bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of rapid immunoassays for urgent ("stat") determinations of creatine kinase isoenyme MB.
Authors: Wu A H , Gornet T G , Harker C C , Chen H L
Published: January 2020

We compared the analytical performance of three immunoassays used to rapidly determine creatine kinase (EC 2.7.3.2; CK) isoenzyme MB in serum: Dade's "Stratus," Corning's "Magic Lite," and Hybritech's "Icon QSR CK-MB." Performance criteria included precision, analytical sensitivity, sample stability, and analytical and clinical correlation of results for serum samples taken from healthy individuals, patients with suspected and confirmed acute myocardial infarction, and patients after coronary artery bypass surgery. We also examined 31 samples taken from patients in the emergency room suspected of myocardial infarction, to evaluate the potential of these assays for early diagnosis. Although these assays differ in the manner in which CK-MB is measured, and therefore have different procedural requirements, we conclude that they are equivalent in overall assay performance. None of these assays, however, is sufficiently sensitive for early diagnosis of myocardial infarction; therefore, results cannot be used by cardiologists in deciding whether acute thrombolytic therapy should be given. Other management decisions, such as the optimal utilization of intensive-care bed space, may justify using these assays on a "stat" basis.
Alterations in lactate dehydrogenase isoenzyme patterns after therapy with streptokinase or streptococcal infection.
Authors: Podlasek S J , Dufour D R , McPherson R A
Published: January 2020

Serum samples from patients receiving intravenous streptokinase were examined for evidence of interaction in vivo between streptokinase and lactate dehydrogenase (EC 1.1.1.27; LD). We found that this treatment produced a band of LD activity that remained at the electrophoretic origin of LD isoenzyme analysis. Treatment with tissue plasminogen activator produced no such band. The streptokinase-LD complex could be removed from serum by ultracentrifugation. It remained in the circulation for as long as 48 h after streptokinase infusion. A similar phenomenon was observed in a case of pneumococcal sepsis. Examination of supernates from both cultures of several species of Gram-positive cocci revealed interactions between human LD and Streptococcus groups A and C and also Streptococcus pneumoniae. Evidently streptokinase can form complexes with LD in vivo after either streptokinase therapy or infection, with consequent alteration of the LD isoenzyme pattern.
Nitromethane interferes in assay of creatinine by the Jaffé reaction.
Authors: De Leacy E A , Brown N N , Clague A E
Published: January 2020

A patient who ingested a methanol/nitromethane mixture (model airplane fuel) showed an apparent plasma creatinine concentration of 8.0 mmol/L by the Jaffé reaction when the actual creatinine concentration, as measured by a specific enzymatic method, was 0.09 mmol/L. This effect was due to nitromethane in the plasma. Interference by nitromethane with the determination of creatinine by reaction with alkaline picrate (the Jaffé reaction) has not previously been reported. When nitromethane was added to plasma, the apparent creatinine measured was linearly related to the amount of nitromethane added. Comparison of spectral changes occurring during creatinine/picrate and nitromethane/picrate reactions show substantial similarity, suggesting a similar structure for the products. Although the findings are of interest for both their toxicological and analytical implications, the main interest lies with their suggestion of a model system for future investigation of the Jaffé reaction.
Genetically engineered antibodies.
Authors: Moore G P
Published: January 2020

The technology needed to genetically engineer antibodies is evolving rapidly and the potential utility of these novel reagents is being explored with vigor. The process includes cloning of the antibody genes, their in vitro manipulation and mutagenesis, expression in a suitable host/vector system, and, for commercial production, scale-up, purification, and product evaluation. At each step, significant advances have been achieved recently. For example: at first, antibody genes were cloned from genomic libraries by using adjacent DNA probes; techniques for rapid sequencing by primer extension of total mRNA allowed more specific screening with synthesized oligomers; finally, antibody genes can now be created de novo by chemical synthesis. Moreover, such synthesis allows total control over the antibody sequence so that molecules of any configuration can be produced. New reagents created in this way include murine antibodies whose constant regions and variable-region frameworks have been replaced with human sequence to enhance immunocompatibility with patients, to switch immunoglobulin class, or both.
High-molecular-mass ("biliary") isoenzyme of alkaline phosphatase and the diagnosis of liver dysfunction in cystic fibrosis.
Authors: Schoenau E , Boeswald W , Wanner R , Herzog K H , Boewing B , Boehles H J , Stehr K
Published: January 2020

