bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical performance of the EMIT vancomycin assay.
Authors: Yeo K T , Traverse W , Horowitz G L
Published: January 2020

In evaluating the EMIT system for vancomycin used in the Cobas Bio centrifugal analyzer, we found two potential problems, each of which may have important clinical ramifications. First, precision, though acceptable in concentrations up to 30 mg/L, was marginal in the range above 30 mg/L. Second, when EMIT values were compared with those by fluorescent polarization immunoassay (TDx), we found a good correlation but a significant proportional bias: [EMIT] = (0.877)[TDx] + 0.435 mg/L (r = 0.971). The proportional bias was much more pronounced in specimens with high creatinine values than in specimens with normal values for creatinine. It remains to be determined which method is more nearly accurate. This imprecision and proportional bias in specimens with increased creatinines lead us to conclude that the EMIT vancomycin system should be used with caution.
Assay formats involving acridinium-ester-labeled DNA probes.
Authors: Arnold L J , Hammond P W , Wiese W A , Nelson N C
Published: January 2020

We describe the development of several hybridization assay formats involving acridinium-ester-labeled DNA probes. The simplest of these is a homogeneous assay procedure that requires only three steps to complete, including a 5-s detection step. Using this format, we have detected target sequences in the 10(-16) to 10(-17) mol range; when rRNA is the target, this translates to 3000 to 300 bacterial organisms. The entire assay can be carried out in less than 30 min. This is the first homogeneous DNA probe assay to be of practical use in the clinical laboratory, and it represents a major simplification of hybridization formats. We also demonstrate the use of this homogeneous assay format to discriminate single-base differences between two closely related target sequences and to detect DNA as well as RNA target molecules. By combining homogeneous hybrid discrimination with solid-phase separation, we have been able to decrease background readings from unhybridized probe to only a few parts per million. This enhances assay sensitivity about 10-fold, to a range of 10(-17) to 10(-18) mol of target. We are in the process of further improving the performance of these assays.
Rapid radioimmunoassay of circulating chromogranin A: in vitro stability, exploration of the neuroendocrine character of neoplasia, and assessment of the effects of organ failure.
Authors: O'Connor D T , Pandlan M R , Carlton E , Cervenka J H , Hslao R J
Published: January 2020

Chromogranin A is a useful probe of neuroendocrine neoplasia in humans. Here we optimize a rapid, sensitive radioimmunoassay modification for detecting chromogranin A in humans and other species. The site of chromogranin A circulation is the acellular plasma; platelets contain no chromogranin A immunoreactivity. The immunoreactivity in plasma is stable to repeated freezing and thawing, prolonged incubation at 37 degrees C, and lyophilization. Venipuncture alone resulted in modest (+ 12%, P less than 0.03) increase in chromogranin A in plasma. Several classic neuroendocrine neoplasia-pheochromocytoma, carcinoid tumor, neuroblastoma, and (vasoactive intestinal polypeptide)oma-produce markedly increased chromogranin A in plasma. By contrast, subjects with malignant melanoma, renal cell carcinoma, and thymoma all had normal values for chromogranin A. Hypersecretion of human choriogonadotropin beta subunit from both malignant (choriocarcinoma) and normal (placenta) syncytiotrophoblast cells was unaccompanied by an increase in chromogranin A, a dissociation compatible with the lack of granular storage and release of syncytiotrophoblastic peptide hormones. Both hepatic and renal failure resulted in increased chromogranin A in plasma, with renal failure leading to concentrations otherwise seen only in neuroendocrine neoplasia. These observations refine the diagnostic specificity of chromogranin A in plasma.
Aberrant lectin-binding activity of immunoglobulin G in serum from rheumatoid arthritis patients.
Authors: Parkkinen J
Published: January 2020

Structural studies of oligosaccharide chains of immunoglobulin G (IgG) in serum have revealed a specific galactosylation deficiency associated with rheumatoid arthritis (RA). Using a two-site lectin-immunofluorometric assay, I studied the interaction of IgG with immobilized lectins. Compared with control IgG, IgG purified from RA patients' sera bound up to 40-fold more strongly to immobilized Bandeiraea simplicifolia agglutinin II, a lectin that specifically binds agalacto forms of other glycoproteins. However, inhibition studies and treatment of IgG with glycosidase suggested that only a minor part of this binding was mediated by agalacto oligosaccharides of IgG. Furthermore, these IgG samples bound even more intensively to some other immobilized lectins, including Ricinus communis agglutinin (RCA). The binding to RCA was not inhibited by lactose, a hapten sugar of RCA, whereas other lectin species in solution effectively inhibited it. Compared with intact RA IgG, isolated F(ab')2 fragments displayed only low RCA-binding activity. These results indicate the existence of a carbohydrate-nondependent interaction between RA IgG and different plant lectins. With use of immobilized RCA, the lectin-immunofluorometric assay was rapid and reproducible for measuring the aberrant lectin-binding activity of IgG directly in diluted serum samples.
Biliary alkaline phosphatase measured by mini-column chromatography on DEAE-cellulose: application to detection of hepatobiliary diseases.
Authors: Yeh C T , Wei J S , Liaw Y F
Published: January 2020

