 95% CI 0.64-0.81) and a low CD4 count (BCS: adjusted prevalence rate ratio 0.83; 95% CI 0.71-0.97; CCS: adjusted prevalence rate ratio 0.78; 95% CI 0.63-0.98). The disparities in CCS uptake in terms of age, employment and gynaecological follow-up were less pronounced among HIV-infected women than in the general population. BCS and CCS uptake was not lower among HIV-infected women than in the general population, but CCS was suboptimal. Specificities in the profile of barriers to screening emerged. © 2016 British HIV Association.

Increased body condition score through increased lean muscle, but not fat deposition, is associated with reduced reproductive response to oestrus induction in beef cows.

PubMed

Guzmán, A; Gonzalez-Padilla, E; Garcés-Yepez, P; Rosete-Fernández, J V; Calderón-Robles, R C; Whittier, W D; Keisler, D H; Gutierrez, C G

2016-10-01

Energy reserve, estimated as body condition score (BCS), is the major determinant of the re-initiation of ovarian activity in postpartum cows. Leptin, IGF-I and insulin are positively related to BCS and are putative mediators between BCS and reproductive function. However, when BCS and body composition dissociates, concentrations of these metabolic hormones are altered. We hypothesized that increasing lean muscle tissue, but not fat tissue, would diminish the reproductive response to oestrus induction treatments. Thirty lactating beef cows with BCS of 3.10±1.21 and 75.94±12 days postpartum were divided in two groups. Control cows (n=15) were supplemented with 10.20 kg of concentrate daily for 60 days. Treated cows (n=15) were supplemented equally, and received a β-adrenergic receptor agonist (β-AA; 0.15 mg/kg BW) to achieve accretion of lean tissue mass and not fat tissue mass. Twelve days after ending concentrate supplementation/β-AA treatment, cows received a progestin implant to induce oestrus. Cows displaying oestrus were inseminated during the following 60 days, and maintained with a fertile bull for a further 21 days. Cows in both groups gained weight during the supplementation period (Daily weight gain: Control=0.75 kg v. β-AA=0.89 kg). Cows treated with β-AA had a larger increase in BCS (i.e. change in BCS: control=1 point (score 4.13) v. β-AA=2 points (score 5.06; P0.05) did not differ between groups. However, the number of cows displaying oestrus (control 13/15 v. β-AA 8/15; P<0.05) and the percentage cycling (control 6/8 v. β-AA 3/10; P=0.07) after progestin treatment and the pregnancy percentage at the end of the breeding period (control 13/15 v. β-AA 8/15; P<0.05) were lower in β-AA than control cows. In summary, the increase BCS through muscle tissue accretion, but not through fat tissue accretion, resulted in a lower response to oestrus induction, lower percentage of cycling animals and lower pregnancy percentage after progestin treatment; which was associated with a decrease in serum concentrations of leptin and IGF-I.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

PubMed

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-11-09

With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

Sequence, distribution and chromosomal context of class I and class II pilin genes of Neisseria meningitidis identified in whole genome sequences

PubMed Central

2014-01-01

Background Neisseria meningitidis expresses type four pili (Tfp) which are important for colonisation and virulence. Tfp have been considered as one of the most variable structures on the bacterial surface due to high frequency gene conversion, resulting in amino acid sequence variation of the major pilin subunit (PilE). Meningococci express either a class I or a class II pilE gene and recent work has indicated that class II pilins do not undergo antigenic variation, as class II pilE genes encode conserved pilin subunits. The purpose of this work was to use whole genome sequences to further investigate the frequency and variability of the class II pilE genes in meningococcal isolate collections. Results We analysed over 600 publically available whole genome sequences of N. meningitidis isolates to determine the sequence and genomic organization of pilE. We confirmed that meningococcal strains belonging to a limited number of clonal complexes (ccs, namely cc1, cc5, cc8, cc11 and cc174) harbour a class II pilE gene which is conserved in terms of sequence and chromosomal context. We also identified pilS cassettes in all isolates with class II pilE, however, our analysis indicates that these do not serve as donor sequences for pilE/pilS recombination. Furthermore, our work reveals that the class II pilE locus lacks the DNA sequence motifs that enable (G4) or enhance (Sma/Cla repeat) pilin antigenic variation. Finally, through analysis of pilin genes in commensal Neisseria species we found that meningococcal class II pilE genes are closely related to pilE from Neisseria lactamica and Neisseria polysaccharea, suggesting horizontal transfer among these species. Conclusions Class II pilins can be defined by their amino acid sequence and genomic context and are present in meningococcal isolates which have persisted and spread globally. The absence of G4 and Sma/Cla sequences adjacent to the class II pilE genes is consistent with the lack of pilin subunit variation in these isolates, although horizontal transfer may generate class II pilin diversity. This study supports the suggestion that high frequency antigenic variation of pilin is not universal in pathogenic Neisseria. PMID:24690385

Comparison of second molar eruption patterns in patients with skeletal Class II and skeletal Class I malocclusions.

PubMed

Brin, Ilana; Camasuvi, Semin; Dali, Nasser; Aizenbud, Dror

2006-12-01

The eruptive positions of the second molars in Class I and Class II malocclusions were studied. Pretreatment records of 221 patients with a mean age of 11.3 years were evaluated. About 19% of them had skeletal Class I, 31% had skeletal maxillary Class II, and 50% had skeletal mandibular Class II malocclusions. The mean values of the dental and chronologic ages of the subjects were similar. The eruptive positions in relation to a reference line, the developmental stages of the patients' second molars and dental ages were recorded from the panoramic roentgenograms. The distribution of the various developmental stages in each malocclusion group was similar, and no association between skeletal malocclusion and dental developmental stage of the second molars was encountered. The eruptive position of the maxillary second molars was more occlusal only in the oldest maxillary Class II group, above 12 years of age (P = .02). These results support, in part, previous reports suggesting that the maxillary second molars may erupt earlier in patients with skeletal maxillary Class II malocclusions.

Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

PubMed Central

Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

2015-01-01

Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

Core structure of two-dimensional Fermi gas vortices in the BEC-BCS crossover region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madeira, Lucas; Gandolfi, Stefano; Schmidt, Kevin E.

2017-05-02

We report T = 0 diffusion Monte Carlo results for the ground-state and vortex excitation of unpolarized spin-1/2 fermions in a two-dimensional disk. We investigate how vortex core structure properties behave over the BEC-BCS crossover. We calculate the vortex excitation energy, density pro les, and vortex core properties related to the current. We nd a density suppression at the vortex core on the BCS side of the crossover and a depleted core on the BEC limit. Size-effect dependencies in the disk geometry were carefully studied.

Size-dependent bending modulus of nanotubes induced by the imperfect boundary conditions

PubMed Central

Zhang, Jin

2016-01-01

The size-dependent bending modulus of nanotubes, which was widely observed in most existing three-point bending experiments [e.g., J. Phys. Chem. B 117, 4618–4625 (2013)], has been tacitly assumed to originate from the shear effect. In this paper, taking boron nitride nanotubes as an example, we directly measured the shear effect by molecular dynamics (MD) simulations and found that the shear effect is not the major factor responsible for the observed size-dependent bending modulus of nanotubes. To further explain the size-dependence phenomenon, we abandoned the assumption of perfect boundary conditions (BCs) utilized in the aforementioned experiments and studied the influence of the BCs on the bending modulus of nanotubes based on MD simulations. The results show that the imperfect BCs also make the bending modulus of nanotubes size-dependent. Moreover, the size-dependence phenomenon induced by the imperfect BCs is much more significant than that induced by the shear effect, which suggests that the imperfect BC is a possible physical origin that leads to the strong size-dependence of the bending modulus found in the aforementioned experiments. To capture the physics behind the MD simulation results, a beam model with the general BCs is proposed and found to fit the experimental data very well. PMID:27941866

Disorder effects in the evolution from BCS to BEC superfluidity

NASA Astrophysics Data System (ADS)

Han, Li; de Melo, Carlos A. R. Sa

2009-03-01

We discuss the effects of disorder on the critical temperature of superfluids during the evolution from BCS to BEC. For s-wave superfluids we find that the critical temperature is weakly affected by disorder in the BCS regime as described in Anderson’s theorem, even less affected by disorder at zero chemical potential (near unitarity), but strongly affected by disorder in the BEC regime, where Anderson's theorem does not apply. This suggests that the superfluid is more robust to the effects of disorder at the interaction parameter where the chemical potential vanishes (close to unitarity). We construct a three dimensional phase diagram of critical temperature, disorder and interaction parameter [1], and show that there are regions of localized superfluidity, as well as insulating regions due to Anderson localization of fermions (BCS regime) and molecular bosons (BEC regime). The phase diagram for higher angular momentum (e.g. p-wave and d-wave) is also analyzed, where the effects of disorder are much more dramatic in the BCS regime in comparison to the s-wave case because pair breaking is strong, while the disorder effects in BEC regime are similar to what occurs in the s-wave case. [1] Li Han, C. A. R. Sa de Melo, arXiv:0812.xxxx

The BCS-BEC crossover: From ultra-cold Fermi gases to nuclear systems

NASA Astrophysics Data System (ADS)

Strinati, Giancarlo Calvanese; Pieri, Pierbiagio; Röpke, Gerd; Schuck, Peter; Urban, Michael

2018-04-01

This report addresses topics and questions of common interest in the fields of ultra-cold gases and nuclear physics in the context of the BCS-BEC crossover. By this crossover, the phenomena of Bardeen-Cooper-Schrieffer (BCS) superfluidity and Bose-Einstein condensation (BEC), which share the same kind of spontaneous symmetry breaking, are smoothly connected through the progressive reduction of the size of the fermion pairs involved as the fundamental entities in both phenomena. This size ranges, from large values when Cooper pairs are strongly overlapping in the BCS limit of a weak inter-particle attraction, to small values when composite bosons are non-overlapping in the BEC limit of a strong inter-particle attraction, across the intermediate unitarity limit where the size of the pairs is comparable with the average inter-particle distance. The BCS-BEC crossover has recently been realized experimentally, and essentially in all of its aspects, with ultra-cold Fermi gases. This realization, in turn, has raised the interest of the nuclear physics community in the crossover problem, since it represents an unprecedented tool to test fundamental and unanswered questions of nuclear many-body theory. Here, we focus on the several aspects of the BCS-BEC crossover, which are of broad joint interest to both ultra-cold Fermi gases and nuclear matter, and which will likely help to solve in the future some open problems in nuclear physics (concerning, for instance, neutron stars). Similarities and differences occurring in ultra-cold Fermi gases and nuclear matter will then be emphasized, not only about the relative phenomenologies but also about the theoretical approaches to be used in the two contexts. Common to both contexts is the fact that at zero temperature the BCS-BEC crossover can be described at the mean-field level with reasonable accuracy. At finite temperature, on the other hand, inclusion of pairing fluctuations beyond mean field represents an essential ingredient of the theory, especially in the normal phase where they account for precursor pairing effects. After an introduction to present the key concepts of the BCS-BEC crossover, this report discusses the mean-field treatment of the superfluid phase, both for homogeneous and inhomogeneous systems, as well as for symmetric (spin- or isospin-balanced) and asymmetric (spin- or isospin-imbalanced) matter. Pairing fluctuations in the normal phase are then considered, with their manifestations in thermodynamic and dynamic quantities. The last two Sections provide a more specialized discussion of the BCS-BEC crossover in ultra-cold Fermi gases and nuclear matter, respectively. The separate discussion in the two contexts aims at cross communicating to both communities topics and aspects which, albeit arising in one of the two fields, share a strong common interest.

Health and body condition of lactating females on rabbit farms.

PubMed

Sánchez, J P; de la Fuente, L F; Rosell, J M

2012-07-01

The aim was to study relationships between morbidity, defined through prevalence of diseases of rabbit females, and BCS, and to assess the effect of several risk factors on both morbidity and BCS. Our study was based on individual examinations of 18,510 does in lactation on 103 farms. We evaluated BCS on a linear scale from 1 to 9, with 5 being the optimum. Prevalence of major diseases were 22.7%, 4.0%, and 6.4% for coryza, mastitis, and ulcerative pododermatitis, respectively. In addition, prevalence was 3.0% for diseases of minor presentation, including mange, which had a prevalence of 1.9%. The BCS of the R line (selected for growth) was 5.55 ± 0.14, whereas for the A line (selected for litter size) it was 4.40 ± 0.11. Females with more than 20 kindlings had on average a BCS 0.25 ± 0.07 units less than those in the 12th lactation (P = 0.0002). Optimal BCS 4.60 ± 0.11 was reached during the third lactation week. Sick females had a BCS of 0.6 ± 0.01 units less than healthy females. Females with a footrest had on average a BCS 0.19 ± 0.05 units greater than those without. The absence of footrests was an enabling risk factor for ulcerative pododermatitis, the prevalence of which increased by 53%. Ulcerative pododermatitis was associated (P = 0.045) with diet; females consuming a rich energy diet were prone to having this disorder; 1 SD increase in DE (0.32 MJ) determined an increase in ulcerative pododermatitis prevalence of 0.8 percentage points. Diet was not an enabling risk factor for the other diseases. The genetic type to which a female belongs is a predisposing risk factor of disease; P, V and H were also maternal lines, while S group was exclusively formed by maternal lines. With regard to coryza, the S group had the greatest prevalence (44.0%), followed by A, P, R (19.0 to 21.0%); the V line, selected for prolificacy, showed the least prevalence (12.0%). For the case of mastitis although significant (P < 0.05), the magnitude of the differences between disease prevalence was less; R line had a mastitis prevalence of 11.0% while the least prevalence was observed for V does (4.0%). Simultaneous evaluation of both BCS and morbidity on the rabbit farm is recommended for the right assessment of welfare conditions. In this study, the relationships between both variables have been shown, as well as how other intrinsic and extrinsic risk factors modulate these variables; and thus, these factors should be considered during a welfare assessment.

The Ia.2 Epitope Defines a Subset of Lipid Raft Resident MHC Class II Molecules Crucial to Effective Antigen Presentation1

PubMed Central

Busman-Sahay, Kathleen; Sargent, Elizabeth; Harton, Jonathan A.; Drake, James R.

2016-01-01

Previous work has established that binding of the 11-5.2 anti-I-Ak mAb, which recognizes the Ia.2 epitope on I-Ak class II molecules, elicits MHC class II signaling, whereas binding of two other anti-I-Ak mAb that recognize the Ia.17 epitope fail to elicit signaling. Using a biochemical approach, we establish that the Ia.2 epitope recognized by the widely used 11-5.2 mAb defines a subset of cell surface I-Ak molecules predominantly found within membrane lipid rafts. Functional studies demonstrate that the Ia.2 bearing subset of I-Ak class II molecules is critically necessary for effective B cell–T cell interactions especially at low antigen doses, a finding consistent with published studies on the role of raft-resident class II molecules in CD4 T cell activation. Interestingly, B cells expressing recombinant I-Ak class II molecules possessing a β chain-tethered HEL peptide lack the Ia.2 epitope and fail to partition into lipid rafts. Moreover, cells expressing Ia.2 negative tethered peptide-class II molecules are severely impaired in their ability to present both tethered peptide or peptide derived from exogenous antigen to CD4 T cells. These results establish the Ia.2 epitope as defining a lipid raft-resident MHC class II confomer vital to the initiation of MHC class II restricted B cell–T cell interactions. PMID:21543648

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

The association of serum β-hydroxybutyrate concentration with fetal number and health indicators in late-gestation ewes in commercial meat flocks in Prince Edward Island.