The high-Mr isoenzyme of alkaline phosphatase (AP, EC 3.1.3.1), a highly sensitive index to cholestasis, was measured by liquid chromatography in 45 patients with cystic fibrosis. Results of serum tests for liver dysfunction--including gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, total AP, bilirubin, and bile acids--were compared with those for high-Mr AP. Values for high-Mr AP were increased in 44.4% of our patient population, with activities ranging from 0.4 to 17.3 U/L. The upper limit in the control group was 2.5 U/L. We find increased high-Mr AP to be a more sensitive indicator of liver dysfunction in patients with cystic fibrosis than are other tests.
Quantifying manganese in lymphocytes to assess manganese nutritional status.
Authors: Matsuda A , Kimura M , Kataoka M , Ohkuma S , Sato M , Itokawa Y
Published: January 2020

To clarify whether manganese nutritional status is better reflected by the manganese concentration in lymphocytes or in whole blood, we injected manganese solutions intravenously into manganese-deficient rats and determined manganese concentrations in lymphocytes, whole blood, and various tissues. The manganese concentrations in lymphocytes and tissues, but not in whole blood, were significantly less in manganese-deficient rats than in normal rats. These low values could be prevented by intravenous injection of manganese in a dose-dependent manner. These results suggest that, for assessment of manganese nutritional status, measurement of manganese in lymphocytes is better than that in whole blood.
HPLC analysis of brain and plasma for octanoic and decanoic acids.
Authors: Dean H G , Bonser J C , Gent J P
Published: January 2020

Two methods are described for determination of octanoic and decanoic acids in plasma and brain homogenate by "high-performance" liquid chromatography with ultraviolet detection. Analysis of the underivatized acids had a detection limit of only 50 mg/L, but formation of the p-bromophenacyl ester increased the sensitivity by 100-fold, to a detection limit of 0.5 mg/L. The latter procedure gave interassay coefficients of variation of 4.1% and 4.8% for octanoic and decanoic acids, respectively. The corresponding intra-assay values were 3.95% and 4.7% (n = 6). The derivative method, applied to samples of plasma from children receiving a medium-chain triglyceride (MCT) diet, gave values in agreement with results by gas-liquid chromatography. Results have also been obtained for samples from mice, either treated with the medium-chain triglyceride diet or given infusions of sodium octanoate.
Sialidase from different sources compared for electrophoretically separating serum alkaline phosphatase fractions from liver and bone.
Authors: Jung K , Pergande M , Klotzek S
Published: January 2020

We compared sialidase (neuraminidase; EC 3.2.1.18) from Vibrio cholerae, Clostridium perfringens, and Arthrobacter ureafaciens, seeking to improve the electrophoretic separation of the liver and bone isoenzymes of alkaline phosphatase (EC 3.1.3.1) on cellulose acetate membranes. Resolution is decisively determined by the type and activity of sialidase used in the preincubation of serum sample. Sialidase from Arthrobacter ureafaciens is not suited for this method. For optimal separation of the two isoenzymes we recommend the use of sialidase from Vibrio cholerae, determination of its activity with a standard procedure such as described here (mucin or sialyl lactose as substrates), and a final concentration of sialidase activity of 2.0 or 2.9 U/L (measured with mucin or sialyl lactose) in the incubation mixture.
Urinary excretion of some proteins and enzymes during normal pregnancy.
Authors: Cheung C K , Lao T , Swaminathan R
Published: January 2020