Using chromatography on diethylaminoethyl (DEAE) cellulose, we measured biliary alkaline phosphatase (BALP; EC 3.1.3.1) activities in sera from 182 patients, most with hepatobiliary disorders but some with non-hepatobiliary diseases. Relative BALP activities were extremely low in otherwise healthy carriers of hepatitis B virus (mean: 5.4 U/L) and in patients with non-hepatobiliary diseases (mean: 5.3 U/L). Although BALP activities were detectable in some cases of liver cirrhosis and chronic hepatitis, these values were generally low (respective means: 12.6 and 12.0 U/L). High BALP activities were detected in patients with primary hepatocellular carcinoma, secondary metastatic liver tumors, and obstructive jaundice: mean values were 27.2, 37.2, and 73.6 U/L, respectively. There was no correlation between BALP activity and bilirubin concentration in patients with obstructive jaundice, nor between BALP activities in obstructive jaundice caused by stones and in those caused by extrahepatic tumor. Some patients with primary hepatocellular carcinoma had high BALP but low alpha-fetoprotein (AFP) values, some others the reverse. Based on AFP alone, the sensitivity for detecting hepatocellular carcinoma was 79%; adding BALP in parallel improved the sensitivity to 97%. We found minicolumn chromatography on DEAE-cellulose useful for determining BALP activity in hepatobiliary diseases.
Sources of imprecision in laboratories screening for congenital hypothyroidism: analysis of nine years of performance data.
Authors: Jewell S E , Slazyk W J , Smith S J , Hannon W H
Published: January 2020

We evaluated sources of imprecision in screening assays for congenital hypothyroidism performed between 1979 and 1987 by more than 45 laboratories participating in the national Neonatal Screening Standardization Program offered by the Centers for Disease Control. Reported concentrations were available from approximately 70,000 enriched dried-blood spot samples for thyroxin and thyrotropin, the primary and secondary screening assays, respectively. The most important sources of variation in assayed concentrations are within-laboratory imprecision and the methods or kits used. The importance of each of these sources depends on the analyte and its concentration. In most cases, the greatest source of measurement variation is attributable to within-laboratory imprecision (coefficient of variation 13% to 26%); however, kits are the largest source of variation at the lower concentrations of thyroxin. For both analytes, the greatest relative imprecision occurred at the low concentration, which was within the critical range of the cutoff values for detection of presumptive positive specimens. Imprecision in this range increases the risk of misclassifications. Minimizing within-laboratory imprecision and differences among kits seems to be the best way to improve overall efficiency of screening laboratories.
A micro-method for measuring total protein in cerebrospinal fluid by using benzethonium chloride in microtiter plate wells.
Authors: Luxton R W , Patel P , Keir G , Thompson E J
Published: January 2020

By using a benzethonium chloride concentration 12-fold that described originally (Clin Chem 1979;25:1317-9), we developed a reliable method suitable for routine measurement of total protein in cerebrospinal fluid. Only 10 microL of sample is required. Reactivity to immunoglobulin G (IgG) and to albumin (Alb) is similar, as is necessary for specimens that can have very varied IgG/Alb ratios. The assay, performed in a microtiter plate for ease of use, has a between-batch coefficient of variation of 3.4% for a protein concentration of 450 mg/L. This contrasts with a dye-binding technique with Ponceau S, for which the CV was 9% at the same concentration.
Monoclonal antibodies evaluated for use in a screening assay for conjugates of human serum albumin and pyridoxal 5'-phosphate.
Authors: Miller B B , Turner W E
Published: January 2020

This enzyme immunoassay (EIA) was developed to measure pyridoxal 5'-phosphate bound to albumin (PLP-HSA) in human serum. The monoclonal antibody titer was 1:2000 and a sequential saturation analysis curve, prepared with samples containing from 10 to 1000 nmol/L, showed a 50% inhibition of antibody at 50 nmol of the conjugate per liter. The lower limit of detection for PLP-HSA was 10 nmol/L, a sensitivity 1000-fold greater than that for any potential interferent. When serum samples gave negative results in the assay, we compared the antigenicity of the principal sites for PLP binding on HSA. It was apparent that the preferred physiological site was not antigenic; however, three additional sites for PLP binding on HSA elicited comparable antibody avidity. This EIA is potentially quite sensitive and specific for PLP-HSA, but considerable additional effort is required to convert serum PLP to an HSA-bound form detectable in the assay, which limits its application as a screening method.
Oligoclonal banding detected by urinary protein electrophoresis and immunofixation in two patients with the acquired immune deficiency syndrome and proteinuria.
Authors: Filomena C A
Published: January 2020

Monoclonal and oligoclonal banding has been observed in electrophoretograms of serum, cerebrospinal fluid, and urinary protein from patients infected with the human immunodeficiency virus (HIV). This is the first report of kappa oligoclonal banding in the protein electrophoretograms for urine but not for serum of two patients with the acquired immune deficiency syndrome (AIDS). Both patients had proteinuria, but only one had the nephrotic syndrome and renal failure. Serum oligoclonal banding in HIV-infected patients occurs much more frequently than in age-matched controls and may be detected before AIDS or lymphadenopathy syndrome evolves. The use of oligoclonal banding as a marker for HIV infection is currently under investigation. Urine as well as serum samples should be included in this research.
Antigens produced by recombinant DNA technology.
Authors: Fox J L , Klass M
Published: January 2020