PubMed

Ratanapob, Niorn; VanLeeuwen, John; McKenna, Shawn; Wichtel, Maureen; Rodriguez-Lecompte, Juan C; Menzies, Paula; Wichtel, Jeffrey

2018-06-01

Late-gestation ewes are susceptible to ketonemia resulting from high energy requirement for fetal growth during the last few weeks of pregnancy. High lamb mortality is a possible consequence of effects of ketonemia on both ewes and lambs. Determining risk factors to ketonemia is a fundamental step to identify ewes at risk, in order to avoid losses caused by ketonemia. Serum β-hydroxybutyrate (BHBA) concentrations of 384 late-gestation ewe samples were determined. Physical examinations, including body condition, FAMACHA © and hygiene scoring, were performed. Udders and teeth were also examined. Fecal floatation was performed to detect gastrointestinal helminth eggs of the ewe fecal samples. General feeding management practices and season at sampling were recorded. Litter sizes were retrieved from lambing records. Factors associated with log serum BHBA concentration were determined using a linear mixed model, with flock and lambing groups as random effects. The mean serum BHBA concentration was 545.8 (±453.3) μmol/l. Ewes with a body condition score (BCS) of 2.5-3.5 had significantly lower log BHBA concentrations than ewes with a BCS of ≤2.0, by 19.7% (p = 0.035). Ewes with a BCS of >3.5 had a trend toward higher log BHBA concentrations compared to ewes with a BCS of 2.5-3.5. Ewes with a FAMACHA © score of 3 had significantly higher log BHBA concentrations than ewes with a FAMACHA © score of 1 or 2, by 12.1% (p = 0.049). Ewes in which gastrointestinal helminth eggs were detected had significantly higher log BHBA concentrations than ewes in which helminth eggs were not detected, by 12.3% (p = 0.040). An increased litter size was associated with higher log BHBA concentration (p ≤ 0.003), with the log BHBA concentrations of ewes having twins, triplets, and quadruplets or quintuplets were higher than those of ewes having singleton by 19.2%, 30.4%, and 85.2%, respectively. Season at sampling confounded the association between log BHBA concentration and FAMACHA © score, and therefore was retained in the final model even though it was not statistically significant. Intra-class correlation coefficients at the flock and lambing group levels were 0.14 and 0.32, respectively. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Body traits, carcass characteristics and price of cull cows as affected by farm type, breed, age and calving to culling interval.

PubMed

Gallo, L; Sturaro, E; Bittante, G

2017-04-01

Beef production from cull cows is an additional source of income for dairy farms and greatly contributes to red meat production, but the sources of variation of live animal characteristics and the carcass traits of cull cows have rarely been examined. This study investigated the effects of the farm type, breed, age at slaughter (AGE) and calving to culling interval (Calv_Cull) on the body traits and carcass characteristics of dairy and dual-purpose cull cows. Data from 555 cull cows from 182 herds belonging to five farm types, characterised by a combination of housing and feeding systems, were recorded and analysed. Dairy breeds, such as Holstein Friesian and Brown Swiss, and dual-purpose breeds (Simmental, Rendena) were included in the trait assessments. The day before slaughter, the cows were weighed and scored for body condition (BCS) and fleshiness, and then, their heart girth and wither height were measured. At the slaughterhouse, the carcass weight (CW), dressing percentage (DP), carcass conformation and fatness scores, carcass price per kg and carcass total value were obtained. On average, the cows were slaughtered at nearly 71±27 months of age, 285±187 days after the last calving; 615±95 kg BW; and provided a 257±51 kg CW. Nearly 50% of the cows fell within the BCS range of 2.75 to 3.50, and the carcasses were mostly graded in the lowest class of conformation and fatness scores. Cull cows from free-stall farms had a higher DP, carcass conformation score and price than those from traditional tie-stall farms. The breed influenced the AGE, live animal characteristics and carcass traits. Cows from dairy breeds were younger at slaughter, had a lower BCS and fleshiness, and greater body measurements, but a lower DP and carcass price than those from dual-purpose breeds, although differences between the breeds were found within both groups. The age of the cows at slaughter influenced the Calv_Cull and increased the BW, body measurements and CW, but not the fleshiness and fatness appreciation (both in vivo and postmortem) or carcass price. The increasing Calv_Cull improved the BW, BCS, fleshiness, CW and carcass conformation and fatness. In conclusion, the decision to cull dairy cows should also take into account the factors that affect their carcass value in regards to improving the carcass price of cows.

HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition

PubMed Central

Hossain, Azim; God, Jason M.; Radwan, Faisal F. Y.; Amria, Shereen; Zhao, Dan; Bethard, Jennifer R.; Haque, Azizul

2011-01-01

While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL) have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s) have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity. PMID:22162713

The COSMAM TRIAL a prospective cohort study of quality of life and cosmetic outcome in patients undergoing breast conserving surgery.

PubMed

Catsman, Coriene J L M; Beek, Martinus A; Voogd, Adri C; Mulder, Paul G H; Luiten, Ernest J T

2018-04-23

Cosmetic result in breast cancer surgery is gaining increased interest. Currently, some 30-40% of the patients treated with breast conserving surgery (BCS) are dissatisfied with their final cosmetic result. In order to prevent disturbing breast deformity oncoplastic surgical techniques have been introduced. The extent of different levels of oncoplastic surgery incorporated in breast conserving surgery and its value with regard to cosmetic outcome, patient satisfaction and quality of life remains to be defined. The aim of this prospective cohort study is to investigate quality of life and satisfaction with cosmetic result in patients with breast cancer, undergoing standard lumpectomy versus level I or II oncoplastic breast conserving surgery. Female breast cancer patients scheduled for BCS, from 18 years of age, referred to our outpatient clinic from July 2015 are asked to participate in this study. General, oncologic and treatment information will be collected. Patient satisfaction will be scored preceding surgery, and at 1 month and 1 year follow up. Photographs of the breast will be used to score cosmetic result both by the patient, an independent expert panel and BCCT.Core software. Quality of life will be measured by using the BREAST-Q BCT, EORTC-QLQ and EQ-5D-5 L questionnaires. The purpose of this prospective study is to determine the clinical value of different levels of oncoplastic techniques in breast conserving surgery, with regard to quality of life and cosmetic result. Analysis will be carried out by objective measurements of the final cosmetic result in comparison with standard breast conserving surgery. The results of this study will be used to development of a clinical decision model to guide the use oncoplastic surgery in future BCS. Central Commission of Human Research (CCMO), The Netherlands: NL54888.015.15. Medical Ethical Commission (METC), Maxima Medical Centre, Veldhoven, The Netherlands: 15.107. Dutch Trial Register: NTR5665 , retrospectively registered, 02-25-2016.

THE SERENDIPITOUS OBSERVATION OF A GRAVITATIONALLY LENSED GALAXY AT z = 0.9057 FROM THE BLANCO COSMOLOGY SURVEY: THE ELLIOT ARC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckley-Geer, E. J.; Lin, H.; Drabek, E. R.

2011-11-20

We report on the serendipitous discovery in the Blanco Cosmology Survey (BCS) imaging data of a z = 0.9057 galaxy that is being strongly lensed by a massive galaxy cluster at a redshift of z = 0.3838. The lens (BCS J2352-5452) was discovered while examining i- and z-band images being acquired in 2006 October during a BCS observing run. Follow-up spectroscopic observations with the Gemini Multi-Object Spectrograph instrument on the Gemini-South 8 m telescope confirmed the lensing nature of this system. Using weak-plus-strong lensing, velocity dispersion, cluster richness N{sub 200}, and fitting to a Navarro-Frenk-White (NFW) cluster mass density profile,more » we have made three independent estimates of the mass M{sub 200} which are all very consistent with each other. The combination of the results from the three methods gives M{sub 200} = (5.1 {+-} 1.3) Multiplication-Sign 10{sup 14} M{sub Sun }, which is fully consistent with the individual measurements. The final NFW concentration c{sub 200} from the combined fit is c{sub 200} = 5.4{sup +1.4}{sub -1.1}. We have compared our measurements of M{sub 200} and c{sub 200} with predictions for (1) clusters from {Lambda}CDM simulations, (2) lensing-selected clusters from simulations, and (3) a real sample of cluster lenses. We find that we are most compatible with the predictions for {Lambda}CDM simulations for lensing clusters, and we see no evidence based on this one system for an increased concentration compared to {Lambda}CDM. Finally, using the flux measured from the [O II]3727 line we have determined the star formation rate of the source galaxy and find it to be rather modest given the assumed lens magnification.« less

A Phase 2 Trial of Once-Weekly Hypofractionated Breast Irradiation: First Report of Acute Toxicity, Feasibility, and Patient Satisfaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dragun, Anthony E., E-mail: aedrag01@louisville.edu; Quillo, Amy R.; Riley, Elizabeth C.

2013-03-01

Purpose: To report on early results of a single-institution phase 2 trial of a 5-fraction, once-weekly radiation therapy regimen for patients undergoing breast-conserving surgery (BCS). Methods and Materials: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins were eligible to receive whole breast radiation therapy to a dose of 30 Gy in 5 weekly fractions of 6 Gy with or without an additional boost. Elective nodal irradiation was not permitted. There were no restrictions on breast size or the use of cytotoxic chemotherapy for otherwise eligible patients. Patientsmore » were assessed at baseline, treatment completion, and at first posttreatment follow-up to assess acute toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and quality of life (European Organization for Research and Treatment of Cancer QLQ-BR23). Results: Between January and September 2011, 42 eligible patients underwent weekly hypofractionated breast irradiation immediately following BCS (69.0%) or at the conclusion of cytotoxic chemotherapy (31.0%). The rates of grade ≥2 radiation-induced dermatitis, pain, fatigue, and breast edema were 19.0%, 11.9%, 9.5%, and 2.4%, respectively. Only 1 grade 3 toxicity—pain requiring a course of narcotic analgesics—was observed. One patient developed a superficial cellulitis (grade 2), which resolved with the use of oral antibiotics. Patient-reported moderate-to-major breast symptoms (pain, swelling, and skin problems), all decreased from baseline through 1 month, whereas breast sensitivity remained stable over the study period. Conclusions: The tolerance of weekly hypofractionated breast irradiation compares well with recent reports of daily hypofractionated whole-breast irradiation schedules. The regimen appears feasible and cost-effective. Additional follow-up with continued accrual is needed to assess late toxicity, cosmesis, and disease-specific outcomes.« less

Mechanisms regulating enhanced HLA class II-mediated CD4+ T cell recognition of human B-cell lymphoma by resveratrol

PubMed Central

RADWAN, FAISAL F. Y.; ZHANG, LIXIA; HOSSAIN, AZIM; DOONAN, BENTLY P.; GOD, JASON; HAQUE, AZIZUL

2015-01-01

Malignant B-cells express measurable levels of HLA class II proteins, but often escape immune recognition by CD4+ T cells. Resveratrol (Resv) has been the focus of numerous investigations due to its potential chemopreventive and anti-cancer effects, but it has never been tested in the regulation of immune components in B-cell tumors. Here, we show for the first time that Resv treatment enhances HLA class II-mediated immune detection of B-cell lymphomas by altering immune components and class II presentation in tumor cells. Resv treatment induced an upregulation of both classical and non-classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT), increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and their subsequent recognition by CD4+ T cells. Mechanistic study demonstrated that Resv treatment activated the recycling class II pathway of Ag presentation through upregulation of Rab 4B protein expression in B-lymphoma cells. These findings suggest that HLA class II-mediated immune recognition of malignant B-cells can be improved by Resv treatment, thus encouraging its potential use in chemoimmunotherapy of B-cell lymphoma. PMID:21854084

Shark class II invariant chain reveals ancient conserved relationships with cathepsins and MHC class II.

PubMed

Criscitiello, Michael F; Ohta, Yuko; Graham, Matthew D; Eubanks, Jeannine O; Chen, Patricia L; Flajnik, Martin F

2012-03-01

The invariant chain (Ii) is the critical third chain required for the MHC class II heterodimer to be properly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells. Here, we report the isolation of the nurse shark Ii gene, and the comparative analysis of Ii splice variants, expression, genomic organization, predicted structure, and function throughout vertebrate evolution. Alternative splicing to yield Ii with and without the putative protease-protective, thyroglobulin-like domain is as ancient as the MHC-based adaptive immune system, as our analyses in shark and lizard further show conservation of this mechanism in all vertebrate classes except bony fish. Remarkable coordinate expression of Ii and class II was found in shark tissues. Conserved Ii residues and cathepsin L orthologs suggest their long co-evolution in the antigen presentation pathway, and genomic analyses suggest 450 million years of conserved Ii exon/intron structure. Other than an extended linker preceding the thyroglobulin-like domain in cartilaginous fish, the Ii gene and protein are predicted to have largely similar physiology from shark to man. Duplicated Ii genes found only in teleosts appear to have become sub-functionalized, as one form is predicted to play the same role as that mediated by Ii mRNA alternative splicing in all other vertebrate classes. No Ii homologs or potential ancestors of any of the functional Ii domains were found in the jawless fish or lower chordates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acculturation levels and personalizing orthognathic surgery for the Asian American patient.

PubMed

Sy, A A; Kim, W S; Chen, J; Shen, Y; Tao, C; Lee, J S

2016-10-01

This study was performed to investigate whether the level of acculturation among Asians living in the USA plays a significant role in their opinion of facial profiles. One hundred and ninety-eight Asian American subjects were asked to complete a pre-validated survey to measure their level of acculturation and to evaluate four sets of pictures that displayed a class II male, class II female, class III male, and class III female. Each set consisted of three lateral profile pictures: an initial unaltered photo, a picture simulating a flatter profile (orthodontic camouflage in class II; mandibular setback in class III), and a picture simulating a fuller profile (mandibular advancement in class II; maxillary advancement in class III). For the class II male, subjects who were more acculturated indicated that a flatter profile (orthodontic camouflage) was less attractive. For the class II female, higher acculturated subjects chose expansive treatment (mandibular advancement) as more aesthetic compared to the less acculturated subjects. Each of these scenarios had statistically significant odds ratios. In general, highly acculturated subjects preferred a fuller facial profile, while low acculturated subjects preferred a flatter facial profile appearance, except for the class III female profile, which did not follow this trend. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Noncovalent fabrication and tunable fusion of block copolymer-giant polyoxometalate hybrid micelles.

PubMed

Zhang, Liying; Li, Haolong; Wu, Lixin

2014-09-21

The block copolymers (BCs), as structure-directing agents, co-assembling with nanoscale inorganic additives is an important route to fabricate nanostructured hybrid materials. In this work, we present a facile approach to fabricate hybrid micelles composed of BCs and polyoxometalates (POMs), in which the POM clusters are premodified with the groups that can specifically interact with a certain BC block. A representative POM (NH4)42[Mo(132)O(372)(CH(3)COO)(30)(H2O)72] (Mo(132)) is chosen as the example and encapsulated with cationic molecules containing carboxyphenyl groups through electrostatic interactions, and then the resulting hybrid complex can further co-assemble with poly(styrene-block-4-vinylpyridine) (PS-b-P4VP) through hydrogen bonding with the pyridine groups, which leads to the formation of hybrid micelles and the localization of Mo(132) in the micelle cores. The micelles exhibit a high stability despite time and dilution. Furthermore, the fusion of the micelles can be readily adjusted by varying the length of PS blocks, which is promising to be used in constructing polymer-POM hybrid materials with discrete or continuous hybrid domains. This work is based on the electrostatic premodification of POMs and thus its concept is generally suitable for the whole anionic POM system, which may create a large class of BC-POM nanocomposites with tunable structures.

Evaluation of Intestinal Absorption and Bioavailability of a Bergenin-Phospholipid Complex Solid Dispersion in Rats.