Total protein (TP), albumin (Alb), transferrin (TRF), retinol-binding protein (RPB), N-acetyl-beta-glucosaminidase (NAG), alanine aminopeptidase (AAP), gamma-glutamyltransferase (GGT), and creatinine (Cr) were measured in random (untimed) urine samples from 29 nonpregnant women and from pregnant subjects (11 in the first trimester, 34 in the second, and 37 in the third). The excretion of TP, Alb, TRF, NAG, and AAP (relative to creatinine) and the RBP concentration were all higher (P less than or equal to 0.05) in the second and third trimesters compared with values for the nonpregnant controls. The GGT/Cr ratio was significantly higher only in the third trimester. The increase in low-molecular-mass proteins and tubular enzymes suggests that at least part of the increase in Alb, TRF, and TP results from decreased tubular reabsorption. We conclude that excretion of both high- and low-molecular-mass proteins is increased during pregnancy.
Fog–Cloud Assisted IoT-Based Hierarchical Approach For Controlling Dengue Infection
Authors: Sood Sandeep Kumar , Sood Vaishali , Mahajan Isha , Sahil  
Published: January 2020

The past five decades have witnessed the unprecedented contribution of arboviral diseases towards global morbidity and disability. It is primarily attributed due to unplanned urbanization, population explosion and globalization. Out of these, dengue is considered the most important arboviral disease because of its predominant growth in the past. The presented study explores the immense potential of Internet of things (IoT), fog and cloud computing for providing technology-based healthcare solutions for dengue virus (DENV) infection. In this paper, a hierarchical healthcare computing system for controlling DENV infection using fog–cloud-assisted IoT is proposed. This system provides a real-time remote diagnosis of DENV infection in individuals and monitors and predicts their health sensitivity during its infection period. The system uses fog computing to diagnose the DENV infection status of the individuals using $k$-means clustering and generates immediate diagnostic alerts to individuals, at the fog layer. Furthermore, the system uses cloud computing to monitor and predict the probabilistic health sensitivity of the DENV-infected individuals using Bayesian belief network and artificial neural network, respectively, at the cloud layer. The prediction of health sensitivity in the proposed system helps the infected individuals and healthcare agencies in determining the health vulnerability of DENV-infected individuals and preventing severe or permanent health losses in the future. The proposed system is experimentally evaluated using well-defined approaches, which conform to its validity and applicability. The results obtained from the experimental evaluations of the proposed system acknowledge the performance superiority and high efficiency of the system in delivering DENV-related healthcare services in real time.
Clinical outcome after laparoscopic Nissen fundoplication in patients with GERD and PPI refractory heartburn
Authors: Schwameis Katrin , Oh Daniel , Green Kyle M , Lin Brenda , Zehetner Jörg , Lipham John C , Hagen Jeffrey A , DeMeester Steven R
Published: January 2020

Typical reflux symptoms that respond well to proton pump inhibitor (PPI) therapy are key factors predictive of an excellent outcome with antireflux surgery for gastroesophageal reflux disease (GERD). Our aim was to evaluate whether poor preoperative heartburn (HB) relief with PPIs was associated with a worse outcome after Nissen fundoplication. Patients with a main symptom of HB and a positive pH-test who had a laparoscopic Nissen fundoplication between January 2008 and December 2014 were included. Prior to surgery, patients graded how effectively their HB symptoms were relieved by PPIs. Three groups were defined: good response (76–100% relief), partial response (26–75% relief) and poor response (0–25% relief). Outcomes and satisfaction were assessed at a minimum of 1 year after fundoplication. There were 129 patients who met inclusion criteria and 75 agreed to participate. The median follow-up was 48 months. Prior to Nissen fundoplication 13 patients had a good HB response to PPI-therapy, 36 had a partial response and 26 had a poor response. All patients were satisfied with their HB relief after fundoplication (mean satisfaction score: 9.5/10) and there was no difference in satisfaction score or heartburn relief between groups. Heartburn symptoms that respond poorly to PPI therapy are reliably relieved with a Nissen fundoplication in patients with objectively confirmed GERD. Patient satisfaction after Nissen fundoplication was excellent and was similar in patients with poor versus excellent HB relief with preoperative PPI therapy. Therefore, antireflux surgery is an option for patients with HB and confirmed GERD regardless of the degree of relief of HB symptoms provided by PPI medications.
Validation of European Society of Cardiology pre-test probabilities for obstructive coronary artery disease in suspected stable angina
Authors: Bing Rong , Singh Trisha , Dweck Marc R , Mills Nicholas L , Williams Michelle C , Adamson Philip D , Newby David E
Published: January 2020