Some of the greatest beneficiaries of the revolutionary advances in biotechnology over the past 15 years have been producers of diagnostic reagents, especially for the cloning and expression of antigens, primarily of viral origin. Recombinant DNA technology provides methods for producing antigens for diagnostic assays that are more highly purified, more specific, and safer to produce than viral culture and that are significantly less expensive to manufacture. Antigens so produced can be used for production of antibodies or antisera for competition assays, as reagents for mapping epitopes, as affinity-chromatography ligands for purification of antibodies or protein, and as research reagents. Their initial use in some hepatitis B assays may be primarily a cost-reduction application, but in other applications (e.g., HIV diagnostic tests) they present the first opportunity to commercially produce an otherwise very expensive antigen. Recombinant-DNA-produced antigens are also being used to develop safer vaccines, but not, however, without some consideration of the structural nature of immunodominant epitopes and the adequacy of the immune response.
Use of polymerase chain reaction for diagnosis of inherited disorders.
Authors: Boehm C D
Published: January 2020

The polymerase chain reaction (PCR) is a rapid method for generating a 10(6)- to 10(7)-fold increase in the number of copies of a discrete DNA or RNA sequence. The technique is being used for rapid prenatal diagnosis and carrier testing of several inherited disorders. After PCR, mutations producing single-gene disorders can be detected by several different methods, including endonuclease digestion and gel electrophoresis (applicable when a mutation affects an endonuclease recognition site), gel electrophoresis (used for detection of deletions), and hybridization to an oligonucleotide probe specific for a mutation. Less often, gene sequencing of a PCR product is used to rapidly identify a mutation. In addition, the PCR technique can be applied to polymorphism analysis to provide diagnosis by linkage analysis. In other areas, PCR is being used to detect and characterize microbial pathogens and to characterize mutations associated with carcinogenesis. The PCR method is useful in situations in which the amount of DNA sample is limited, such as in forensics and prenatal testing, or in which the quality of the DNA sample is poor.
Enzymatic amplification of RNA purified from crude cell lysate by reversible target capture.
Authors: Thompson J D , Decker S , Haines D , Collins R S , Feild M , Gillespie D
Published: January 2020

For increased clinical applications of nucleic acid probes to gene diagnosis, current procedures must be modified to become more amenable to the rapid processing of many samples with as few manipulations as possible. Here we summarize progress in the development of a strategy for performing molecular hybridization directly in lysate of biological samples dissolved in solutions containing the chaotropic agent, guanidine thiocyanate. Hybrids are purified by a process referred to as "reversible target capture," in which specific nucleic acid sequences are rapidly purified from crude lysate. We illustrate the use of this strategy to assay HIV-1 RNA and to rapidly purify HIV-1 RNA before enzymatic amplification by the polymerase chain reaction method.
S-100ao protein in blood and urine during open-heart surgery.
Authors: Usui A , Kato K , Abe T , Murase M , Tanaka M , Takeuchi E
Published: January 2020

Concentrations of S100a0 protein and CK-MB were measured by enzyme immunoassay in serial samples of arterial and coronary-sinus blood and urine taken from 26 patients who were undergoing mitral valve surgery. The mean concentration of arterial S100a0 in plasma was 0.32 (SD 0.28) ng/mL at the beginning of anesthesia, increased sharply after reperfusion, peaking [14.4 (SD 6.63) ng/mL] after 45 min of reperfusion, then decreased rapidly. The concentration of creatine kinase (CK) isoenzyme MB in arterial blood plasma was greatest 3 h after reperfusion [107 (SD 54.5) ng/mL]. S100a0 concentrations in urine increased dramatically after reperfusion [16,300 (SD 12,000) ng/h vs 44 (SD 32) ng/h], while CK-MB increased slightly [135 (SD 75) ng/h vs 19 (SD 12) ng/h]. These results suggest that S100a0 in cardiac muscle is released into the bloodstream during open-heart surgery and is discharged into the urine more rapidly than is CK-MB. Determination of S100a0 in plasma or urine thus may be useful for estimating damage to heart muscle during open-heart surgery.
Performance and diagnostic application of a two-site immunoradiometric assay for parathyrin in serum.
Authors: Ratcliffe W A , Heath D A , Ryan M , Jones S R
Published: January 2020

The "N-tact" immunoradiometric assay (IRMA) from INCSTAR for parathyrin (PTH) in serum involves a 125I-labeled affinity-purified antiserum to PTH 1-34 and an affinity-purified antiserum to PTH 39-84, the latter bound to a polystyrene bead. The mean detection limit, determined in six consecutive assays, was 4 ng/L. The within-batch CV was less than 7% in the range 15 to 2135 ng/L. The between-batch CV was 11.7% and 5.3% at 30 and 371 ng/L, respectively. Serum PTH in 14 proven cases of primary hyperparathyroidism was 49-808 (median 111) ng/L, undetectable (less than 5 ng/L) in 10 cases of primary hypoparathyroidism and in 10 cases of hypercalcemia associated with malignancy, compared with 7-39 ng/L in 45 normal subjects. PTH was 9 to 19 ng/L in four patients with familial benign hypercalcemia. In 39 patients with renal failure, apparent concentrations were 14 to 857 (median 133) ng/L, but sera from these patients pre-diluted with zero standard did not parallel dilutions of the standard, PTH 1-84. PTH concentrations were not significantly decreased in blood or serum kept at 20 degrees C for up to 6 h. After successful removal of a parathyroid adenoma, the mean half-time for disappearance of PTH in vivo in five hyperparathyroid patients was 3.3 min.
Reversed-phase HPLC separation of plasma norepinephrine, epinephrine, and dopamine, with three-electrode coulometric detection.
Authors: Musso N R , Vergassola C , Pende A , Lotti G
Published: January 2020