PubMed

Gao, Haoshi; Wei, Yue; Xi, Long; Sun, Yuanyuan; Zhang, Tianhong

2018-05-01

Bergenin (BN) is a Biopharmaceutics Classification System class IV (BCS IV) drug with poor hydrophilicity and lipophilicity and is potentially eliminated by the efflux function of P-glycoprotein (P-gp). These factors may explain its low oral bioavailability. In the present study, a BN-phospholipid complex solid dispersion (BNPC-SD) was prepared by solvent evaporation and characterized based on differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, infrared diffraction, solubility, octanol-water partition coefficient, and in vitro dissolution. To investigate how P-gp can inhibit BN absorption in vivo, the P-gp inhibitor verapamil was co-administered with BNPC-SD to Sprague Dawley rats. By in situ single-pass intestinal perfusion, the membrane permeability of BN from BNPC-SD was higher than that of BN given alone and was improved further by co-administered verapamil. A pharmacokinetics study was done in Sprague Dawley rats, with plasma BN levels estimated by high-performance liquid chromatography. C max and AUC 0 → t values for BN were significantly higher for BNPC-SD than for BN given alone and were increased further by verapamil. Thus, the relative oral bioavailability of BNPC-SD as well as BNPC-SD co-administered with verapamil was 156.33 and 202.46%, respectively, compared with the value for BN given alone. These results showed that BNPC-SD can increase the oral bioavailability of BCS IV drugs.

Evaluation of skeletal and dental asymmetries in Angle Class II subdivision malocclusions with cone-beam computed tomography.

PubMed

Minich, Craig M; Araújo, Eustáquio A; Behrents, Rolf G; Buschang, Peter H; Tanaka, Orlando M; Kim, Ki Beom

2013-07-01

The purpose of this study was to determine whether Angle Class II subdivision malocclusions have skeletal or dental asymmetries between the Class II and Class I sides. A sample of 54 untreated Angle Class II subdivision patients with pretreatment photos and cone-beam computed tomography (CBCT) scans was used. The photos were used to identify the Class II subdivision malocclusion and to record the amount of crowding per quadrant. Landmarks were plotted on each CBCT volume so that direct 3-dimensional measurements could be made to compare the positions and dimensions of the skeletal and dental structures on the Class II side vs the Class I side. Significant differences were found for 2 skeletal measurements: the position of the maxilla relative to the cranial base, and the mandibular dimension from the mandibular foramen to the mental foramen. Statistically significant dental differences were found for the position of the mandibular first molars and canines in relation to the maxilla and the mandible. Statistically significant differences were found for the maxillary first molars and canines in relation to the mandible. There were significant skeletal and dental differences between the Class I and Class II sides. The dental asymmetries accounted for about two thirds of the total asymmetry. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Omitting radiation therapy after lumpectomy for pure DCIS does not reduce the risk of salvage mastectomy.

PubMed

Rakovitch, Eileen; Nofech-Mozes, Sharon; Hanna, Wedad; Sutradhar, Rinku; Gu, Sumei; Fong, Cindy; Tuck, Alan; Youngson, Bruce; Miller, Naomi; Done, Susan J; Chang, Martin C; Sengupta, Sandip; Elavathil, Leela; Jani, Prashant A; Bonin, Michel; Lalani, Nafisha; Paszat, Lawrence

2018-02-01

Radiation therapy (RT) after breast-conserving surgery (BCS) for Ductal Carcinoma in Situ (DCIS) halves the risk of local recurrence (LR). The omission of RT is often supported by the paradigm that patients who develop LR can be salvaged with further breast-conserving therapy leading to higher rates of breast preservation and improved quality of life. However, population-based, long-term rates of breast preservation in women treated by upfront BCS ± RT are unknown. Women diagnosed with pure DCIS from 1994 to 2003 treated with BCS ± RT in Ontario were identified. Median follow-up is 12 years. The development and treatment of LR and contralateral breast cancers were determined by administrative databases with validation. The 10-year mastectomy-free survival was calculated using the Kaplan-Meier method. The impact of RT on breast preservation was determined by propensity-adjusted cox proportional hazards model. The cohort includes 3303 women with DCIS; 1649 (50%) underwent BCS alone, 1654 (50%) underwent BCS + RT. Women treated by BCS alone were more likely to develop a LR compared to those treated by upfront BCS + RT (20.8% versus 15.5%, p < 0.001). Mastectomy was used to treat LR in 57.4% (197/343) of women who recurred after BCS alone and 67.6% (174/257) of those who recurred after BCS + RT. Women treated with upfront BCS + RT had higher rates of bilateral breast preservation at 10 years compared to those treated by BCS alone (87.3% vs.82.7%, p = 0.0096). Local Recurrence after BCS alone does not favor breast preservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal trends with Improvement in Quality of Life after TVT, TVT O and Burch Colposuspension Procedures

PubMed Central

Drahoradova, Petra; Martan, Alois; Svabik, Kamil; Zvara, Karel; Otava, Martin; Masata, Jaromir

2011-01-01

Summary Background Comparison of the quality of life (QoL) trends after TVT, TVT O and Burch colposuspension (BCS) procedures and comparison of long-term subjective and objective outcomes. Material/Methods The study included 215 women who underwent a TVT, TVT O or BCS procedure. We monitored QoL after each procedure and the effect of complications on the QoL as assessed by the IQOL questionnaire over a 3-year period. Results The study was completed by 74.5% of women after TVT, 74.5% after TVT O, and 65.2% after BCS procedure. In the long-term, the QoL improved from 46.9 to 88.7 and remained stable after BCS; after TVT and TVT O, it declined, but only after TVT O was the decline statistically significant compared to BCS. The IQOL for women with post-operative complications has a clear descending tendency. The effect of the complications is highly significant (p<0.001). Only the OAB complication had a statistically significant effect on QoL p<0.001. Preexistent OAB does not negatively affect postoperative results of anti-incontinence surgery. Conclusions There was a statistically significant decline with the longitudinal values of IQOL with TVT O, but not with TVT or BCS. Anti-incontinence operations significantly improve quality of life for women with MI, but compared to the SI group, the quality of life is worse when measured at a longer time interval after the operation. Anti-incontinence operations significantly improve quality of life, and the difference in preoperative status in the long-term follow-up is demonstrable. PMID:21278690

Effects of supervised exercise on motivational outcomes in breast cancer survivors at 5-year follow-up.

PubMed

Trinh, Linda; Mutrie, Nanette; Campbell, Anna M; Crawford, Jennifer J; Courneya, Kerry S

2014-12-01

Short-term physical activity (PA) has beneficial effects on symptom management and quality of life, however, longer-term adherence is likely needed for improved disease outcomes in breast cancer survivors (BCS). This study examined the effects of a supervised group exercise program on motivational outcomes and PA among BCS at 5-year follow-up. The original study was a two-armed, randomized controlled trial comparing a 12-week supervised group exercise program to usual care among 203 BCS. BCS for this follow-up study were contacted at 60 months postintervention and asked to complete assessments of motivational outcomes from the Theory of Planned Behavior and PA behavior using the Scottish Physical Activity Questionnaire. Overall, 87 participants provided 5-year follow-up data with no differences in participation by group. Analyses of covariance (ANCOVAs) revealed that supervised exercise had a significant positive effect on descriptive norm at 5-year follow-up (mean = +0.6; 95% CI = +0.1 to +1.1; d = +0.48; p = 0.021). Small positive effects were also noted for perceived behavioral control (d = +0.18), instrumental attitude (d = +0.26), and injunctive norm (d = +0.35), although they were not statistically significant. Moreover, BCS who were more active at 5-year follow-up also reported more favorable perceived behavioral control (d = +0.16), instrumental attitude (d = +0.28), injunctive norm (d = +0.24), and descriptive norm (d = +0.31), although these differences were not statistically significant. This trial provides suggestive evidence that a supervised exercise program has positive effects on motivational outcomes even after 5 years. Additional intervention strategies during follow-up may further improve long-term adherence and health outcomes in BCS. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preoperative chemotherapy for T2 breast cancer is associated with improved surgical outcome.

PubMed

Karanlik, H; Ozgur, I; Cabioglu, N; Sen, F; Erturk, K; Kilic, B; Onder, S; Deniz, M; Yavuz, E; Aydiner, A

2015-09-01

The aim of this study is to compare the clinical outcome in T2 breast cancer patients who underwent preoperative chemotherapy (PC) and who did not. The study also tried to define a subgroup of patients, who are more beneficial after PC in terms of lower re-excision rates, better cosmetic results and local recurrence free survival. 251 consecutive patients treated for nonmetastatic T2 invasive breast cancer were analyzed retrospectively. Of those; 141 underwent primary surgery (PS) followed by chemotherapy, whereas 110 were treated with combination of PC and surgery. The patients who were treated with PC had a significantly higher incidence of negative margins and lower rate of re-excision (5% vs. 16%, p = 0.02). Of all patients attempted breast conserving surgery (BCS), patients in the PC group were more likely to undergo BCS as their definitive operation compared to patients with PS group (BCS rates; PC group: 99% vs. PS group: 92%, p = 0.05). Multifocal disease (OR: 7, 95% Cl, 2.7-18.4, p = 0.0001) and PC (OR = 0.2; 95% CI, 0.06-0.72, p = 0.01) were factors associated with margin positivity in patients treated with BCS. There was no statistically significant difference in 5 year local-recurrence free survival rates between 2 groups. Our study shows that PC significantly decreases the re-excision in patients undergoing BCS with primary T2 breast tumors. This data suggests that any patient with a tumor greater than 2 cm might be considered for PC to increase BCS success with final negative margins. Copyright © 2015. Published by Elsevier Ltd.

Comparison of breast-conserving surgery with mastectomy in locally advanced breast cancer after good response to neoadjuvant chemotherapy: A PRISMA-compliant systematic review and meta-analysis.

PubMed

Sun, Yixuan; Liao, Mingjuan; He, Liu; Zhu, Chenfang

2017-10-01

The application of breast-conserving surgery (BCS) on patients with locally advanced breast cancer (LABC) with good response to neoadjuvant chemotherapy (NACT) still remains controversial. The objective in this study is to analyze the safety of BCS in the management of LABC in patients with good response to NACT. We searched the electronic databases of Medline (Pubmed) and Cochrane Library for reports on local recurrence (LR), regional recurrence (RR), distant recurrence (DR), 5-year disease-free survival (DFS) or 5-year overall survival (OS) in patients with LABC receiving BCS or mastectomy (MT) and with good response to NACT. Based on the research results, we conducted a meta-analysis using Review Manager 5.3. Our study showed that 16 studies with a combined total of 3531 patients, of whom 1465 patients underwent BCS, whereas 2066 patients underwent MT. There was no significant heterogeneity among these studies (Q statistic: P = .88; I = 0%). Patients with good response to NACT showed no significant difference in LR and RR [odd ratio (OR) = 0.83; 95% confidence interval (CI): 0.60-1.15; P = .26; OR = 0.56; 95% CI: 0.33-0.93; P = .03], while we figured out a lower DR (OR = 0.51; 95% CI: 0.42-0.63; P < .01), a higher DFS (OR = 2.35; 95% CI: 1.84 to 3.01, P < .01) and a higher OS (OR = 2.12; 95% CI: 1.51 to 2.98, P < .01) in BCS compared with MT. This meta-analysis concluded that BCS was a safe surgery for patients with LABC and had good response to NACT.

Evaluation of the protective effect of Nigella sativa extract and its primary active component thymoquinone against DMBA-induced breast cancer in female rats

PubMed Central

Linjawi, Sabah A. A.; Hassanane, Mahrosa M.; Ahmed, Ekram S.

2013-01-01

Introduction The historical use of black cumin seed (Nigella sativa) dates back centuries, being embedded in Arabian culture and having a long history of unsurpassed medicinal value with versatility to treat a wide range of ailments. Thymoquinone (TQ) is now known to be the primary active constituent of black cumin seed oil (BCS oil) responsible for its medicinal effects and also showing promise for treatment of cancer. Material and methods In the current study, we have studied the effects of TQ and BCS oil on tumor markers (MDA, LDH, ALP and AST), histopathological alterations and the regulation of several genes (Brca1, Brca2, Id-1 and P53 mutation) related to breast cancer in female rats induced by 7,12-dimethylbenz[a]anthracene (DMBA) treatment. Rats received a single dose (65 mg/kg b.w.) of DMBA via an intragastric tube to induce breast cancer. Animals that received DMBA were treated orally with 1, 5, 10 mg/kg of TQ or BCS oil via an intragastric tube three times per week for 4 months. Results We found that TQ and then BCS reduced the rate of tumor markers (levels of MDA and LDH as well as ALP and AST activities), inhibited the histopathological alterations and decreased the expression of the Brca1, Brca2, Id-1 and P53 mutations in mammary tissues of female rats induced by DMBA treatment. Conclusions The results suggest that TQ and BCS oil exert a protective effect against breast carcinogens. The antioxidant property of TQ and BCS oil is mediated by their actions and investigating other underlying mechanisms merits further studies. PMID:25861310

Radiation Therapy After Breast-Conserving Surgery: Does Hospital Surgical Volume Matter? A Population-Based Study in Taiwan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chien, Chun-Ru; Department of Radiation Oncology, China Medical University Hospital, and School of Medicine, China Medical University, Taichung, Taiwan; Pan, I-Wen

2012-01-01

Purpose: To examine the association between hospital surgical volume and the use of radiation therapy (RT) after breast-conserving surgery (BCS) in Taiwan. Methods and Materials: We used claims data from the National Health Insurance program in Taiwan (1997-2005) in this retrospective population-based study. We identified patients with breast cancer, receipt of BCS, use of radiation, and the factors that could potentially associated with the use of RT from enrollment records, and the ICD-9 and billing codes in claims. We conducted logistic regression to examine factors associated with RT use after BCS, and performed subgroup analyses to examine whether the associationmore » differs by medical center status or hospital volumes. Results: Among 5,094 patients with newly diagnosed invasive breast cancer who underwent BCS, the rate of RT was significantly lower in low-volume hospitals (74% vs. 82%, p < 0.01). Patients treated in low-volume hospitals were less likely to receive RT after BCS (odds ratio = 0.72, 95% confidence interval = 0.62-0.83). In addition, patients treated after the implementation of the voluntary pay-for-performance policy in 2001 were more likely to receive RT (odds ratio = 1.23; 95% confidence interval = 1.05-1.45). Subgroup analyses indicated that the high-volume effect was limited to hospitals accredited as non-medical centers, and that the effect of the pay-for-performance policy was most pronounced among low-volume hospitals. Conclusions: Using population-based data from Taiwan, our study concluded that hospital surgical volume and pay-for-performance policy are positively associated with RT use after BCS.« less

Improved BC method of Compomat G4 for expression of BCs twice from whole blood in top and top bags.

PubMed

Deng, Xiao-Yan; Wu, Xiao-Man; Zhao, Yang; Luo, Hong; Jia, Hong-Yun; Wang, Zhong-Ying; He, Bo; Wang, Chuan-Xi

2011-05-01

The aim of this paper was to evaluate an improved buffy coat (BC) method of Compomat G4 for automated expression of BCs twice from whole blood (WB) in top and top (T&T) bags. WB was separated using hard spin centrifugation (2,988g, 10 min) into layers of blood components by specific gravity, and different components were subsequently expressed into satellite bags in the T&T system using the manual BC method, the conventional BC method of G4, and our improved BC method of G4. In the improved BC method, an accessorial device we have named a 'gravity press' was designed and installed on the top flat of G4 to produce gravitational pressure on the plasma bag so as to exclude air and some of plasma to the upper compartment of the slide after BCs were expressed for the first time. The residual BCs in the upper compartment were expressed a second time by extending the upper press once more. All of the pooled BCs were centrifuged by soft spin (402g, 10 min) and upper platelet-rich supernatant was manually expressed into a platelet container by the plasma extractor. In vitro studies of blood components and pooled platelet concentrates (PCs) revealed no significant differences in BC blood components and platelet recovery of pooled platelets (61 ± 9 vs. 60 ± 7%, n = 12, p > 0.05) between the improved BC method and the conventional BC method; all components met our specifications for blood products. We suggest that the new BC method for use of T&T bags may improve the collection of BCs.