Aims 

To assess contemporary pre-test probability estimates for obstructive coronary artery disease in patients with stable chest pain.

Methods and results 

In this substudy of a multicentre randomized controlled trial, we compared 2019 European Society of Cardiology (ESC)-endorsed pre-test probabilities with observed prevalence of obstructive coronary artery disease on computed tomography coronary angiography (CTCA). We assessed associations between pre-test probability, 5-year coronary heart disease death or non-fatal myocardial infarction and study intervention (standard care vs. CTCA). The study population consisted of 3755 patients (30–75 years, 46% women) with a median pre-test probability of 11% of whom 1622 (43%) had a pre-test probability of >15%. In those who underwent CTCA (n = 1613), the prevalence of obstructive disease was 22%. When divided into deciles of pre-test probability, the observed disease prevalence was similar but higher than the corresponding median pre-test probability [median difference 2.3 (1.3–5.6)%]. There were more clinical events in patients with a pre-test probability >15% compared to those at 5–15% and <5% (4.1%, 1.5%, and 1.4%, respectively, P < 0.001). Across the total cohort, fewer clinical events occurred in patients who underwent CTCA, with the greatest difference in those with a pre-test probability >15% (2.8% vs. 5.3%, log rank P = 0.01), although this interaction was not statistically significant on multivariable modelling.

Conclusion 

The updated 2019 ESC guideline pre-test probability recommendations tended to slightly underestimate disease prevalence in our cohort. Pre-test probability is a powerful predictor of future coronary events and helps select those who may derive the greatest absolute benefit from CTCA.
The Political Economy of Liberal Democracy
Authors: Mukand Sharun W , Rodrik Dani
Published: January 2020

This paper develops a taxonomy of political regimes that distinguishes between three sets of rights—property rights, political rights and civil rights. The truly distinctive nature of liberal democracy is the protection of civil rights (equal treatment by the state for all groups) in addition to the other two. The paper shows how democratic transitions that are the product of a settlement between the elite (who care mostly about property rights) and the majority (who care about political rights), generically fail to produce liberal democracy. Instead, the emergence of liberal democracy requires low levels of inequality and weak identity cleavages.
Age- and Sex-Specific Changes in Lower-Limb Muscle Power Throughout the Lifespan
Authors: Alcazar Julian , Aagaard Per , Haddock Bryan , Kamper Rikke S , Hansen Sofie K , Prescott Eva , Alegre Luis M , Frandsen Ulrik , Suetta Charlotte
Published: January 2020

Background

Our main goal was to evaluate the pattern and time course of changes in relative muscle power and its constituting components throughout the life span.

Methods

A total of 1,305 subjects (729 women and 576 men; aged 20–93 years) participating in the Copenhagen Sarcopenia Study took part. Body mass index (BMI), leg lean mass assessed by dual-energy X-ray absorptiometry (DXA), and leg extension muscle power (LEP) assessed by the Nottingham power rig were recorded. Relative muscle power (normalized to body mass) and specific muscle power (normalized to leg lean mass) were calculated. Segmented regression analyses were used to identify the onset and pattern of age-related changes in the recorded variables.

Results

Relative muscle power began to decline above the age of 40 in both women and men, with women showing an attenuation of the decline above 75 years. Relative muscle power decreased with age due to (i) the loss of absolute LEP after the fourth decade of life and (ii) the increase in BMI up to the age of 75 years in women and 65 years in men. The decline in absolute LEP was caused by a decline in specific LEP up to the age of 75 in women and 65 in men, above which the loss in relative leg lean mass also contributed.