We present a method involving minor modifications of previous techniques, in which we use an ion-pair reversed-phase HPLC separation with three-electrode coulometry. Isocratic baseline separations can be obtained in 5 min. The sample preparation procedure, involving extraction with alumina at low temperature, allows good reproducibility (within-run and between-run CVs less than 10%) and improved sensitivity (less than 5 pg of each catecholamine per extract). This method allows approximately 70 low-cost plasma catecholamine analyses to be done in a working day.
Three direct spectrophotometric methods for determination of total bilirubin in neonatal and adult serum, adapted to the Technicon RA-1000 analyzer.
Authors: Harrison S P , Barlow I M
Published: January 2020

We adapted three bichromatic spectrophotometric methods for determining total bilirubin in serum, for use with the Technicon RA-1000 analyzer. The borate buffer (BOR) of Hertz et al. (Scand J Clin Invest 1974;33:215-30), the caffeine buffer (CAF) of Vink et al. (Clin Chem 1988;34:67-70), and the combined borate-caffeine buffer (B-C) of Franzini and Cattozzo (Clin Chem 1987;33:597-9) were compared. All methods required only 10 microL of serum, were precise (between-batch CVs less than 4.2%, analyte range 64-310 mumol/L), linear to 1000 mumol/L, and insensitive to interference from hemoglobin to 5 g/L. Lipemia, carotene, and methemalbumin interfered positively with each method but insignificantly unless in supranormal concentrations. Only the BOR method was sensitive to protein matrix effect. Neonates' results obtained with all three methods compared well with a Jendrassik-Gróf-based technique. However, samples from adults with cholestasis were overestimated, particularly by the CAF method, but the BOR and B-C methods would be suitable for "stat" bilirubin analysis in these samples.
Standardization of the Immunochemical Determination of Apolipoproteins A-I and B: A Report on the International Federation of Clinical Chemistry Meeting on Standardization of Apolipoprotein A-I and B Measurements (Basis for Future Consensus), Vienna, Austria, April 18-19, 1989
Authors: Marcovina Santica M , Albers John J
Published: January 2020

The central aim of standardization is to have accurate, reproducible apo A-I and B measurements for use in defining a person's risk for cardiovascular disease or in evaluating a therapeutic response. A common accuracy-based standardization program is indispensable in establishing international reference intervals for clinical use. It is therefore important that the standardization be implemented as soon as possible. Many problems of the standardization of apo A-I and B measurements have been presented and discussed in this meeting. Although immediate solutions to all the problems were not evident, following the recommendations from this meeting can significantly improve the standardization process.

The next step is to determine uniform reference intervals, followed by a consensus conference on apolipoproteins to define the cutpoints (cutoff values) for clinical decisions.
Protein Biomarker Quantification by Immunoaffinity Liquid Chromatography–Tandem Mass Spectrometry: Current State and Future Vision
Authors: Neubert Hendrik , Shuford Christopher M , Olah Timothy V , Garofolo Fabio , Schultz Gary A , Jones Barry R , Amaravadi Lakshmi , Laterza Omar F , Xu Keyang , Ackermann Bradley L
Published: January 2020

Immunoaffinity–mass spectrometry (IA-MS) is an emerging analytical genre with several advantages for profiling and determination of protein biomarkers. Because IA-MS combines affinity capture, analogous to ligand binding assays (LBAs), with mass spectrometry (MS) detection, this platform is often described using the term hybrid methods. The purpose of this report is to provide an overview of the principles of IA-MS and to demonstrate, through application, the unique power and potential of this technology. By combining target immunoaffinity enrichment with the use of stable isotope-labeled internal standards and MS detection, IA-MS achieves high sensitivity while providing unparalleled specificity for the quantification of protein biomarkers in fluids and tissues. In recent years, significant uptake of IA-MS has occurred in the pharmaceutical industry, particularly in the early stages of clinical development, enabling biomarker measurement previously considered unattainable. By comparison, IA-MS adoption by CLIA laboratories has occurred more slowly. Current barriers to IA-MS use and opportunities for expanded adoption are discussed. The path forward involves identifying applications for which IA-MS is the best option compared with LBA or MS technologies alone. IA-MS will continue to benefit from advances in reagent generation, more sensitive and higher throughput MS technologies, and continued growth in use by the broader analytical community. Collectively, the pursuit of these opportunities will secure expanded long-term use of IA-MS for clinical applications.
Text mining meets community curation: a newly designed curation platform to improve author experience and participation at WormBase
Authors: Arnaboldi Valerio , Raciti Daniela , Van Auken Kimberly , Chan Juancarlos N , Müller Hans-Michael , Sternberg Paul W
Published: January 2020