25 CFR 522.11 - Individually owned class II gaming operations operating on September 1, 1986.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II gaming operations operating on September 1, 1986. 522.11 Section 522.11 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING...

Glass ionomer-silver cermet Class II tunnel-restorations for primary molars.

PubMed

Croll, T P

1988-01-01

Tunnel preparations preserve the anatomical marginal ridge and minimize the loss of healthy tooth structure adjacent to the carious lesion. When the practitioner has developed proficiency in restoring class II carious lesions with tunnel restorations, less treatment time is required than with traditional class II preparations. The technique for restoring a primary first molar with a class II carious lesion, using a tunnel preparation and Ketac-Silver restorative material is described.

Diversity and evolutionary patterns of immune genes in free-ranging Namibian leopards (Panthera pardus pardus).

PubMed

Castro-Prieto, Aines; Wachter, Bettina; Melzheimer, Joerg; Thalwitzer, Susanne; Sommer, Simone

2011-01-01

The genes of the major histocompatibility complex (MHC) are a key component of the mammalian immune system and have become important molecular markers for fitness-related genetic variation in wildlife populations. Currently, no information about the MHC sequence variation and constitution in African leopards exists. In this study, we isolated and characterized genetic variation at the adaptively most important region of MHC class I and MHC class II-DRB genes in 25 free-ranging African leopards from Namibia and investigated the mechanisms that generate and maintain MHC polymorphism in the species. Using single-stranded conformation polymorphism analysis and direct sequencing, we detected 6 MHC class I and 6 MHC class II-DRB sequences, which likely correspond to at least 3 MHC class I and 3 MHC class II-DRB loci. Amino acid sequence variation in both MHC classes was higher or similar in comparison to other reported felids. We found signatures of positive selection shaping the diversity of MHC class I and MHC class II-DRB loci during the evolutionary history of the species. A comparison of MHC class I and MHC class II-DRB sequences of the leopard to those of other felids revealed a trans-species mode of evolution. In addition, the evolutionary relationships of MHC class II-DRB sequences between African and Asian leopard subspecies are discussed.

77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

...; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...

Comparison of temporomandibular joint and ramus morphology between class II and class III cases before and after bi-maxillary osteotomy.

PubMed

Iguchi, Ran; Yoshizawa, Kunio; Moroi, Akinori; Tsutsui, Takamitsu; Hotta, Asami; Hiraide, Ryota; Takayama, Akihiro; Tsunoda, Tatsuya; Saito, Yuki; Sato, Momoko; Baba, Nana; Ueki, Koichiro

2017-12-01

The purpose of this study was to compare changes in temporomandibular joint (TMJ) and ramus morphology between class II and III cases before and after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. The subjects were 39 patients (78 sides) who underwent bi-maxillary surgery. They consisted of 2 groups (18 class II cases and 21 class III cases), and were selected randomly from among patients who underwent surgery between 2012 and 2016. The TMJ disc tissue and joint effusion were assessed by magnetic resonance imaging (MRI) and the TMJ space, condylar height, ramus height, ramus inclination and condylar square were assessed by computed tomography (CT), pre- and post-operatively. The number of joints with anterior disc displacement in class II was significantly higher than that in class III (p < 0.0001). However, there were no significant differences between the two classes regarding ratio of joint symptoms and ratio of joint effusion pre- and post-operatively. Class II was significantly better than class III regarding reduction ratio of condylar height (p < 0.0001) and square (p = 0.0005). The study findings suggest that condylar morphology could change in both class II and III after bi-maxillary surgery. The findings of the numerical analysis also demonstrated that reduction of condylar volume occurred frequently in class II, although TMJ disc position classification did not change significantly, as previously reported. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Genetics Home Reference: Björnstad syndrome

MedlinePlus

... species, which are harmful molecules that can damage DNA and tissues. BCS1L gene mutations involved in Björnstad syndrome alter the BCS1L protein and impair its ability to aid in complex III formation. The resulting decrease in complex III activity reduces ...

Increased serum leptin and insulin concentrations in canine hypothyroidism.

PubMed

Mazaki-Tovi, Michal; Feuermann, Yonatan; Segev, Gilad; Klement, Eyal; Yas-Natan, Einat; Farkas, Amnon; Kol, Amir; Shamay, Avi

2010-01-01

Serum concentrations of leptin and insulin were compared between gender-matched hypothyroid (n=25) and healthy (n=25) client-owned dogs within comparable age and body condition score (BCS) ranges. Fasted blood samples were collected from each dog and analysed for glucose, cholesterol, triglyceride, leptin and insulin concentrations. Leptin and insulin concentrations were significantly higher in the hypothyroid compared to normal dogs (P=0.006 and P=0.001, respectively) following adjustment for potential confounders. A nearly significant (P=0.051) interaction with BCS was found in the association between hypothyroidism and leptin. Leptin concentrations were significantly higher in hypothyroid dogs compared to normal dogs, in separate analyses for BCS 6 (P=0.036) and 7 (P=0.049). There was no significant difference in glucose concentration between the hypothyroid and normal groups (P=0.84) following adjustment for BCS. This study showed that canine hypothyroidism is associated with increased serum leptin and insulin concentrations, neither of which may be attributed to obesity alone. Copyright 2008 Elsevier Ltd. All rights reserved.

Resonance Properties of Class I and Class II Neurons Differentially Modulated by Channel Noise

NASA Astrophysics Data System (ADS)

Wang, Lei

2018-01-01

Resonance properties of two different neuron types (Class I and Class II) induced by channel noise are investigated in this study. It is found that for Class I neuron, spiking activity is enhanced when certain noise intensity is presented, especially under weak current stimuli -- a typical phenomenon of stochastic resonance (SR); while for Class II neuron, in addition to perform the SR, certain noise intensity would inhibit neuronal activity under some current stimuli -- a typical phenomenon of inverse stochastic resonance (ISR). Moreover, we show that only sodium channel noise or potassium channel noise variation can achieve the similar phenomena. Consequently, the model results suggest that channel noise may exert differential roles in modulating the resonance properties of Class I and Class II neurons.

Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

PubMed

Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

2007-07-01

To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

Influence of pharyngeal airway respiration pressure on Class II mandibular retrusion in children: A computational fluid dynamics study of inspiration and expiration.

PubMed

Iwasaki, T; Sato, H; Suga, H; Takemoto, Y; Inada, E; Saitoh, I; Kakuno, K; Kanomi, R; Yamasaki, Y

2017-05-01

To examine the influence of negative pressure of the pharyngeal airway on mandibular retraction during inspiration in children with nasal obstruction using the computational fluid dynamics (CFD) method. Sixty-two children were divided into Classes I, II (mandibular retrusion) and III (mandibular protrusion) malocclusion groups. Cone-beam computed tomography data were used to reconstruct three-dimensional shapes of the nasal and pharyngeal airways. Airflow pressure was simulated using CFD to calculate nasal resistance and pharyngeal airway pressure during inspiration and expiration. Nasal resistance of the Class II group was significantly higher than that of the other two groups, and oropharyngeal airway inspiration pressure in the Class II (-247.64 Pa) group was larger than that in the Class I (-43.51 Pa) and Class III (-31.81 Pa) groups (P<.001). The oropharyngeal airway inspiration-expiration pressure difference in the Class II (-27.38 Pa) group was larger than that in the Class I (-5.17 Pa) and Class III (0.68 Pa) groups (P=.006). Large negative inspiratory pharyngeal airway pressure due to nasal obstruction in children with Class II malocclusion may be related to their retrognathia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47 000 MW acid labile protein in CD4+ T-cell recognition

PubMed Central

God, Jason M; Zhao, Dan; Cameron, Christine A; Amria, Shereen; Bethard, Jennifer R; Haque, Azizul

2014-01-01

While Burkitt lymphoma (BL) has a well-known defect in HLA class I-mediated antigen presentation, the exact role of BL-associated HLA class II in generating a poor CD4+ T-cell response remains unresolved. Here, we found that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. This defect in CD4+ T-cell recognition was not associated with low levels of co-stimulatory molecules on BL cells, as addition of external co-stimulation failed to elicit CD4+ T-cell activation by BL. Further, the defect was not caused by faulty antigen/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Interestingly, functional class II–peptide complexes were formed at acidic pH 5·5, which restored immune recognition. Acidic buffer (pH 5·5) eluate from BL cells contained molecules that impaired class II-mediated antigen presentation and CD4+ T-cell recognition. Biochemical analysis showed that these molecules were greater than 30 000 molecular weight in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47 000 molecular weight enolase-like molecule that enhances class II-mediated antigen presentation in B cells, macrophages and dendritic cells, but not in BL cells. These findings demonstrate that BL likely has multiple defects in HLA class II-mediated antigen presentation and immune recognition, which may be exploited for future immunotherapies. PMID:24628049

Comprehensive Evaluation of the MBT STAR-BL Module for Simultaneous Bacterial Identification and β-Lactamase-Mediated Resistance Detection in Gram-Negative Rods from Cultured Isolates and Positive Blood Cultures.

PubMed

Lee, Annie W T; Lam, Johnson K S; Lam, Ricky K W; Ng, Wan H; Lee, Ella N L; Lee, Vicky T Y; Sze, Po P; Rajwani, Rahim; Fung, Kitty S C; To, Wing K; Lee, Rodney A; Tsang, Dominic N C; Siu, Gilman K H

2018-01-01

Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module. The results and turnaround times were compared with those of routine microbiological processing. All strains were also characterized by beta-lactamase PCR and sequencing. Results: Using the saponin-based extraction method, MALDI-TOF MS correctly identified bacteria in 116/134 (86.6%) monomicrobial BCs. The detection sensitivities for β-lactamase activities against ampicillin, piperacillin, third-generation cephalosporin and meropenem were 91.3, 100, 97.9, and 100% for cultured isolates, and 80.4, 100, 68.8, and 40% for monomicrobial BCs ( n = 134) respectively. The overall specificities ranged from 91.5 to 100%. Furthermore, the MBT STAR-BL and conventional drug susceptibility test results were concordant in 14/19 (73.7%) polymicrobial cultures. Reducing the logRQ cut-off value from 0.4 to 0.2 increased the direct detection sensitivities for β-lactamase activities against ampicillin, cefotaxime and meropenem in BCs to 85.7, 87.5, and 100% respectively. The MBT STAR-BL test enabled the reporting of β-lactamase-producing GNR at 14.16 and 47.64 h before the interim and final reports of routine BCs processing, respectively, were available. Conclusion: The MALDI Biotyper system equipped with the MBT STAR-BL module enables the simultaneous rapid identification of bacterial species and β-lactamase-mediated resistance from BCs and cultured isolates. Adjustment of the logRQ cut-off value to 0.2 significantly increased the detection sensitivities for clinically important drug-resistant pathogens.

Nickel Availability in Soil as Influenced by Liming and Its Role in Soybean Nitrogen Metabolism

PubMed Central

de Macedo, Fernando G.; Bresolin, Joana D.; Santos, Elcio F.; Furlan, Felipe; Lopes da Silva, Wilson T.; Polacco, Joe C.; Lavres, José

2016-01-01

Nickel (Ni) availability in soil varies as a function of pH. Plants require Ni in small quantities for normal development, especially in legumes due its role in nitrogen (N) metabolism. This study investigated the effect of soil base saturation, and Ni amendments on Ni uptake, N accumulation in the leaves and grains, as well as to evaluate organic acids changes in soybean. In addition, two N assimilation enzymes were assayed: nitrate reductase (NR) and Ni-dependent urease. Soybean plants inoculated with Bradyrhizobium japonicum were cultivated in soil-filled pots under two base-cation saturation (BCS) ratios (50 and 70%) and five Ni rates – 0.0; 0.1; 0.5; 1.0; and 10.0 mg dm-3 Ni. At flowering (R1 developmental stage), plants for each condition were evaluated for organic acids (oxalic, malonic, succinic, malic, tartaric, fumaric, oxaloacetic, citric and lactic) levels as well as the activities of urease and NR. At the end of the growth period (R7 developmental stage – grain maturity), grain N and Ni accumulations were determined. The available soil-Ni in rhizosphere extracted by DTPA increased with Ni rates, notably in BCS50. The highest concentrations of organic acid and N occurred in BCS70 and 0.5 mg dm-3 of Ni. There were no significant differences for urease activity taken on plants grown at BSC50 for Ni rates, except for the control treatment, while plants cultivated at soil BCS70 increased the urease activity up to 0.5 mg dm-3 of Ni. In addition, the highest values for urease activities were reached from the 0.5 mg dm-3 of Ni rate for both BCS treatments. The NR activity was not affected by any treatment indicating good biological nitrogen fixation (BNF) for all plants. The reddish color of the nodules increased with Ni rates in both BCS50 and 70, also confirms the good BNF due to Ni availability. The optimal development of soybean occurs in BCS70, but requires an extra Ni supply for the production of organic acids and for increased N-shoot and grain accumulation. PMID:27660633

Comprehensive Evaluation of the MBT STAR-BL Module for Simultaneous Bacterial Identification and β-Lactamase-Mediated Resistance Detection in Gram-Negative Rods from Cultured Isolates and Positive Blood Cultures

PubMed Central

Lee, Annie W. T.; Lam, Johnson K. S.; Lam, Ricky K. W.; Ng, Wan H.; Lee, Ella N. L.; Lee, Vicky T. Y.; Sze, Po P.; Rajwani, Rahim; Fung, Kitty S. C.; To, Wing K.; Lee, Rodney A.; Tsang, Dominic N. C.; Siu, Gilman K. H.

2018-01-01

Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module. The results and turnaround times were compared with those of routine microbiological processing. All strains were also characterized by beta-lactamase PCR and sequencing. Results: Using the saponin-based extraction method, MALDI-TOF MS correctly identified bacteria in 116/134 (86.6%) monomicrobial BCs. The detection sensitivities for β-lactamase activities against ampicillin, piperacillin, third-generation cephalosporin and meropenem were 91.3, 100, 97.9, and 100% for cultured isolates, and 80.4, 100, 68.8, and 40% for monomicrobial BCs (n = 134) respectively. The overall specificities ranged from 91.5 to 100%. Furthermore, the MBT STAR-BL and conventional drug susceptibility test results were concordant in 14/19 (73.7%) polymicrobial cultures. Reducing the logRQ cut-off value from 0.4 to 0.2 increased the direct detection sensitivities for β-lactamase activities against ampicillin, cefotaxime and meropenem in BCs to 85.7, 87.5, and 100% respectively. The MBT STAR-BL test enabled the reporting of β-lactamase-producing GNR at 14.16 and 47.64 h before the interim and final reports of routine BCs processing, respectively, were available. Conclusion: The MALDI Biotyper system equipped with the MBT STAR-BL module enables the simultaneous rapid identification of bacterial species and β-lactamase-mediated resistance from BCs and cultured isolates. Adjustment of the logRQ cut-off value to 0.2 significantly increased the detection sensitivities for clinically important drug-resistant pathogens. PMID:29527202

Sibling rivalry: competition between MHC class II family members inhibits immunity.

PubMed

Denzin, Lisa K; Cresswell, Peter

2013-01-01

Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes.