Conclusions

Relative power decreased (i) above 40 years by the loss in absolute power (specific power only) and the increase in body mass, and (ii) above ~70 years by the loss in absolute power (both specific power and leg lean mass).
Relationship Between Changes in Sedative-Hypnotic Medications Burden and Cognitive Outcomes in Hospitalized Older Adults
Authors: Smichenko Juliana , Gil Efrat , Zisberg Anna
Published: January 2020

Background

Sedative-hypnotic medications (SHMs) are frequently used in hospitalized older patients, despite undesirable effects on cognitive status. Although previous studies found a significant number of patients experience changes in SHM use during hospitalization, it is unclear which pattern of change leads to hospital-associated cognitive decline (HACD). This study tested the association between patterns of SHM change and HACD.

Methods

This secondary analysis study included 550 patients age 70+ who were cognitively intact at admission (Short Portable Mental Status Questionnaire [SPMSQ] ≥8). HACD was defined as at least 1-point decline in SPMSQ between admission and discharge. Changes in sedative burden (SB) before and during hospitalization (average SB of all hospitalization days) were coded using the Drug Burden Index sorting study participants into four groups: without SB (n = 254), without SB changes (n = 132), increased SB (n = 82), and decreased SB (n = 82).

Results

Incidence of HACD was 233/550 (42.4%). In multivariate logistic analysis controlling for demographic characteristics, length of stay, severity of acute illness, comorbidity, SB score at home, pain on admission and depression, the odds of HACD were 2.45 (95% CI: 1.16 to 5.13) among participants with increased SB, 2.10 (95% CI: 1.13 to 3.91) among participants without SB changes, compared with participants with decreased SB.

Conclusion

Older patients whose SB is increased or does not change are at higher risk for acquired cognitive decline than are those whose SB is reduced. Identifying patients with a potential increase in SB and intervening to reduce it may help to fight HACD.
Cholinergic White Matter Lesions, AD-Signature Cortical Thickness, and Change in Cognition: The Northern Manhattan Study
Authors: Caunca Michelle R , Siedlecki Karen , Cheung Ying Kuen , Alperin Noam , Lee Sang H , Elkind Mitchell S V , Sacco Ralph L , Wright Clinton B , Rundek Tatjana
Published: January 2020

Background

How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer’s disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition.

Methods

Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition.

Results

Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = −0.17, SE = 0.05, p = .001) and over time (standardized β = −0.28, SE = 0.09, p = .003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = −0.02, SE = 0.01, p = .023; change: standardized β = −0.03, SE = 0.02, p = .040).

Conclusions

Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.
A draft genome sequence of the elusive giant squid, Architeuthis dux
Authors: da Fonseca Rute R , Couto Alvarina , Machado Andre M , Brejova Brona , Albertin Carolin B , Silva Filipe , Gardner Paul , Baril Tobias , Hayward Alex , Campos Alexandre , Ribeiro Ângela M , Barrio-Hernandez Inigo , Hoving Henk-Jan , Tafur-Jimenez Ricardo , Chu Chong , Frazão Barbara , Petersen Bent , Peñaloza Fernando , Musacchia Francesco , Alexander Graham C , Osório Hugo , Winkelmann Inger , Simakov Oleg , Rasmussen Simon , Rahman M Ziaur , Pisani Davide , Vinther Jakob , Jarvis Erich , Zhang Guojie , Strugnell Jan M , Castro L Filipe C , Fedrigo Olivier , Patricio Mateus , Li Qiye , Rocha Sara , Antunes Agostinho , Wu Yufeng , Ma Bin , Sanges Remo , Vinar Tomas , Blagoev Blagoy , Sicheritz-Ponten Thomas , Nielsen Rasmus , Gilbert M Thomas P
Published: January 2020

Background

The giant squid (Architeuthis dux; Steenstrup, 1857) is an enigmatic giant mollusc with a circumglobal distribution in the deep ocean, except in the high Arctic and Antarctic waters. The elusiveness of the species makes it difficult to study. Thus, having a genome assembled for this deep-sea–dwelling species will allow several pending evolutionary questions to be unlocked.