Biological knowledgebases rely on expert biocuration of the research literature to maintain up-to-date collections of data organized in machine-readable form. To enter information into knowledgebases, curators need to follow three steps: (i) identify papers containing relevant data, a process called triaging; (ii) recognize named entities; and (iii) extract and curate data in accordance with the underlying data models. WormBase (WB), the authoritative repository for research data on Caenorhabditis elegans and other nematodes, uses text mining (TM) to semi-automate its curation pipeline. In addition, WB engages its community, via an Author First Pass (AFP) system, to help recognize entities and classify data types in their recently published papers. In this paper, we present a new WB AFP system that combines TM and AFP into a single application to enhance community curation. The system employs string-searching algorithms and statistical methods (e.g. support vector machines (SVMs)) to extract biological entities and classify data types, and it presents the results to authors in a web form where they validate the extracted information, rather than enter it de novo as the previous form required. With this new system, we lessen the burden for authors, while at the same time receive valuable feedback on the performance of our TM tools. The new user interface also links out to specific structured data submission forms, e.g. for phenotype or expression pattern data, giving the authors the opportunity to contribute a more detailed curation that can be incorporated into WB with minimal curator review. Our approach is generalizable and could be applied to additional knowledgebases that would like to engage their user community in assisting with the curation. In the five months succeeding the launch of the new system, the response rate has been comparable with that of the previous AFP version, but the quality and quantity of the data received has greatly improved.
Raloxifene administration enhances retention in an orthodontic relapse model
Authors: Azami Niloufar , Chen Po-Jung , Mehta Shivam , Kalajzic Zana , Dutra Eliane H , Nanda Ravindra , Yadav Sumit
Published: January 2020

Background and objectives

Orthodontic relapse is a physiologic process that involves remodelling of the alveolar bone and principle periodontal ligament fibres. Raloxifene is an Food and Drug Administration (FDA)-approved selective oestrogen receptor modulator that inhibits systemic bone loss. In our study, we examined the effects of Raloxifene on alveolar bone modelling and orthodontic relapse in a rodent model.

Materials and methods

The efficacy of raloxifene was evaluated in 15-week-old male Wistar rats, 8 in each group (Control, Raloxifene, Raloxifene + 7-day relapse, Raloxifene + 14-day relapse) for a total of 42 days. All animals had 14 days of orthodontic tooth movement with a closed nickel–titanium coil spring tied from incisors to right first molar applying 5–8 gm of force. On the day of appliance removal, impression was taken with silicon material and the distance between first molar and second molar was filled with light-cured adhesive resin cement for retention phase. Raloxifene Retention, Raloxifene Retention + 7D, Raloxifene Retention + 14D groups received 14 daily doses of raloxifene (2.0 mg/kg/day) subcutaneously after orthodontic tooth movement during retention. After 14 days of retention, the retainer was removed and right first molar was allowed to relapse for a period of 14 days. Raloxifene injection continued for the Raloxifene + 14-day relapse group during relapse phase too. Control group received saline injections during retention. Animals were euthanized by CO2 inhalation. The outcome measure included percentage of relapse, bone volume fraction, tissue density, and histology analysis using tartrate-resistant acid phosphatase staining and determining receptor activator of nuclear factor-кB-ligand (RANKL) and osteoprotegerin expression.

Results

Raloxifene Retention + 14D group had significantly less (P < 0.05) orthodontic relapse when compared with other groups. There was a significant increase (P < 0.05) in bone volume fraction and tissue density in the Raloxifene Retention + 14D group when compared with other groups. Similarly, there was significant decrease in number of osteoclasts and RANKL expression in Raloxifene Retention + 14D group when compared with Raloxifene Retention + 7D group (P < 0.05).

Conclusion

Raloxifene could decrease post-orthodontic treatment relapse by decreasing bone resorption and indirectly enhancing bone formation.
The TATE model: a curriculum design framework for language teaching
Authors: Anderson Jason
Published: January 2020

This article proposes a curriculum design framework for instructed additional language learning comprising four phases: Text, Analysis, Task, Exploration (TATE). The framework is argued to be compatible with both natural order theory and skill acquisition theory through its ability to integrate meaning-focused tasks within a task-supported approach to language teaching that allows for both implicit and explicit learning processes to occur. It is presented as an integrated skills model consistent with contemporary research on the learning of both lexis and grammar, recognizing the importance of both written and spoken language practice during tasks. Evidence of current trends in global coursebook design is presented to support the framework from a sociocultural perspective. I argue that the framework is potentially compatible with CLIL and project-based approaches to language learning, but caution that the model is not presented as universally applicable; as such it is offered as a tool in the curriculum designer’s and teacher’s ‘toolbox’ for planning courses and curricula.
Falls Risk in Relation to Activity Exposure in High-Risk Older Adults
Authors: Del Din Silvia , Galna Brook , Lord Sue , Nieuwboer Alice , Bekkers Esther M J , Pelosin Elisa , Avanzino Laura , Bloem Bastiaan R , Olde Rikkert Marcel G M , Nieuwhof Freek , Cereatti Andrea , Della Croce Ugo , Mirelman Anat , Hausdorff Jeffrey M , Rochester Lynn
Published: January 2020

Background

Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME).