PubMed

Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

2012-11-01

Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role. To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. No significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as 'solubility limited' displayed an overall reduction as compared with 'freely soluble' compounds, as well as an unaltered and increased ppR. Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Implementation of Slag Stabilized Blended Calcium Sulfate (BCS) in a Pavement Structure : Research Project Capsule

DOT National Transportation Integrated Search

2012-09-01

Blended calcium sulfate (BCS) is fl uorogypsum (FG), an industrial byproduct, : blended with lime or limestone. Approximately 90,000 metric tons (100,000 : tons) of FG are generated annually in the United States, posing a serious : problem for enviro...

25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.9 What are the minimum technical standards for Class II gaming system... digits to accommodate the design of the game. (3) Accounting data displayed to the player may be... audit, configuration, recall and test modes; or (ii) Temporarily, during entertaining displays of game...

25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.9 What are the minimum technical standards for Class II gaming system... digits to accommodate the design of the game. (3) Accounting data displayed to the player may be... audit, configuration, recall and test modes; or (ii) Temporarily, during entertaining displays of game...

25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.9 What are the minimum technical standards for Class II gaming system... digits to accommodate the design of the game. (3) Accounting data displayed to the player may be... audit, configuration, recall and test modes; or (ii) Temporarily, during entertaining displays of game...

[Accelerated partial breast irradiation with image-guided intensity-modulated radiotherapy following breast-conserving surgery - preliminary results of a phase II clinical study].

PubMed

Mészáros, Norbert; Major, Tibor; Stelczer, Gábor; Zaka, Zoltán; Mózsa, Emõke; Fodor, János; Polgár, Csaba

2015-06-01

The purpose of the study was to implement accelerated partial breast irradiation (APBI) by means of image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS) for low-risk early invasive breast cancer. Between July 2011 and March 2014, 60 patients with low-risk early invasive (St I-II) breast cancer who underwent BCS were enrolled in our phase II prospective study. Postoperative APBI was given by means of step and shoot IG-IMRT using 4 to 5 fields to a total dose of 36.9 Gy (9×4.1 Gy) using a twice-a-day fractionation. Before each fraction, series of CT images were taken from the region of the target volume using a kV CT on-rail mounted in the treatment room. An image fusion software was used for automatic image registration of the planning and verification CT images. Patient set-up errors were detected in three directions (LAT, LONG, VERT), and inaccuracies were adjusted by automatic movements of the treatment table. Breast cancer related events, acute and late toxicities, and cosmetic results were registered and analysed. At a median follow-up of 24 months (range 12-44) neither locoregional nor distant failure was observed. Grade 1 (G1), G2 erythema, G1 oedema, and G1 and G2 pain occurred in 21 (35%), 2 (3.3%), 23 (38.3%), 6 (10%) and 2 (3.3%) patients, respectively. No G3-4 acute side effects were detected. Among late radiation side effects G1 pigmentation, G1 fibrosis, and G1 fat necrosis occurred in 5 (8.3%), 7 (11.7%), and 2 (3.3%) patients, respectively. No ≥G2 late toxicity was detected. Excellent and good cosmetic outcome was detected in 45 (75%) and 15 (25%) patients. IG-IMRT is a reproducible and feasible technique for the delivery of APBI following conservative surgery for the treatment of low-risk, early-stage invasive breast carcinoma. Preliminary results are promising, early radiation side effects are minimal, and cosmetic results are excellent.

Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated with high body condition scores and elevated serum insulin and leptin.

PubMed

Morfeld, Kari A; Brown, Janine L

2016-04-01

The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world's largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n=23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1=thinnest, 5=fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G:I ratio than cycling BCS 5 females. Using 'non-cycling' as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status.

Sodium bicarbonate secretion indicated by ultrastructural cytochemical localization of HCO3(-), Cl-, and Na+ ions on rat bile duct brush cells.

PubMed

Ogata, Takuro

2005-12-01

Brush cells are widely distributed in the digestive and respiratory apparatus, but their function is still unknown. Because brush cells (BC) are found in organs secreting NaHCO3, it was hypothesized that these cells may secrete NaHCO3. To test this possibility, rat common bile duct epithelia were examined by ultrastructural cytochemical methods for localizing HCO3(-), Cl-, and Na+ ions. All three ion precipitates were few in or on BCs of rats without stimulation. Lead carbonate precipitates, which localized HCO3(-) ions by the lead nitrate-osmium method, increased markedly on the surface of the microvilli (MV) of BCs after secretin or meal stimulation, but similar precipitates were few on the luminal surface of principal cells (PCs). Silver chloride precipitates, which indicate the presence of Cl- ions by the silver-osmium method, increased in the apical cytoplasm and in MV of BCs after secretin or meal stimulation, but they were few in PCs. Sodium pyroantimonate precipitates, which localize Na+ ions by the potassium pyroantimonate-osmium method, increased on the surface of the MV, along the basolateral membrane, and in the apical cytoplasm of BCs after secretin or meal stimulation, but they were few in PCs. These results strongly suggest that BCs may be a significant source of NaHCO3 secretion.

Influence of dental correction on nociceptive test responses, fecal appearance, body condition score, and apparent digestibility coefficient for dry matter of Zamorano-leones donkeys (Equus asinus).

PubMed

Rodrigues, J B; Ferreira, L M; Bastos, E; San Roman, F; Viegas, C; Santos, A S

2013-10-01

The influence of dental correction on nociceptive (pressure) test responses, fecal appearance, BCS, and apparent digestibility coefficient for DM was studied in 18 Zamorano-Leonés donkeys, an endangered local breed from the Zamora province in Spain. For this purpose, donkeys were divided into 2 homogeneous control and treatment groups, based on age, BCS, and dental findings. On d 1, 45, 90, and 135, BCS and nociceptive test responses were evaluated in all donkeys. Feed and fecal samples were collected from all donkeys for 3 consecutive days, starting at each of the aforementioned days. Apparent digestibility coefficient for DM was estimated, using ADL as an internal marker. A progressive decrease of positive nociceptive test responses was observed from d 1 up to 90 (P < 0.01) in the treatment group. No difference between groups was observed for BCS. However, BCS at d 90 was greater (P = 0.018) than observed on d 1 or 45, indicating a time influence. Concerning apparent digestibility coefficient for DM, there were differences among collection days in apparent digestibility coefficient for DM (P < 0.05). No differences in fecal appearance were observed between treatments or collection days. This study highlighted the importance of regular dental care for not only Zamorano-Leonés donkeys but also the equid population, in general, to improve their welfare.

Bipolar cell gap junctions serve major signaling pathways in the human retina.

PubMed

Kántor, Orsolya; Varga, Alexandra; Nitschke, Roland; Naumann, Angela; Énzsöly, Anna; Lukáts, Ákos; Szabó, Arnold; Németh, János; Völgyi, Béla

2017-08-01

Connexin36 (Cx36) constituent gap junctions (GJ) throughout the brain connect neurons into functional syncytia. In the retina they underlie the transmission, averaging and correlation of signals prior conveying visual information to the brain. This is the first study that describes retinal bipolar cell (BC) GJs in the human inner retina, whose function is enigmatic even in the examined animal models. Furthermore, a number of unique features (e.g. fovea, trichromacy, midget system) necessitate a reexamination of the animal model results in the human retina. Well-preserved postmortem human samples of this study are allowed to identify Cx36 expressing BCs neurochemically. Results reveal that both rod and cone pathway interneurons display strong Cx36 expression. Rod BC inputs to AII amacrine cells (AC) appear in juxtaposition to AII GJs, thus suggesting a strategic AII cell targeting by rod BCs. Cone BCs serving midget, parasol or koniocellular signaling pathways display a wealth of Cx36 expression to form homologously coupled arrays. In addition, they also establish heterologous GJ contacts to serve an exchange of information between parallel signaling streams. Interestingly, a prominent Cx36 expression was exhibited by midget system BCs that appear to maintain intimate contacts with bistratified BCs serving other pathways. These findings suggest that BC GJs in parallel signaling streams serve both an intra- and inter-pathway exchange of signals in the human retina.

Finishing occlusion in Class II or Class III molar relation: therapeutic Class II and III.

PubMed

Nangia, A; Darendeliler, M A

2001-11-01

The most frequent extraction regime consists of the removal of upper and lower premolars. Depending on anchorage requirements, camouflage treatment options, surgical intervention, or the absence of teeth in only one arch, it may become necessary to finalize the occlusion with a one-dental-unit discrepancy between the upper and lower dental arches. Guidelines are presented for finishing occlusions in Class II or Class III molar relation.

Evolution and Distribution of Class II-Related Endogenous Retroviruses†

PubMed Central

Gifford, Robert; Kabat, Peter; Martin, Joanne; Lynch, Clare; Tristem, Michael

2005-01-01

Endogenous retroviruses (ERVs) are widespread in vertebrate genomes and have been loosely grouped into “classes” on the basis of their phylogenetic relatedness to the established genera of exogenous retroviruses. Four of these genera—the lentiviruses, alpharetroviruses, betaretroviruses, and deltaretroviruses—form a well-supported clade in retroviral phylogenies, and ERVs that group with these genera have been termed class II ERVs. We used PCR amplification and sequencing of retroviral fragments from more than 130 vertebrate taxa to investigate the evolution of the class II retroviruses in detail. We confirm that class II retroviruses are largely confined to mammalian and avian hosts and provide evidence for a major novel group of avian retroviruses, and we identify additional members of both the alpha- and the betaretrovirus genera. Phylogenetic analyses demonstrated that the avian and mammalian viruses form distinct monophyletic groups, implying that interclass transmission has occurred only rarely during the evolution of the class II retroviruses. In contrast to previous reports, the lentiviruses clustered as sister taxa to several endogenous retroviruses derived from rodents and insectivores. This topology was further supported by the shared loss of both the class II PR-Pol frameshift site and the class II retrovirus G-patch domain. PMID:15858031

Implementation of slag stabilized blended calcium sulfate (BCS) in a pavement structure : tech summary.

DOT National Transportation Integrated Search

2014-07-01

This research was the eld implementation follow-up to laboratory research conducted at LTRC. It also met a need of District 61 sta by : allowing an alternative to the removal and replacement of the old, non-standard BCS found on site. : The re...

Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.

PubMed

Ranasinghe, Srinika; Lamothe, Pedro A; Soghoian, Damien Z; Kazer, Samuel W; Cole, Michael B; Shalek, Alex K; Yosef, Nir; Jones, R Brad; Donaghey, Faith; Nwonu, Chioma; Jani, Priya; Clayton, Gina M; Crawford, Frances; White, Janice; Montoya, Alana; Power, Karen; Allen, Todd M; Streeck, Hendrik; Kaufmann, Daniel E; Picker, Louis J; Kappler, John W; Walker, Bruce D

2016-10-18

CD8 + T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8 + T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8 + T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8 + T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8 + T cell responses can exist in a chronic human viral infection, and may contribute to immune control. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Variations in tooth size and arch dimensions in Malay schoolchildren.

PubMed

Hussein, Khalid W; Rajion, Zainul A; Hassan, Rozita; Noor, Siti Noor Fazliah Mohd

2009-11-01

To compare the mesio-distal tooth sizes and dental arch dimensions in Malay boys and girls with Class I, Class II and Class III malocclusions. The dental casts of 150 subjects (78 boys, 72 girls), between 12 and 16 years of age, with Class I, Class II and Class III malocclusions were used. Each group consisted of 50 subjects. An electronic digital caliper was used to measure the mesio-distal tooth sizes of the upper and lower permanent teeth (first molar to first molar), the intercanine and intermolar widths. The arch lengths and arch perimeters were measured with AutoCAD software (Autodesk Inc., San Rafael, CA, U.S.A.). The mesio-distal dimensions of the upper lateral incisors and canines in the Class I malocclusion group were significantly smaller than the corresponding teeth in the Class III and Class II groups, respectively. The lower canines and first molars were significantly smaller in the Class I group than the corresponding teeth in the Class II group. The lower intercanine width was significantly smaller in the Class II group as compared with the Class I group, and the upper intermolar width was significantly larger in Class III group as compared with the Class II group. There were no significant differences in the arch perimeters or arch lengths. The boys had significantly wider teeth than the girls, except for the left lower second premolar. The boys also had larger upper and lower intermolar widths and lower intercanine width than the girls. Small, but statistically significant, differences in tooth sizes are not necessarily accompanied by significant arch width, arch length or arch perimeter differences. Generally, boys have wider teeth, larger lower intercanine width and upper and lower intermolar widths than girls.

77 FR 50760 - Notice and request for comments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... rehabilitation to Class II and Class III railroad infrastructure damaged by hurricanes, floods, and natural... issued by the President ( http://www.fema.gov/news/disasters.fema#sev1 ). Class II and Class III railroad...

Significance of excipients to enhance the bioavailability of poorly water-soluble drugs in oral solid dosage forms: A Review

NASA Astrophysics Data System (ADS)

Vadlamudi, Manoj Kumar; Dhanaraj, Sangeetha

2017-11-01

Nowadays most of the drug substances are coming into the innovation pipeline with poor water solubility. Here, the influence of excipients will play a significant role to improve the dissolution of poorly aqueous soluble compounds. The drug substance needs to be dissolved in gastric fluids to get the better absorption and bioavailability of an orally administered drug. Dissolution is the rate-controlling stage for drugs which controls the rate and degree of absorption. Usually, poorly soluble oral administrated drugs show a slower dissolution rate, inconsistent and incomplete absorption which can lead to lower bioavailability. The low aqueous solubility of BCS class II and IV drugs is a major challenge in the drug development and delivery process. Several technologies have been used in an attempt to progress the bioavailability of poorly water-soluble drug compounds which include solid dispersions, lipid-based formulations, micronization, solvent evaporation, co-precipitation, ordered mixing, liquid-solid compacts, solvent deposition inclusion complexation, and steam aided granulation. In fact, most of the technologies require excipient as a carrier which plays a significant role in improving the bioavailability using Hypromellose acetate succinate, Cyclodextrin, Povidone, Copovidone, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Crospovidone, Starch, Dimethylacetamide, Polyethylene glycol, Sodium lauryl sulfate, Polysorbate, Poloxamer. Mesoporous silica and so on. This review deliberates about the excipients significance on bioavailability enhancement of drug products in a single platform along with pragmatically proved applications so that user can able to select the right excipients as per the molecule.

MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

PubMed

Dahan, Arik; Amidon, Gordon L

2010-02-15

We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

Pharmaceutical Applications of Relaxation Filter-Selective Signal Excitation Methods for ¹⁹F Solid-State Nuclear Magnetic Resonance: Case Study With Atorvastatin in Dosage Formulation.

PubMed

Asada, Mamiko Nasu; Nemoto, Takayuki; Mimura, Hisashi

2016-03-01

We recently developed several new relaxation filter-selective signal excitation (RFS) methods for (13)C solid-state nuclear magnetic resonance (NMR) that allow (13)C signal extraction of the target components from pharmaceuticals. These methods were successful in not only qualification but also quantitation over the wide range of 5% to 100%. Here, we aimed to improve the sensitivity of these methods and initially applied them to (19)F solid-state NMR, on the basis that the fluorine atom is one of the most sensitive NMR-active nuclei. For testing, we selected atorvastatin calcium (ATC), an antilipid BCS class II drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase and is marketed in crystalline and amorphous forms. Tablets were obtained from 2 generic drug suppliers, and the ATC content occurred mainly as an amorphous form. Using the RFS method with (19)F solid-state NMR, we succeeded in qualifying trace amounts (less than 0.5% w/w level) of crystalline phase (Form I) of ATC in the tablets. RFS methods with (19)F solid-state NMR are practical and time efficient and can contribute not only to the study of pharmaceutical drugs, including those with small amounts of a highly potent active ingredient within a formulated product, but also to the study of fluoropolymers in material sciences. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

In-line monitoring of compaction properties on a rotary tablet press during tablet manufacturing of hot-melt extruded amorphous solid dispersions.