Findings

We present a draft genome assembly that includes 200 Gb of Illumina reads, 4 Gb of Moleculo synthetic long reads, and 108 Gb of Chicago libraries, with a final size matching the estimated genome size of 2.7 Gb, and a scaffold N50 of 4.8 Mb. We also present an alternative assembly including 27 Gb raw reads generated using the Pacific Biosciences platform. In addition, we sequenced the proteome of the same individual and RNA from 3 different tissue types from 3 other species of squid (Onychoteuthis banksii, Dosidicus gigas, and Sthenoteuthis oualaniensis) to assist genome annotation. We annotated 33,406 protein-coding genes supported by evidence, and the genome completeness estimated by BUSCO reached 92%. Repetitive regions cover 49.17% of the genome.

Conclusions

This annotated draft genome of A. dux provides a critical resource to investigate the unique traits of this species, including its gigantism and key adaptations to deep-sea environments.
A high-quality chromosomal genome assembly of Diospyros oleifera Cheng
Authors: Suo Yujing , Sun Peng , Cheng Huihui , Han Weijuan , Diao Songfeng , Li Huawei , Mai Yini , Zhao Xing , Li Fangdong , Fu Jianmin
Published: January 2020

Background

Diospyros oleifera Cheng, of the family Ebenaceae, is an economically important tree. Phylogenetic analyses indicate that D. oleifera is closely related to Diospyros kaki Thunb. and could be used as a model plant for studies of D. kaki. Therefore, development of genomic resources of D. oleifera will facilitate auxiliary assembly of the hexaploid persimmon genome and elucidate the molecular mechanisms of important traits.

Findings

The D. oleifera genome was assembled with 443.6 Gb of raw reads using the Pacific Bioscience Sequel and Illumina HiSeq X Ten platforms. The final draft genome was ~812.3 Mb and had a high level of continuity with N50 of 3.36 Mb. Fifteen scaffolds corresponding to the 15 chromosomes were assembled to a final size of 721.5 Mb using 332 scaffolds, accounting for 88.81% of the genome. Repeat sequences accounted for 54.8% of the genome. By de novo sequencing and analysis of homology with other plant species, 30,530 protein-coding genes with an average transcript size of 7,105.40 bp were annotated; of these, 28,580 protein-coding genes (93.61%) had conserved functional motifs or terms. In addition, 171 candidate genes involved in tannin synthesis and deastringency in persimmon were identified; of these chalcone synthase (CHS) genes were expanded in the D. oleifera genome compared with Diospyros lotus, Camellia sinensis, and Vitis vinifera. Moreover, 186 positively selected genes were identified, including chalcone isomerase (CHI) gene, a key enzyme in the flavonoid-anthocyanin pathway. Phylogenetic tree analysis indicated that the split of D. oleifera and D. lotus likely occurred 9.0 million years ago. In addition to the ancient γ event, a second whole-genome duplication event occurred in D. oleifera and D. lotus.

Conclusions

We generated a high-quality chromosome-level draft genome for D. oleifera, which will facilitate assembly of the hexaploid persimmon genome and further studies of major economic traits in the genus Diospyros.
The signaling pathways implicated in impairment of hepatic autophagy in glycogen storage disease type Ia
Authors: Gautam Sudeep , Zhang Lisa , Arnaoutova Irina , Lee Cheol , Mansfield Brian C , Chou Janice Y
Published: January 2020