Methods

One hundred and nine older fallers, 38 fallers with mild cognitive impairment (MCI), and 128 fallers with Parkinson’s disease (PD) were randomly assigned to one of two active interventions: treadmill training only or treadmill training combined with a virtual reality component. Participants were tested before and after the interventions. Free-living walking activity was characterized by volume, pattern, and variability of ambulatory bouts using an accelerometer positioned on the lower back for 1 week. To evaluate that relationship between fall risk and activity, a normalized index was determined expressing fall rates relative to activity exposure (FRA index), with higher scores indicating a higher risk of falls per steps taken.

Results

At baseline, the FRA index was higher for fallers with PD compared to those with MCI and older fallers. Walking activity did not change after the intervention for the groups but the FRA index decreased significantly for all groups (p ≤ .035).

Conclusions

This work showed that V-TIME interventions reduced falls risk without concurrent change in walking activity. We recommend using the FRA index in future fall prevention studies to better understand the nature of intervention programs.
Longitudinal Association Between Energy Regulation and Fatigability in Mid-to-Late Life
Authors: Schrack Jennifer A , Wanigatunga Amal A , Zipunnikov Vadim , Kuo Pei-Lun , Simonsick Eleanor M , Ferrucci Luigi
Published: January 2020

Background

Deficits in energy production and utilization have been linked to higher fatigue and functional decline with aging. Lesser known is whether individuals with a combination of low peak energy capacity and high energy costs for mobility (eg, impaired energy regulation) are more likely to experience the onset and progression of high fatigability with aging.

Methods

Participants in the Baltimore Longitudinal Study of Aging (n = 651, 49.0% male, mean age 71.9, range 50–94) with ≥2 visits who completed fatigability (Borg rating of perceived exertion [RPE] after a 5-minute 1.5 mph treadmill walk), slow walking energy expenditure (VO2 mL/kg/min), and peak walking energy expenditure (VO2 mL/kg/min), testing between 2007 and 2018. The longitudinal association between each measure of energy expenditure, a ratio of energy cost-to-capacity, and perceived fatigability was modeled using mixed effects models adjusted for age, body composition, and comorbidities. Time to higher perceived fatigability (RPE ≥ 10) was modeled using Cox proportional hazards models.

Results

In continuous analyses, higher slow walking energy expenditure (p < .05) and a higher cost ratio (p ≤ .001) were associated with greater perceived fatigability over time. Cox proportional hazards models using tertiles of the cost ratio suggest that, compared to those in the lowest tertile, those in the middle and highest tertiles had 1.89 (95% confidence interval [CI]: 1.57–5.16) and 2.85 (95% CI: 1.05–3.40) times greater risk of developing higher fatigability, respectively.

Conclusion

Findings suggest that strategies to prevent fatigability should consider methods to improve energy regulation by targeting both the independent and combined effects of declining peak capacity and rising energy costs for mobility with aging.
Distinguishing the Impact of Age on Semantic and Nonsemantic Associations in Episodic Memory
Authors: Jarjat Gabriel , Ward Geoff , Hot Pascal , Portrat Sophie , Loaiza Vanessa M
Published: January 2020

Objectives

Refreshing, or the act of briefly foregrounding recently presented but now perceptually absent representations, has been identified as a possible source of age differences in working memory and episodic memory. We investigated whether the refreshing deficit contributes to the well-known age-related deficit for retrieving nonsemantic associations, but has no impact on existing semantic associations.

Method

Younger and older adults judged the relatedness of stimulus word pairs (e.g., pink–blue or pink–cop) after repeating or refreshing one of the words. During a later source recognition memory test, participants determined whether each item recognized as old was presented on the left or right (nonsemantic source memory) and presented in a related or unrelated pair (semantic source memory). The data were analyzed using a hierarchical Bayesian implementation of a multinomial model of multidimensional source memory.

Results

Neither age group exhibited a refreshing benefit to nonsemantic or semantic source memory parameters. There was a large age difference in nonsemantic source memory, but no age difference in semantic source memory.

Discussion

The study suggests that the nature of the association is most important to episodic memory performance in older age, irrespective of refreshing, such that source memory is unimpaired for semantically meaningful information.
A Review of Qualitative Research of Perception and Experiences of Dementia Among Adults From Black, African, and Caribbean Background: What and Whom Are We Researching?
Authors: Roche Moïse , Higgs Paul , Aworinde Jesutofunmi , Cooper Claudia
Published: January 2020

Background and Objectives

Black, African, and Caribbean (BAC) families are disproportionately affected by dementia but engage less with services. Studies reporting their experiences of dementia have tended to aggregate people from diverse backgrounds, without considering the impact of this diversity, or researchers’ ethnicities. We investigated participants’ and researchers’ ethnic identities, exploring how this relates to findings.

Research Design and Methods

We searched electronic databases in September 2018, for qualitative studies exploring how participants of Black ethnicity understand and experience dementia and dementia care. We reported participants’ and researchers’ ethnicities, and meta-synthesized qualitative findings regarding how ethnicity influences experiences and understanding of dementia.