PubMed

Grymonpré, W; Verstraete, G; Van Bockstal, P J; Van Renterghem, J; Rombouts, P; De Beer, T; Remon, J P; Vervaet, C

2017-01-30

As the number of applications for polymers in pharmaceutical development is increasing, there is need for fundamental understanding on how such compounds behave during tableting. This research is focussed on the tableting behaviour of amorphous polymers, their solid dispersions and the impact of hot-melt extrusion on the compaction properties of these materials. Soluplus, Kollidon VA 64 and Eudragit EPO were selected as amorphous polymers since these are widely studied carriers for solid dispersions, while Celecoxib was chosen as BCS class II model drug. Neat polymers and physical mixtures (up to 35% drug load) were processed by hot-melt extrusion (HME), milled and sieved to obtain powders with comparable particle sizes as the neat polymer. A novel approach was used for in-line analysis of the compaction properties on a rotary tablet press (Modul P, GEA) using complementary sensors and software (CDAAS, GEA). By combining 'in-die' and 'out-of-die' techniques, it was possible to investigate in a comprehensive way the impact of HME on the tableting behaviour of amorphous polymers and their formulations. The formation of stable glassy solutions altered the formulations towards more fragmentary behaviour under compression which was beneficial for the tabletability. Principal component analysis (PCA) was applied to summarize the behaviour during compaction of the formulations, enabling the selection of Soluplus and Kollidon VA 64 as the most favourable polymers for compaction of glassy solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

Precipitation-lyophilization-homogenization (PLH) for preparation of clarithromycin nanocrystals: influencing factors on physicochemical properties and stability.

PubMed

Morakul, Boontida; Suksiriworapong, Jiraphong; Leanpolchareanchai, Jiraporn; Junyaprasert, Varaporn Buraphacheep

2013-11-30

Nanocrystals is one of effective technologies used to improve solubility and dissolution behavior of poorly soluble drugs. Clarithromycin is classified in BCS class II having low bioavailability due to very low dissolution behavior. The main purpose of this study was to investigate an efficiency of clarithromycin nanocrystals preparation by precipitation-lyophilization-homogenization (PLH) combination method in comparison with high pressure homogenization (HPH) method. The factors influencing particle size reduction and physical stability were assessed. The results showed that the PLH technique provided an effective and rapid reduction of particle size of nanocrystals to 460 ± 10 nm with homogeneity size distribution after only the fifth cycle of homogenization, whereas the same size was attained after 30 cycles by the HPH method. The smallest nanocrystals were achieved by using the combination of poloxamer 407 (2%, w/v) and SLS (0.1%, w/v) as stabilizers. This combination could prevent the particle aggregation over 3-month storage at 4 °C. The results from SEM showed that the clarithromycin nanocrystals were in cubic-shaped similar to its initial particle morphology. The DSC thermogram and X-ray diffraction pattern of nanocrystals were not different from the original drug except for intensity of peaks which indicated the presenting of nanocrystals in the crystalline state and/or partial amorphous form. In addition, the dissolution of the clarithromycin nanocrystals was dramatically increased as compared to the coarse clarithromycin. Copyright © 2013 Elsevier B.V. All rights reserved.

Spontaneously self-assembled micelles from poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-trimethylene carbonate) for drug solubilization.

PubMed

Latere, Dwan'Isa J P; Rouxhet, L; Brewster, M E; Préat, V; Ariën, A

2008-03-01

Di-block copolymers composed of polyethylene glycol (PEG) and a second block of (co)polyesters of epsilon-caprolactone (CL) and/or trimethylene carbonate (TMC) were synthesized and characterized. Tin octoate was used as catalyst and polymerization were completed over a period of 24 h with high conversion (> 95%). Self-assembling properties in water were evaluated. All di-block copolymers behave similarly except when PCL served as the second block. Stable crew-cut micelles of about 20 nm were obtained by direct dissolution of the liquid di-block copolymers in water at room temperature. When PCL was present as the second block, no solubilization occurred. Drug encapsulation of poorly water-soluble drugs belonging to biopharmaceutics classification system (BCS) class II (ketoprofen and furosemide) was evaluated. Experimental solubility for these two drugs shows a significant enhancement such that a maximum value of 23.4 mg/ml was obtained for ketoprofen in a 10% w/v micellar solution as compared to 0.14 mg in water. In the case of furosemide, the solubility increased from 0.04 mg/ml in water to about 3.2 mg/ml in a 10% w/v micellar solution. Enzymatic degradation of diblock copolymers was also studied in the presence of Pseudomonas lipase in a phosphate buffer solution (pH 7.4). Results indicated rapid degradation of copolymers containing relatively higher amounts of CL compared to TMC suggesting the potential in vivo degradation.

Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential.

PubMed

Singh, Bhupinder; Khurana, Lalit; Bandyopadhyay, Shantanu; Kapil, Rishi; Katare, O O P

2011-11-01

Carvedilol, a widely prescribed cardiovascular drug for hypertension and congestive heart failure, exhibits low and variable bioavailability owing to poor absorption and extensive hepatic first-pass metabolism. The current research work, therefore, entails formulation development of liquid self-nano-emulsifying drug delivery systems (SNEDDS) to enhance the bioavailability of carvedilol by facilitating its transport via lymphatic circulation. The formulation constituents, i.e. lipids, surfactants, and co-surfactants, were selected on the basis of solubility studies. Pseudo-ternary phase diagrams were constructed to embark upon the selection of blend of lipidic (i.e. Capmul PG8) and hydrophilic components (i.e. Cremophor EL as surfactant and Transcutol HP as co-surfactant) for efficient and robust formulation of SNEDDS. The SNEDDS, systematically optimized employing a central composite design (CCD), were evaluated for various response variables viz drug release parameters, emulsification time, emulsion droplet size, and mean dissolution time. In vitro drug release studies depicted that the release from SNEDDS systems followed a non-Fickian kinetic behavior. The TEM imaging of the optimized formulation affirmed the uniform shape and nano size of the system. Accelerated studies of the optimized formulation indicated high stability of the formulation for 6 months. The in situ perfusion studies carried out in wistar rats construed several fold augmentation in the permeability and absorption potential of the optimized formulation vis-à-vis marketed formulation. Thus, the present studies ratified the potential of SNEDDS in augmenting the oral bioavailability of BCS class II drugs.

Development Considerations for Nanocrystal Drug Products.

PubMed

Chen, Mei-Ling; John, Mathew; Lee, Sau L; Tyner, Katherine M

2017-05-01

Nanocrystal technology has emerged as a valuable tool for facilitating the delivery of poorly water-soluble active pharmaceutical ingredients (APIs) and enhancing API bioavailability. To date, the US Food and Drug Administration (FDA) has received over 80 applications for drug products containing nanocrystals. These products can be delivered by different routes of administration and are used in a variety of therapeutic areas. To aid in identifying key developmental considerations for these products, a retrospective analysis was performed on the submissions received by the FDA to date. Over 60% of the submissions were for the oral route of administration. Based on the Biopharmaceutics Classification System (BCS), most nanocrystal drugs submitted to the FDA are class II compounds that possess low aqueous solubility and high intestinal permeability. Impact of food on drug bioavailability was reduced for most nanocrystal formulations as compared with their micronized counterparts. For all routes of administration, dose proportionality was observed for some, but not all, nanocrystal products. Particular emphasis in the development of nanocrystal products was placed on the in-process tests and controls at critical manufacturing steps (such as milling process), mitigation and control of process-related impurities, and the stability of APIs or polymorphic form (s) during manufacturing and upon storage. This emphasis resulted in identifying challenges to the development of these products including accurate determination of particle size (distribution) of drug substance and/or nanocrystal colloidal dispersion, identification of polymorphic form (s), and establishment of drug substance/product specifications.

Can crystal engineering be as beneficial as micronisation and overcome its pitfalls?: A case study with cilostazol.

PubMed

Sai Gouthami, Kodukula; Kumar, Dinesh; Thipparaboina, Rajesh; Chavan, Rahul B; Shastri, Nalini R

2015-08-01

Improvement in dissolution of the drugs having poor solubility is a challenge in pharmaceutical industry. Micronization is one technique, employed for dissolution enhancement of cilostazol, a BCS class II drug. However, the obtained micronized drug possesses poor flowability. The aim of this study was to improve the dissolution rate and flow properties of cilostazol by crystal engineering, using habit modification method and compare with micronized cilostazol bulk drug. Simulation studies were performed to predict the effect of solvents on cilostazol crystal habit. Cilostazol crystals with different habits were prepared by solvent:anti-solvent crystallization technique. SEM, FTIR, DSC, TGA and PXRD were used for solid state characterization. The results revealed that cilostazol re-crystallized from methanol-hexane system were hexagonal and ethanol-hexane system gave rods. Cilostazol engineered habits showed increased dissolution rate than unprocessed drug but similar dissolution rate when compared to micronized cilostazol. Micronized cilostazol showed a dissolution efficiency of 75.58% where as cilostazol recrystallized from methanol-hexane and ethanol-hexane systems resulted in a dissolution efficiency of 72.63% and 68.63%, respectively. In addition, crystal engineering resulted in improved flow properties of re-crystallized habits when compared to micronized form of the drug. In conclusion, crystal engineering by habit modification show potential for dissolution enhancement with an added advantage of improved flow properties over micronization technique, for poorly soluble drugs like cilostazol. Copyright © 2015 Elsevier B.V. All rights reserved.

Quality-by-design case study: investigation of the role of poloxamer in immediate-release tablets by experimental design and multivariate data analysis.

PubMed

Kaul, Goldi; Huang, Jun; Chatlapalli, Ramarao; Ghosh, Krishnendu; Nagi, Arwinder

2011-12-01

The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed. Poloxamer was found to increase dissolution rates in granules as expected of surfactants in general but retard dissolution in tablets. The unexpected effect of poloxamer in tablets was accompanied by an increase in tablet-disintegration-time-mediated slowdown of tablet dissolution and by a surrogate binding effect of poloxamer at higher concentrations. It was additionally realized through MVDA that poloxamer in tablets either acts as a binder by itself or promotes binder action of the binder povidone resulting in increased intragranular cohesion. Additionally, poloxamer was found to mediate tablet dissolution on stability as well. In contrast to tablet dissolution at release (time zero), poloxamer appeared to increase tablet dissolution in a concentration-dependent manner on accelerated open-dish stability. Substituting polysorbate 80 as an alternate surfactant in place of poloxamer in the formulation was found to stabilize tablet dissolution.

Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization.

PubMed

Marano, Stefania; Barker, Susan A; Raimi-Abraham, Bahijja T; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Aliev, Abil E; Craig, Duncan Q M

2017-05-01

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.

Strategies to gain body condition score in pasture-based dairy cows during late lactation and the far-off nonlactating period and their interaction with close-up dry matter intake.

PubMed

Roche, J R; Heiser, A; Mitchell, M D; Crookenden, M A; Walker, C G; Kay, J K; Riboni, M Vailati; Loor, J J; Meier, S

2017-03-01

In pasture-based systems, cows are generally thinner at the end of lactation than cows fed total mixed rations and, as a result, over-feeding of metabolizable energy (ME) during the far-off nonlactating period is a standard management policy to achieve optimum calving body condition score (BCS). An alternative would be to manage cows to gain BCS through late lactation, such that cows ended lactation close to optimum calving BCS and maintenance of BCS through to calving. We sought to quantify the effect of moderate or excessive ME intakes during the far-off nonlactating period in cows that had been managed to gain or maintain BCS through late lactation and whether the far-off management strategy interacted with close-up level of feeding. Effects on milk production and circulating indicators of energy balance and metabolic health in early lactation were evaluated. A herd of 150 cows was randomly assigned to 1 of 2 feeding levels in late lactation to achieve a low and high BCS at the time of dry-off (approximately 4.25 and 5.0 on a 10-point scale). Following dry-off, both herds were managed to achieve a BCS of 5.0 one month before calving; this involved controlled feeding (i.e., maintenance) and over-feeding of ME during the far-off dry period. Within each far-off feeding-level treatment, cows were offered 65, 90, or 120% of their pre-calving ME requirements for 3 wk pre-calving in a 2 × 3 factorial arrangement (i.e., 25 cows/treatment). Body weight and BCS were measured weekly before and after calving, and milk production was measured weekly until wk 7 postcalving. Blood samples were collected weekly for 4 wk pre-calving and 5 wk postcalving, and on d 0, 1, 2, 3, and 4 relative to calving, and analyzed for indicators of energy balance (e.g., blood fatty acids, β-hydroxybutyrate), calcium status, and inflammatory state. No interaction was observed between far-off and close-up feeding levels. Over-feeding of ME to low BCS cows during the far-off nonlactating period reduced blood fatty acid and β-hydroxybutyrate concentrations in early lactation, and increased blood albumin to globulin ratio compared with cows that were dried off close to recommended calving BCS and control-fed during the far-off dry period. Cows consuming 65% of their ME requirements during the close-up period had lower fatty acids and β-hydroxybutyrate in early lactation, but produced less milk, particularly during the first 21 d of lactation, had more than 3-fold greater concentration of haptoglobin immediately postcalving, and had a lower blood cholesterol concentration and albumin to globulin ratio, when compared with cows offered 90 or 120% of their ME requirements. Collectively, these measurements indicate that a severe restriction (<70% of ME requirements) during the close-up nonlactating period increases the risk of disease in early lactation and reduces milk production. In summary, far-off over-feeding of ME to cows that needed to gain BCS did not influence peripartum metabolic health in grazing dairy cows, but restricting cows below 70% ME requirements during the close-up transition period resulted in a blood profile indicative of greater inflammation. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Polymorphism at Expressed DQ and DR Loci in Five Common Equine MHC Haplotypes

PubMed Central

Miller, Donald; Tallmadge, Rebecca L.; Binns, Matthew; Zhu, Baoli; Mohamoud, Yasmin Ali; Ahmed, Ayeda; Brooks, Samantha A.; Antczak, Douglas F.

2016-01-01

The polymorphism of Major Histocompatibility Complex (MHC) class II DQ and DR genes in five common Equine Leukocyte Antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine Bacterial Artificial Chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next Generation Sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse. PMID:27889800

40 CFR 82.23 - Transfers of allowances of class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., any production, and allowable imports and exports of class II controlled substances reported by the... quantity of the transferor's class II consumption allowances, production allowances, export production... EPA; and (G) For trades of consumption allowances, production allowances, export production allowances...

Interaction of Mycobacterium avium-containing phagosomes with the antigen presentation pathway.

PubMed

Ullrich, H J; Beatty, W L; Russell, D G

2000-12-01

Pathogenic mycobacteria infect macrophages where they replicate in phagosomes that minimize contact with late endosomal/lysosomal compartments. Loading of Ags to MHC class II molecules occurs in specialized compartments with late endosomal characteristics. This points to a sequestration of mycobacteria-containing phagosomes from the sites where Ags meet MHC class II molecules. Indeed, in resting macrophages MHC class II levels decreased strongly in phagosomes containing M. avium during a 4-day infection. Phagosomal MHC class II of early (4 h) infections was partly surface-derived and associated with peptide. Activation of host macrophages led to the appearance of H2-M, a chaperon of Ag loading, and to a strong increase in MHC class II molecules in phagosomes of acute (1 day) infections. Comparison with the kinetics of MHC class II acquisition by IgG-coated bead-containing phagosomes suggests that the arrest in phagosome maturation by mycobacteria limits the intersection of mycobacteria-containing phagosomes with the intracellular trafficking pathways of Ag-presenting molecules.

Bone-anchored intermaxillary elastics in an asymmetric Class II malocclusion: A case report.