Glucose-6-phosphatase-α (G6Pase-α or G6PC) deficiency in glycogen storage disease type-Ia (GSD-Ia) leads to impaired hepatic autophagy, a recycling process important for cellular metabolism and homeostasis. Autophagy can be regulated by several energy sensing pathways, including sirtuin 1 (SIRT1), forkhead box O (FoxO), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-α (PPAR-α), and mammalian target of rapamycin (mTOR). Using 10-day old global G6pc-deficient (G6pc−/−) mice, hepatic autophagy impairment was attributed to activation of mTOR and inhibition of AMPK signaling. In other studies, using adult liver-specific G6pc-deficient mice at both pre-tumor and tumor stages, hepatic autophagy impairment was attributed to downregulation of SIRT1 signaling and mTOR was not implicated. In this study, we provide a detailed analysis of the major autophagy pathways in young G6pc−/− mice over the first 4 weeks of life. We show that impaired SIRT1, FoxO3a, AMPK, and PPAR-α signaling are responsible for autophagy impairment but mTOR is involved minimally. Hepatic SIRT1 overexpression corrects defective autophagy, restores the expression of FoxO3a and liver kinase B1 but fails to normalize impaired PPAR-α expression or metabolic abnormalities associated with GSD-Ia. Importantly, restoration of hepatic G6Pase-α expression in G6pc−/− mice corrects defective autophagy, restores SIRT1/FoxO3a/AMPK/PPAR-α signaling and rectifies metabolic abnormalities. Taken together, these data show that hepatic autophagy impairment in GSD-Ia is mediated by downregulation of SIRT1/FoxO3a/AMPK/PPAR-α signaling.
From Interlaken to Copenhagen: What Has Become of the Proposals Aiming to Reform the Functioning of the European Court of Human Rights?
Authors: Glas Lize R
Published: January 2020

The States Parties to the European Convention on Human Rights have adopted five declarations on the future of the European Court of Human Rights since 2010. These declarations identified problems surrounding the Convention system and proposed reform measures. This article examines what has become of the proposals aiming to reform the Court’s functioning, which will lead to insight into the problems surrounding the system, the type of solutions proposed and whether the declarations have led to change. The article also discusses the background to the conferences and characterises the focus of each declaration. The conclusion is that most proposals have not been implemented, mainly due to principled or practical opposition of the Court, and that the implemented proposals have not led to profound change. The influence of the declarations should not be overstated therefore, although they can be of political significance by offering support to or criticising the Court.
Evaluation of EBV Status and Thiopurine Use in Pediatric Inflammatory Bowel Disease: Time to be a Standard of Care
Authors: Martinelli Massimo , Miele Erasmo
Published: January 2020

Epstein-Barr virus status is helpful in guiding physicians’ decision on thiopurine use in children with pediatric inflammatory bowel disease.
Increased Colonic Epithelial Permeability and Mucosal Eosinophilia in Ulcerative Colitis in Remission Compared With Irritable Bowel Syndrome and Health
Authors: Katinios Georgios , Casado-Bedmar Maite , Walter Susanna A , Vicario Maria , González-Castro Ana M , Bednarska Olga , Söderholm Johan D , Hjortswang Henrik , Keita Åsa V
Published: January 2020

Background

Barrier dysfunction is recognized as a pathogenic factor in ulcerative colitis (UC) and irritable bowel syndrome (IBS), but it is unclear to what extent the factors related to barrier dysfunction are disease-specific. The aim of this study was to compare these aspects in UC patients in remission, IBS patients, and healthy controls (HCs).

Methods

Colonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed, and 15 HCs. Ulcerative colitis patients had recently been treated for relapse, and biopsies were taken from earlier inflamed areas. Biopsies were mounted in Ussing chambers for measurements of intestinal paracellular permeability to 51chromium (Cr)-ethylenediaminetetraacetic acid (EDTA). In addition, biopsies were analyzed for mast cells and eosinophils by histological procedures, and plasma tumor necrosis factor (TNF)-α was assessed by ELISA.