Results

Twenty-eight papers reported 25 studies; in United States (n = 17), United Kingdom (n = 7), and Netherlands (n = 1). 350/492 (71%) of participants were in U.S. studies and described as African American; participants in U.K. studies as Caribbean (n = 45), African/Caribbean (n = 44), African (n = 28), Black British (n = 7), or Indo-Caribbean (n = 1); and in Netherlands as Surinamese Creole (n = 17). 6/25 (24%) of studies reported involving recruiters/interviewers matching participants’ ethnicity; and 14/25 (56%) involved an author/advisor from a BAC background during analysis/procedures. We identified four themes: Dementia does not relate to me; Inappropriate and disrespectful services; Kinship and responsibility; Importance of religion.

Discussion and Implications

Studies were mostly from a U.S. African American perspective, by researchers who were not of BAC background. Themes of dementia diagnosis and services feeling less relevant to participants than the majority population resonated across studies. We caution against the racialization of these findings, which can apply to many differing minority groups.
Activity of Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis Predicts Poorer Clinical Outcomes
Authors: Peverelle Matthew , Paleri Sarang , Hughes Jed , De Cruz Peter , Gow Paul J
Published: January 2020

Background

The impact of inflammatory bowel disease (IBD) activity on long-term outcomes after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is unknown. We examined the impact of post-LT IBD activity on clinically significant outcomes.

Methods

One hundred twelve patients undergoing LT for PSC from 2 centers were studied for a median of 7 years. Patients were divided into 3 groups according to their IBD activity after LT: no IBD, mild IBD, and moderate to severe IBD. Patients were classified as having moderate to severe IBD if they met at least 1 of 3 criteria: (i) Mayo 2 or 3 colitis or Simple Endoscopic Score–Crohn’s Disease ≥7 on endoscopy; (ii) acute flare of IBD necessitating steroid rescue therapy; or (iii) post-LT colectomy for medically refractory IBD.

Results

Moderate to severe IBD at any time post-transplant was associated with a higher risk of Clostridium difficile infection (27% vs 8% mild IBD vs 8% no IBD; P = 0.02), colorectal cancer/high-grade dysplasia (21% vs 3% both groups; P = 0.004), post-LT colectomy (33% vs 3% vs 0%) and rPSC (64% vs 18% vs 20%; P < 0.001). Multivariate analysis revealed that moderate to severe IBD increased the risk of both rPSC (relative risk [RR], 8.80; 95% confidence interval [CI], 2.81–27.59; P < 0.001) and colorectal cancer/high-grade dysplasia (RR, 10.45; 95% CI, 3.55–22.74; P < 0.001).

Conclusions

Moderate to severe IBD at any time post-LT is associated with a higher risk of rPSC and colorectal neoplasia compared with mild IBD and no IBD. Patients with no IBD and mild IBD have similar post-LT outcomes. Future prospective studies are needed to determine if more intensive treatment of moderate to severe IBD improves long-term outcomes in patients undergoing LT for PSC.
Participatory constitution-building in Fiji: A comparison of the 1993–1997 and the 2012–2013 processes
Authors: Saati Abrak
Published: January 2020

Participatory constitution-building during times of transition from war to peace or from authoritarian to democratic rule is quickly becoming an established norm. This article analyzes and compares two Fijian participatory processes; the 1993–1997 process and the 2012–2013 process. The purpose of doing so is to understand the extent to which these processes were genuinely participatory in terms of extending the Fijians’ possibility of influencing the content of the constitution. The article concludes that these processes were merely symbolic in terms of public participation; that there is not much that public participation can achieve in and by itself; and that the sequencing of public participation and secluded political elite negotiations in the context of constitution-building during times of transition is a field of research that is in dire need of further systematic analysis, particularly as an increasing amount of post-conflict and post-authoritarian states endeavor participatory constitution-building.
Virtually Cocompactly Cubulated Artin–Tits Groups
Authors: Haettel Thomas
Published: January 2020

We give a conjectural classification of virtually cocompactly cubulated Artin–Tits groups (i.e., having a finite index subgroup acting geometrically on a CAT(0) cube complex), which we prove for all Artin–Tits groups of spherical type, FC type, or two-dimensional type. A particular case is that for $n \geqslant 4$, the $n$-strand braid group is not virtually cocompactly cubulated.
Kinetics of Hepatitis B Core–Related Antigen and Anti–Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus–Hepatitis B Coinfection
Authors: Dezanet Lorenza N C , Maylin Sarah , Gabassi Audrey , Rougier Hayette , Miailhes Patrick , Lascoux-Combe Caroline , Chas Julie , Girard Pierre-Marie , Delaugerre Constance , Lacombe Karine , Boyd Anders
Published: January 2020

Background

The aim of the current study was to describe the kinetics of quantified hepatitis B core–related antigen (qHBcrAg) and quantified anti–hepatitis B core antibody (qAnti-HBc) during tenofovir (TDF) treatment and assess their ability to predict hepatitis B e antigen (HBeAg) seroclearance in patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus.

Methods

Serum qHBcrAg, qAnti-HBc, and hepatitis B virus DNA were obtained at TDF initiation and every 6–12 months. The on-treatment kinetics of qHBcrAg (ΔqHBcrAg) and qAnti-HBc (ΔqAnti-HBc) were estimated using mixed-effect linear regression. Hazard ratios (HRs) assessing the association between markers and HBeAg seroclearance were calculated using proportional hazards regression, and the sensitivity (Se) and specificity (Sp) of marker levels in predicting HBeAg seroclearance were assessed using time-dependent receiving operating characteristic curves.