PubMed

Manni, Antonio; Lupini, Daniela; Cozzani, Mauro

2017-06-01

A 13-year-old male patient, presenting a Class II, division 1 malocclusion and crowding was treated by an innovative technique. After rapid palatal expansion by a Hyrax appliance, the teeth were bonded with straightwire brackets. Two miniscrews were inserted, one per side, in the mandibular buccal bone between the roots of the mandibular first molar and the second premolar. On the right side, the miniscrew implant was connected to the hook clamped on a 0.021×0.028″ SS wire with a twisted SS ligature in order to maintain the inclination of the frontal incisors during the Class II mechanics. On the left side, where the Class II relationship was more marked, intermaxillary elastics were applied from the upper left hook clamped on the archwire to the lower first molar and a power chain (100g) was stretched from the lower left hook to the miniscrew implant. Class II correction was accomplished using sequential Class II elastics of progressive strength coupled with rectangular stainless steel wires. After 22 months of active treatment, the results were balanced facial esthetics and a good occlusion. This dual anchorage set-up of Class II elastics reinforced with TADs produced protrusive action on the mandible with minimal side effects and with no significant change in the vertical dimension during the sagittal correction of the Class II malocclusion. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

Anteroposterior condylar position: a comparative study between subjects with normal occlusion and patients with Class I, Class II Division 1, and Class III malocclusions.

PubMed

Fraga, Marcelo Reis; Rodrigues, Andréia Fialho; Ribeiro, Luiz Claudio; Campos, Marcio José da Silva; Vitral, Robert Willer Farinazzo

2013-10-29

The present study aimed to determine and compare the anteroposterior position of the condyle in the mandibular fossa between groups of asymptomatic subjects with normal occlusion and asymptomatic subjects with Class I, Class II Division 1, and Class III malocclusions. Thirty persons with normal occlusion, 30 with Class I malocclusion, 30 with Class II Division 1, and 30 with Class III had computed tomography scans of their temporomandibular joints. The anterior joint space/posterior joint space (AJS/PJS) ratio was determined for the right and left joints. The paired t test was used to analyze the AJS/PJS ratio between both sides for each group. The ANOVA test was applied to verify the differences between the groups for the measurements of the right and left sides. In case the ANOVA test confirmed significance, the Dunnett's t test was performed to compare the groups of malocclusion with that of normal occlusion. The paired t test between the AJS/PJS relationships in the right and left sides showed the following p values: Class I (0.168), Class II Division 1 (0.662), Class III (0.991), and normal occlusion (0.390). The ANOVA test showed a p value of 0.445 for the comparisons of the right side and 0.040 for the left side. The Dunnett's t test demonstrated a statistically significant difference between the Class II group and the normal occlusion group (p value of 0.026) in the joints of the left side. Bilateral symmetry and lack of condyle centralization were common characteristics among all groups. The greatest condylar decentralization was observed in the Class II group, whereas the least condylar decentralization was found in the normal occlusion group.

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant.

PubMed

Kamburova, E G; Wisse, B W; Joosten, I; Allebes, W A; van der Meer, A; Hilbrands, L B; Baas, M C; Spierings, E; Hack, C E; van Reekum, F E; van Zuilen, A D; Verhaar, M C; Bots, M L; Drop, A C A D; Plaisier, L; Seelen, M A J; Sanders, J S F; Hepkema, B G; Lambeck, A J A; Bungener, L B; Roozendaal, C; Tilanus, M G J; Voorter, C E; Wieten, L; van Duijnhoven, E M; Gelens, M; Christiaans, M H L; van Ittersum, F J; Nurmohamed, S A; Lardy, N M; Swelsen, W; van der Pant, K A; van der Weerd, N C; Ten Berge, I J M; Bemelman, F J; Hoitsma, A; van der Boog, P J M; de Fijter, J W; Betjes, M G H; Heidt, S; Roelen, D L; Claas, F H; Otten, H G

2018-02-21

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence. © 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

What is strange about high-temperature superconductivity in cuprates?

NASA Astrophysics Data System (ADS)

Božović, I.; He, X.; Wu, J.; Bollinger, A. T.

2017-10-01

Cuprate superconductors exhibit many features, but the ultimate question is why the critical temperature (Tc) is so high. The fundamental dichotomy is between the weak-pairing, Bardeen-Cooper-Schrieffer (BCS) scenario, and Bose-Einstein condensation (BEC) of strongly-bound pairs. While for underdoped cuprates it is hotly debated which of these pictures is appropriate, it is commonly believed that on the overdoped side strongly-correlated fermion physics evolves smoothly into the conventional BCS behavior. Here, we test this dogma by studying the dependence of key superconducting parameters on doping, temperature, and external fields, in thousands of cuprate samples. The findings do not conform to BCS predictions anywhere in the phase diagram.

Comparison of BMI, AHI, and apolipoprotein E ε4 (APOE-ε4) alleles among sleep apnea patients with different skeletal classifications.

PubMed

Roedig, Jason J; Phillips, Barbara A; Morford, Lorri A; Van Sickels, Joseph E; Falcao-Alencar, Gabriel; Fardo, David W; Hartsfield, James K; Ding, Xiuhua; Kluemper, G Thomas

2014-04-15

This case-control study investigated whether variations within the APOE-ε gene were associated with having a convex facial profile (skeletal Class II) compared to exhibiting a straight or concave facial profile (Class I or Class III) among patients with obstructive sleep apnea (OSA). Associations between the apnea-hypopnea index (AHI) and body mass index (BMI) scores for these OSA patients were also examined in the context of facial profile. OSA patients with an AHI ≥ 15 were recruited from a sleep clinic and classified by facial and dental occlusal relationships based on a profile facial analysis, lateral photographs, and dental examination. Saliva was collected as a source of DNA. The APOE-ε1-4 allele-defining single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped. A χ(2) analysis was used to assess Hardy-Weinberg equilibrium and for association analysis (significance at p < 0.05). ANOVA and Fisher exact test were also used. Seventy-six Caucasian OSA patients participated in the study-25 Class II cases and 51 non-Class II cases. There was no association of the APOE-ε4 allele with facial profile among these OSA patients. Class II OSA patients had significantly lower BMIs (30.7 ± 5.78) than Class I (37.3 ± 6.14) or Class III (37.8 ± 6.17) patients (p < 0.001), although there was no statistical difference in AHI for Class II patients compared with other groups. OSA patients with Class II convex profile were more likely to have a lower BMI than those in other skeletal groups. In fact 20% of them were not obese, suggesting that a Class II convex profile may influence or be associated with OSA development independent of BMI.

A cephalometric analysis of Class II dentate subjects to establish a formula to determine the occlusal plane in Class II edentate subjects: A neo adjunct.

PubMed

Sinha, Nikita; Reddy, K Mahendranadh; Gupta, Nidhi; Shastry, Y M

2017-01-01

Occlusal plane (OP) differs considerably in participants with skeletal Class I and Class II participants. In this study, cephalometrics has been used to help in the determination of orientation of the OP utilizing the nonresorbable bony anatomic landmarks in skeletal Class II participants and an attempt has been made to predict and examine the OP in individuals with skeletal class II jaw relationship. One hundred dentulous participants with skeletal Class II malocclusion who came to the hospital for correcting their jaw relationship participated in the study. Their right lateral cephalogram was taken using standardized procedures, and all the tracings were manually done by a single trained examiner. The cephalograms which were taken for the diagnostic purpose were utilized for the study, and the patient was not exposed to any unnecessary radiation. The numerical values obtained from the cephalograms were subjected to statistical analysis. Pearson's correlation of <0.001 was considered significant, and a linear regression analysis was performed to determine a formula which would help in the determination of orientation of the OP in Class II edentulous participants. Pearson's correlation coefficient and linear regression analysis were performed, and a high correlation was found between A2 and (A2 + B2)/(B2 + C2) with " r " value of 0.5. A medium correlation was found between D2 and (D2 + E2)/(E2 + F2) with " r " value of 0.42. The formula obtained for posterior reference frame through linear regression equation was y = 0.018* × +0.459 and the formula obtained for anterior reference frame was y1 = 0.011* × 1 + 0.497. It was hypothesized that by substituting these formulae in the cephalogram obtained from the Class II edentate individual, the OP can be obtained and verified. It was concluded that cephalometrics can be useful in examining the orientation of OP in skeletal Class II participants.

77 FR 32465 - Technical Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... minimum odds for Class II games; amend standards for test labs; remove references to the Federal... the Play of Class II Games. 73 FR 60508. The rule added a new part to the Commission's regulations establishing a process for ensuring the integrity of electronic Class II games and aids. The standards were...

40 CFR 147.1600 - State-administered program-Class II wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New...

40 CFR 144.22 - Existing Class II enhanced recovery and hydrocarbon storage wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and hydrocarbon storage wells. 144.22 Section 144.22 Protection of Environment ENVIRONMENTAL... of Underground Injection by Rule § 144.22 Existing Class II enhanced recovery and hydrocarbon storage wells. (a) An existing Class II enhanced recovery or hydrocarbon storage injection well is authorized by...

40 CFR 144.22 - Existing Class II enhanced recovery and hydrocarbon storage wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and hydrocarbon storage wells. 144.22 Section 144.22 Protection of Environment ENVIRONMENTAL... of Underground Injection by Rule § 144.22 Existing Class II enhanced recovery and hydrocarbon storage wells. (a) An existing Class II enhanced recovery or hydrocarbon storage injection well is authorized by...

40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... kilograms) of production of each class II controlled substance used in processes resulting in their...) The quantity (in kilograms) of production of each class II controlled substance used in processes... processes resulting in their transformation or eventual destruction; (vi) A list of the quantities and names...

Effect of immunodepletion of MHC class II-positive cells from pancreatic islets on generation of cytotoxic T-lymphocytes in mixed islet-lymphocyte coculture.

PubMed

Stock, P G; Ascher, N L; Platt, J L; Kaufman, D B; Chen, S; Field, M J; Sutherland, D E

1989-01-01

In vitro manipulation of pancreatic islets to decrease islet immunogenicity before transplantation has largely been directed at eliminating the major histocompatibility complex (MHC) class II-positive passenger leukocytes from the islets. The mixed islet-lymphocyte coculture (MILC) system was used to quantitate the efficacy of immunodepletion of MHC class II-positive cells from pancreatic islets in terms of reducing immunogenicity. With these experiments we compared the in vitro immunogenicity of MHC class II-depleted islets with untreated islets. B10.BR (H-2k) islets were treated with anti-Iak alloserum followed by complement. This treatment successfully eliminated MHC class II-positive cells from the islets, as demonstrated by indirect immunofluorescence techniques. Depleted islets generated slightly lower amounts of allospecific cytotoxic T-lymphocyte (CTL) activity when exposed to C57BL/6 (H-2b) splenocytes in the MILC than untreated control islets. Although the amount of CTL generated by the depleted islets was slightly less than that generated by untreated islets, there was significant stimulation of CTL by the MHC class II-depleted islets. Therefore, the presence or absence of MHC class II cells within the islet is unlikely to be the decisive factor contributing to islet immunogenicity.

Skeletal effects in Angle Class II/1 patients treated with the functional regulator type II : Cephalometric and tensor analysis.

PubMed

Schulz, Simone; Koos, Bernd; Duske, Kathrin; Stahl, Franka

2016-11-01

The purpose of this work was to employ both cephalometric and tensor analysis in characterizing the skeletal changes experienced by patients with Angle Class II/1 malocclusion during functional orthodontic treatment with the functional regulator type II. A total of 23 patients with Class II/1 malocclusion based on lateral cephalograms obtained before and after treatment with the functional regulator type II were analyzed. Another 23 patients with Angle Class II/1 malocclusion who had not undergone treatment were included as controls. Our cephalometric data attest to significant therapeutic effects of the functional regulator type II on the skeletal mandibular system, including significant advancement of the mandible, increases in effective mandibular length with enhancement of the chin profile, and reduction of growth-related bite deepening. No treatment-related effects were observed at the cranial-base and midface levels. In addition, tensor analysis revealed significant stimulation of mandibular growth in sagittal directions, without indications of growth effects on the maxilla. Its growth-pattern findings differed from those of cephalometric analysis by indicating that the appliance did promote horizontal development, which supports the functional orthodontic treatment effect in Angle Class II/1 cases. Tensor analysis yielded additional insights into sagittal and vertical growth changes not identifiable by strictly cephalometric means. The functional regulator type II was an effective treatment modality for Angle Class II/1 malocclusion and influenced the skeletal development of these patients in favorable ways.

Investigation on etiology of hepatic venous obstruction Budd-Chiari syndrome.

PubMed

Tian, Zhi-Long; Jia, Gao-Lei; Xi, Hai-Lin; Feng, Su; Wang, Xiao-Kai; Li, Rui

2014-12-01

Budd-Chiari syndrome (BCS) is an uncommon clinical condition with a complex etiology. Pathogenesis of BCS is still poorly understood. We included hepatic veno-occlusive lesion tissues of 20 patients (patients group) with hepatic venous obstruction BCS and compared with 20 similar tissues with other etiologies (control group). Morphological changes in hepatic veno-occlusive lesion tissues and the positive expression of proliferating cell nuclear antigen (PCNA), C-myc, and P-53 were observed by the pathological examination (H&E staining) and immunohistochemistry assay. Our results showed that PCNA and C-myc positive cell densities were significantly higher in patient group than control group. P-53 positive cell density showed increasing trends in patients than control group. Moreover, we observed irregular hyperplasia in intimal tissue, fibrous connective tissue, and smooth muscle cell, accompanied by tissue degeneration (hyaloid degeneration and fibrinoid degeneration) and a large quantity of inflammatory cell infiltration. In conclusion, an overexpression of PCNA, C-myc, and a weak positive expression of P53 might launch the extremely irregular hepatic venous intimal hyperplasia, which is probably one of the etiologies of hepatic venous obstruction BCS.

Methods, systems and apparatus for controlling operation of two alternating current (AC) machines

DOEpatents

Gallegos-Lopez, Gabriel [Torrance, CA; Nagashima, James M [Cerritos, CA; Perisic, Milun [Torrance, CA; Hiti, Silva [Redondo Beach, CA

2012-02-14

A system is provided for controlling two AC machines. The system comprises a DC input voltage source that provides a DC input voltage, a voltage boost command control module (VBCCM), a five-phase PWM inverter module coupled to the two AC machines, and a boost converter coupled to the inverter module and the DC input voltage source. The boost converter is designed to supply a new DC input voltage to the inverter module having a value that is greater than or equal to a value of the DC input voltage. The VBCCM generates a boost command signal (BCS) based on modulation indexes from the two AC machines. The BCS controls the boost converter such that the boost converter generates the new DC input voltage in response to the BCS. When the two AC machines require additional voltage that exceeds the DC input voltage required to meet a combined target mechanical power required by the two AC machines, the BCS controls the boost converter to drive the new DC input voltage generated by the boost converter to a value greater than the DC input voltage.

Factors affecting local recurrence and distant metastases of invasive breast cancer after breast-conserving surgery in Chiang Mai University Hospital.

PubMed

Ditsatham, Chagkrit; Somwangprasert, Areewan; Watcharachan, Kirati; Wongmaneerung, Phanchaporn; Khorana, Jiraporn

2016-01-01

The purpose of this study was to collect data regarding breast cancer profiles and factors that affect local recurrence and distant metastasis after breast-conserving surgery (BCS) in Chiang Mai University Hospital. This study was a retrospective review in a single institution of newly diagnosed invasive breast cancer patients who were treated with BCS between April 9, 2001 and December 25, 2011. A total of 185 patients treated with BCS were included in this study, with an average age of 46.83 years. The average recurrence age was 41.1 years and the average nonrecurrence age was 47.48 years, with a recurrence rate of 10.27%. Premenopause was significant in recurrence (P=0.047), as well as non-estrogen-expression patients (P=0.001) and patients who did not receive antihormonal treatment (P=0.011). The recurrence rate in our institute was 10.27%. Factors affecting recurrence after BCS included young age, premenopausal status, nonexpression of the estrogen receptor, and patients who had not received antihormonal treatment. The recurrence rate was higher in the first 90 postoperative months.