Results

During a median of 4.6 years, the cumulative incidences of hepatitis B surface antigen and HBeAg seroclearance were 3.2% (n = 5 of 158) and 27.4% (n = 26 of 95), respectively. ΔqHBcrAg was biphasic in HBeAg-positive patients (−0.051 and −0.011 log10 U/mL/mo during ≤18 and >18 months, respectively) and monophasic in HBeAg-negative patients. ΔqAnti-HBc was monophasic regardless of HBeAg status. In HBeAg-positive patients, baseline qHBcrAg and qAnti-HBc levels were associated with HBeAg seroclearance (adjusted HR, 0.48/log10 U/mL [95% confidence interval, .33–.70] and unadjusted HR, 1.49/log10 Paul Ehrlich Institute units/mL [1.08–2.07], respectively). Cutoffs with the highest accuracy in predicting HBeAg seroclearance at 36 months were qHBcrAg <6.5 log10 U/mL at month 24 (Se, 1; Sp, 0.58) and baseline qAnti-HBc ≥4.1 log10 Paul Ehrlich Institute units/mL (Se, 0.42; Sp, 0.81).

Conclusions

In coinfected patients undergoing TDF, qHBcrAg/qAnti-HBc could be of use in monitoring HBeAg seroclearance.
Evaluation of swine enteroids as in vitro models forLawsonia intracellularisinfection1,2
Authors: Resende Talita Pilar , Medida Ramya Lekha , Vannucci Fabio A , Saqui-Salces Milena , Gebhart Connie
Published: January 2020

The enteric pathogen Lawsonia intracellularis is one of the main causes of diarrhea and compromised weight gain in pigs worldwide. Traditional cell-line cultures have been used to study L. intracellularis pathogenesis. However, these systems fail to reproduce the epithelial changes observed in the intestines of L. intracellularis-infected pigs, specifically, the changes in intestinal cell constitution and gene expression. A more physiologically accurate and state-of-the-art model is provided by swine enteroids derived from stem cell-containing crypts from healthy pigs. The objective of this study was to verify the feasibility of two-dimensional swine enteroids as in vitro models for L. intracellularis infection. We established both three- and two-dimensional swine enteroid cultures derived from intestinal crypts. The two-dimensional swine enteroids were infected by L. intracellularis in four independent experiments. Enteroid-infected samples were collected 3 and 7 d postinfection for analysis using real-time quantitative PCR and L. intracellularis immunohistochemistry. In this study, we show that L. intracellularis is capable of infecting and replicating intracellularly in two-dimensional swine enteroids derived from ileum.
Ingestion of organic acids and cinnamaldehyde improves tissue homeostasis of piglets exposed to enterotoxic Escherichia coli (ETEC)
Authors: Jiménez Milton J , Berrios Roger , Stelzhammer Sabine , Hohmann Miriam , Verri Waldiceu , Bracarense Ana Paula F R L
Published: January 2020

Organic acids (OA) and phytogenic compounds have been used in pig feeding as alternatives to antibiotic growth promoters. However, few studies have evaluated the systemic effect of the combination of these additives. The aim of this study was to assess the impact of an organic acid-based feed additive (OAFA), containing a blend of OA and cinnamaldehyde, on the tissue integrity of bacterially challenged piglets. Thirty weaned piglets 21 d old were used in a 19-d trial. Pigs received a standard diet during the first 7 d and afterward were allotted to five treatments. Dietary treatments were: Control (basal diet), Escherichia coli (basal diet and challenge with E. coli), colistin (basal diet + 200 mg colistin/kg feed + challenge with E. coli), OAFA1 (basal diet + 1 kg OAFA/ton feed + challenge with E. coli), and OAFA2 (basal diet + 2 kg OAFA/ton feed + challenge with E. coli). Seven days after the beginning of the treatment, the animals were challenged with an enterotoxic strain of E. coli (K88) for pigs. Five days after the challenge, all animals were euthanized for tissue sampling for histological and oxidative stress (intestine and liver) analysis. The reduced glutathione (GSH), ferric-reducing ability potential (FRAP), and free-radical scavenging ability (ABTS) assays were used to evaluate the intestinal antioxidant defense. Lipid peroxidation and superoxide anion production were evaluated through the levels of thiobarbituric acid-reactive substances (TBARS) and nitroblue tetrazolium (NBT) reduction assay, respectively. Animals fed the OAFA (1 and 2) diets had a decrease (P < 0.05) on histological changes in the intestine, liver, mesenteric lymph nodes, and spleen. Greater villus height (VH) and a higher ratio of VH to crypt depth (CD) were observed in animals of the OAFA2 group compared with the control and E. coli groups. The colistin and OAFA groups decreased (P < 0.05) the number of inflammatory cells in intestinal lamina propria. OAFA2 group increased (P < 0.05) intestinal cell proliferation. Colistin and OAFA2 supplementation induced a decrease (P < 0.05) in the levels of TBARS in both the intestine and liver compared with the E. coli group. In addition, an increase (P < 0.05) in GSH and FRAP ileal levels was observed in the OAFA2 group compared with E. coli group. These results show that the supplementation with OAFA in the diet of weaned piglets, especially at a dose of 2 kg/ton (OAFA2) protected tissues against enterotoxigenic Escherichia coli (ETEC) damage.