Effects of pyrolysis temperature on soybean stover- and peanut shell-derived biochar properties and TCE adsorption in water.

PubMed

Ahmad, Mahtab; Lee, Sang Soo; Dou, Xiaomin; Mohan, Dinesh; Sung, Jwa-Kyung; Yang, Jae E; Ok, Yong Sik

2012-08-01

Conversion of crop residues into biochars (BCs) via pyrolysis is beneficial to environment compared to their direct combustion in agricultural field. Biochars developed from soybean stover at 300 and 700 °C (S-BC300 and S-BC700, respectively) and peanut shells at 300 and 700 °C (P-BC300 and P-BC700, respectively) were used for the removal of trichloroethylene (TCE) from water. Batch adsorption experiments showed that the TCE adsorption was strongly dependent on the BCs properties. Linear relationships were obtained between sorption parameters (K(M) and S(M)) and molar elemental ratios as well as surface area of the BCs. The high adsorption capacity of BCs produced at 700 °C was attributed to their high aromaticity and low polarity. The efficacy of S-BC700 and P-BC700 for removing TCE from water was comparable to that of activated carbon (AC). Pyrolysis temperature influencing the BC properties was a critical factor to assess the removal efficiency of TCE from water. Copyright © 2012 Elsevier Ltd. All rights reserved.

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies.

PubMed

Gangaiah, Dharanesh; Spinola, Stanley M

2016-12-01

Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown. We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree. CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.

Effectiveness of laparoscopic Roux-en-Y gastric bypass on obese class I type 2 diabetes mellitus patients.

PubMed

Xu, Lu; Yin, Jun; Mikami, Dean J; Portenier, Dana D; Zhou, Xiaojun; Mao, Zhongqi

2015-01-01

Laparoscopic Roux-en-Y gastric bypass (LRYGB) can dramatically improve type 2 diabetes mellitus (T2D) in obese class II and III patients. There is increasing evidence that shows bariatric surgery can also ameliorate T2D in patients with BMI between 30 kg/m(2) and 35 kg/m(2) (obese class I). To compare the effectiveness of LRYGB on T2D in obese class I patients with that of obese class II and III T2D patients. University Hospital, China A prospective study was performed in the authors' center from March 2010 to July 2011. Forty-two consecutive obese patients were included in the study. Anthropometric and metabolism parameters were compared between obese class II and III patients and obese class I patients before and after LRYGB. No patients were lost to follow up. After 36 months, metabolic parameters significantly improved in both groups. Partial remission rates between the 2 groups at each time point (12 months, 24 months, and 36 months) were comparable. Obese class II and III patients had higher complete remission rates at 12 months and 24 months, but no difference was observed at 36 months. Both obese class II and III patients and obese class I T2D patients showed significant improvement in multiple parameters after LRYGB. Obese class II and III patients had a higher complete remission rate than obese class I patients. Standardized remission criteria are needed to make outcomes form different centers comparable. Large prospective studies are needed and long-term outcomes have to be observed to better evaluate effectiveness of LRYGB on obese class I T2D patients. Copyright © 2015 American Society for Bariatric Surgery. All rights reserved.

The influence of black carbon on the sorption and desorption of two model PAHs in natural soils.

PubMed

Chi, Fung-Hwa

2014-01-01

Black carbons (BC) which result from the incomplete combustion of farm waste [man-made (burned) BC] are highly absorbent. In Taiwan, the burning of farm waste known as slash and burn is common. The BCs from the burning may present an environmental challenge. Little is known about the effect of BCs on the transport of hydrophobic organic contaminants (HOC). This study investigates the sorption of anthracene and naphthalene to BCs in soil and efficiency of the surfactants Tween 80 and Triton X-100 in their removal. Both surfactants demonstrated 2-6 times increased solubility in the soils with the addiction of BC. Column experiments were performed to imitate the transportation of these contaminants in groundwater through soils before and after adding BC produced by burning farm waste in the lab. We found significantly increased sorption of anthracene in soil added with BCs produced in the lab, suggesting that fraction of organic carbon (foc) can contribute to sorption of such HOCs. Sorption of naphthalene was increased but not significantly. Comparing the concentrations of contaminants, we found the soil containing BC from burned farm waste absorbed HOC more efficiently than the organic BC (naturally-occurring) in the original soil. Therefore, sorption capacity and influence on the transport of HOC cannot be estimated simply by the foc of the soil because the two BCs differ greatly in their sorption ability. BC from farm waste absorbs more contaminants than naturally occurring BC in the soil.

Balloon catheter sinuplasty and adenoidectomy in children with chronic rhinosinusitis.

PubMed

Ramadan, Hassan H; Terrell, Andrew M

2010-09-01

Adenoidectomy is the first step in the surgical management of children with chronic rhinosinusitis (CRS). Adenoidectomy, however, is only effective in half of these children. Although endoscopic sinus surgery is effective for CRS, there is concern for facial growth retardation and major complications. We propose that balloon catheter sinuplasty (BCS) is a minimally invasive, effective procedure in the treatment of pediatric CRS. We undertook a nonrandomized, controlled, prospective review of children with failed medical management of CRS who underwent BCS or adenoidectomy. Outcomes were assessed at 1 year of follow-up and were based on SN-5 scores and the need for revision surgery. Forty-nine children who satisfied the inclusion criteria were reviewed. Thirty of the children had BCS. The age range was 4 to 11 years (mean, 7.7 years), and the mean computed tomography score (Lund-Mackay system) was 7.5. Twenty-four of the 30 patients (80%) who underwent BCS showed improvement of their symptoms after 12 months of follow-up, compared with 10 of the 19 patients (52.6%) who underwent adenoidectomy (p < 0.05). A multivariate analysis using logistic regression analysis with age, sex, asthma, and computed tomography score as covariables showed that BCS was also more effective than adenoidectomy in older children. None of the other variables showed statistical significance. Balloon catheter sinuplasty offers a procedure that is more effective than adenoidectomy and less invasive than endoscopic sinus surgery in the treatment of pediatric CRS.

Are immigrants and nationals born to immigrants at higher risk for delayed or no lifetime breast and cervical cancer screening? The results from a population-based survey in Paris metropolitan area in 2010.

PubMed

Rondet, Claire; Lapostolle, Annabelle; Soler, Marion; Grillo, Francesca; Parizot, Isabelle; Chauvin, Pierre

2014-01-01

This study aims to compare breast cancer screening (BCS) and cervical cancer screening (CCS) practices of French women born to French parents with those of immigrants and nationals born to immigrants, taking their socioeconomic status into account. The study is based on data collected in 2010 in the Paris metropolitan area among a representative sample of 3000 French-speaking adults. For women with no history of breast or cervical cancer, multivariate logistic regressions and structural equation models were used to investigate the factors associated with never having undergone BCS or CCS. We confirmed the existence of a strong gradient, with respect to migration origin, for delaying or never having undergone BCS or CCS. Thus, being a foreign immigrant or being French of immigrant parentage were risk factors for delayed and no lifetime screening. Interestingly, we found that this gradient persisted (at least partially) after adjusting for the women's socioeconomic characteristics. Only the level of income seemed to play a mediating role, but only partially. We observed differences between BCS and CCS which suggest that organized CCS could be effective in reducing socioeconomic and/or ethnic inequities. Socioeconomic status partially explained the screening nonparticipation on the part of French women of immigrant origin and foreign immigrants. This was more so the case with CCS than with BCS, which suggests that organized prevention programs might reduce social inequalities.

Superfluid density and condensate fraction in the BCS-BEC crossover regime at finite temperatures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukushima, N.; Ohashi, Y.; Faculty of Science and Technology, Keio University, Hiyoshi, Yokohama 223

2007-03-15

The superfluid density is a fundamental quantity describing the response to a rotation as well as in two-fluid collisional hydrodynamics. We present extensive calculations of the superfluid density {rho}{sub s} in the BCS-BEC crossover regime of a uniform superfluid Fermi gas at finite temperatures. We include strong-coupling or fluctuation effects on these quantities within a Gaussian approximation. We also incorporate the same fluctuation effects into the BCS single-particle excitations described by the superfluid order parameter {delta} and Fermi chemical potential {mu}, using the Nozieres-Schmitt-Rink approximation. This treatment is shown to be necessary for consistent treatment of {rho}{sub s} over themore » entire BCS-BEC crossover. We also calculate the condensate fraction N{sub c} as a function of the temperature, a quantity which is quite different from the superfluid density {rho}{sub s}. We show that the mean-field expression for the condensate fraction N{sub c} is a good approximation even in the strong-coupling BEC regime. Our numerical results show how {rho}{sub s} and N{sub c} depend on temperature, from the weak-coupling BCS region to the BEC region of tightly bound Cooper pair molecules. In a companion paper [Phys. Rev. A 74, 063626 (2006)], we derive an equivalent expression for {rho}{sub s} from the thermodynamic potential, which exhibits the role of the pairing fluctuations in a more explicit manner.« less

Associations of prepartum body condition score with occurrence of clinical endometritis and resumption of postpartum ovarian activity in dairy cattle.

PubMed

Kadivar, Ali; Ahmadi, Mohammad Rahim; Vatankhah, Mahmood

2014-01-01

This study was performed to investigate the effect of periparturient body condition score on the occurrence of clinical endometritis and postpartum resumption of ovarian activity in dairy cows. Eighty-seven lactating Holstein cows, fed with a total mixed ration diet, were included into the study. Body condition scoring (using a 5-point scale with quarter-point divisions) was performed by the same investigator using the visual technique every 2 weeks, from 2 weeks before until 6 weeks after calving. Palpation of the reproductive tract and ultrasonographic assessment of ovaries for detection of corpus luteum using a rectal linear probe was also performed at 2, 4, and 6 weeks after calving. Cows with clinical endometritis had significantly lower body condition score (BCS) than normal cows at all weeks pre- and postcalving, and cows that did not ovulate until 45 days after calving had a significantly lower BCS pre- and postpartum. Cows that did not ovulate until 45 days after calving also lost more BCS from 2 weeks before to 4 weeks after calving. Besides, first ovulation after calving take occurred later in cows with clinical endometritis compared to normal cows (P < 0.05). In conclusion, low BCS is a risk factor for postpartum endometritis and delayed cyclicity in dairy cows. BCS loss from dry-off to early lactation and occurrence of clinical endometritis can significantly affect postpartum ovarian activity.

Assessment of effects of a Cordia salicifolia extract on the radiolabeling of blood constituents and on the morphology of red blood cells.

PubMed

Frydman, Jacques Natan Grinapel; Rocha, Vanessa Camara; Benarroz, Monica Oliveira; Rocha, Gabrielle Souza; Pereira, Márcia Oliveira; de Souza da Fonseca, Adenilson; Bernardo-Filho, Mario

2008-12-01

Effects of a Cordia salicifolia (porangaba) extract on the labeling of blood cells (BCs) with technetium-99m ((99m)Tc) and on the morphology of red BCs were evaluated. Labeling of cellular and molecular structures with (99m)Tc depends on a reducing agent. Some physical characteristics, as visible absorbance spectrum, electric conductivity, and refractive index of this porangaba extract, were also determined. Blood samples from Wistar rats were incubated with porangaba extract or with 0.9% NaCl (control). Labeling of blood constituents with (99m)Tc was performed. Plasma (P) and BCs, both soluble (SF-P and SF-BC) and insoluble (IF-P and IF-BC) fractions, were separated. The radioactivity in each fraction was counted, and the percentage of radioactivity incorporated (%ATI) was calculated. Blood smears were prepared, fixed, and stained, and the morphology of the red BCs was evaluated. Data showed an absorbance peak at 480 nm and electric conductibility and refractive index concentration-dependent. Porangaba extract decreased significantly (P < .05) the BC, IF-P, and IF-BC %ATI, and no modifications were verified on the shape of red BCs. Analysis of the results reveals that some physical parameters could be useful to aid in characterizing the extract studied. Moreover, it is possible that chemical compounds of this extract could have chelating/redox actions or be capable of binding to plasma and/or cellular proteins.

Financial aspects of sentinel lymph node biopsy in early breast cancer.

PubMed

Severi, S; Gazzoni, E; Pellegrini, A; Sansovini, M; Raulli, G; Corbelli, C; Altini, M; Paganelli, G

2012-02-01

At present, early breast cancer is treated with conservative surgery of the primary lesion (BCS) along with axillary staging by sentinel lymph node biopsy (SLNB). Although the scintigraphic method is standardized, its surgical application is different for patient compliance, work organization, costs, and diagnosis related group (DRG) reimbursements. We compared four surgical protocols presently used in our region: (A) traditional BCS with axillary lymph node dissection (ALND); (B) BCS with SLNB and concomitant ALND for positive sentinel nodes (SN); (C) BCS and SLNB under local anaesthesia with subsequent ALND under general anaesthesia according to the SN result; (D) SLNB under local anaesthesia with subsequent BCS under local anaesthesia for negative SN, or ALND under general anaesthesia for positive SN. For each protocol, patient compliance, use of consumables, resources and time spent by various dedicated professionals, were analyzed. Furthermore, a detailed breakdown of 1-/2-day hospitalization costs was calculated using specific DRGs. We reported a mean costs variation that ranged from 1,634 to 2,221 Euros (protocols C and D). The number of procedures performed and the pathologists' results are the most significant variables affecting the rate of DRG reimbursements, that were the highest for protocol D and the lowest for protocol B. In our experience protocol C is the most suitable in terms of patient compliance, impact of surgical procedures, and work organization, and is granted by an appropriate DRG. We observed that a multidisciplinary approach enhances overall patient care and that a revaluation of DRG reimbursements is opportune.

Pathognomonic features of Angle's Class II division 2 malocclusion: A comparative cephalometric and arch width study

PubMed Central

Prasad, Singamsetty E.R.V.; Indukuri, Ravikishore Reddy; Singh, Rupesh; Nooney, Anitha; Palagiri, Firoz Babu; Narayana, Veera

2014-01-01

Background: A thorough knowledge of the salient features of malocclusion helps the clinician in arriving at a proper diagnosis and treatment plan, and also to predict the prognosis, prior to the onset of treatment process. Among the four classes of Angle's classification of malocclusion, Class II division 2 occurs with the least frequency. There is still continuing debate in the literature whether the Class II division 2 patients ascribe the pathognomonic skeletal and dental features. Aim of the study: The aim of this study is to describe the unique features of Angle's Class II division 2 malocclusion to differentiate it from Angle's Class II division 1 malocclusion. Materials and Methods: A total of 582 pre-treatment records (study models and cephalograms), with the age of patients ranging from 15 to 22 years, were obtained from the hospital records of Vishnu Dental College, Bhimavaram and Geetam's Dental College, Visakhapatnam. Out of these, 11 pre-treatment records were excluded because of lack of clarity. In the rest of the sample, 283 were Class II division 1 and 288 were Class II division 2. The lateral cephalograms were analyzed by using digiceph and the arch width analysis was done based on the anatomical points described by Staley et al. and Sergl et al. Results: An intergroup evaluation was done by using unpaired Student's “t” test. The skeletal vertical parameters, dental parameters, and the maxillary arch width parameters revealed a statistically significant difference between the two groups of malocclusion. Conclusion: Angle's Class II division 2 malocclusion has a pronounced horizontal growth pattern with decreased lower anterior facial height, retroclined upper anteriors, and significantly increased maxillary arch width parameters. PMID:25558449