Results

Ussing chamber experiments revealed an increased 51Cr-EDTA permeability in UC and IBS (P < 0.05). The 51Cr-EDTA permeability was higher in UC compared with IBS (P < 0.005). There were increased numbers of mucosal mast cells and eosinophils in UC and IBS and more eosinophils in UC compared with IBS (P < 0.05). Also, increased extracellular granule content was found in UC compared with HCs (P < 0.05). The 51Cr-EDTA permeability correlated significantly with eosinophils in all groups. Plasma TNF-α concentration was higher in UC compared with IBS and HCs (P < 0.0005).

Conclusions

Results indicate a more permeable intestinal epithelium in inactive UC and IBS compared with HCs. Ulcerative colitis patients, even during remission, demonstrate a leakier barrier compared with IBS. Both eosinophil numbers and activation state might be involved in the increased barrier function seen in UC patients in remission.
Murine Precision-cut Intestinal Slices as a Potential Screening Tool for Antifibrotic Drugs
Authors: Iswandana Raditya , Pham Bao Tung , Suriguga Su , Luangmonkong Theerut , van Wijk Louise A , Jansen Yvette J M , Oosterhuis Dorenda , Maria Mutsaers Henricus Antonius , Olinga Peter
Published: January 2020

Background

Intestinal fibrosis is a hallmark of Crohn’s disease. Here, we investigated the impact of several putative antifibrotic compounds on the expression of fibrosis markers using murine precision-cut intestinal slices.

Methods

Murine precision-cut intestinal slices were cultured for 48 hours in the presence of profibrotic and/or antifibrotic compounds. The fibrotic process was studied on gene and protein level using procollagen 1a1 (Col1α1), heat shock protein 47 (Hsp47), fibronectin (Fn2), and plasminogen activator inhibitor-1 (Pai-1). The effects of potential antifibrotic drugs mainly inhibiting the transforming growth factor β (TGF-β) pathway (eg, valproic acid, tetrandrine, pirfenidone, SB203580, and LY2109761) and compounds mainly acting on the platelet-derived growth factor (PDGF) pathway (eg, imatinib, sorafenib, and sunitinib) were assessed in the model at nontoxic concentrations.

Results

Murine precision-cut intestinal slices remained viable for 48 hours, and an increased expression of fibrosis markers was observed during culture, including Hsp47, Fn2, and Pai-1. Furthermore, TGF-β1 stimulated fibrogenesis, whereas PDGF did not have an effect. Regarding the tested antifibrotics, pirfenidone, LY2109761, and sunitinib had the most pronounced impact on the expression of fibrosis markers, both in the absence and presence of profibrotic factors, as illustrated by reduced levels of Col1α1, Hsp47, Fn2, and Pai-1 after treatment. Moreover, sunitinib significantly reduced Hsp47 and Fn2 protein expression and the excretion of procollagen 1.

Conclusions

Precision-cut intestinal slices can successfully be used as a potential preclinical screening tool for antifibrotic drugs. We demonstrated that sunitinib reduced the expression of several fibrosis markers, warranting further evaluation of this compound for the treatment of intestinal fibrosis.
Radiotherapy-related skin ulcer communicating with a left ventricular aneurysm
Authors: Takaki Jun , Hosoda Yasuhito , Okamoto Ken , Fukui Toshihiro
Published: January 2020

Although radiation therapy is widely used to treat breast cancer, high doses of radiation may cause various complications. We report a case of a left ventricular aneurysm complicated with an intractable skin ulcer caused by radiation therapy for breast cancer. The communication between the aneurysm and skin ulcer caused severe bleeding. An urgent left ventricular repair and chest wall reconstruction with a rectus abdominis flap were performed successfully.
Efficiency evaluation and optimization of rural ecotourism space based on DEA model
Authors: Liang Yezhang , Shi Chunsheng
Published: January 2020

Since the reform and opening up, with the development of China’s economy, the demand for tourism has been increased. The traditional agriculture has not been able to satisfy the diversified consumption demand; as a result, the rural ecotourism develops rapidly. Based on such a situation, the data envelopment analysis (DEA) model was used in this study; the relevant data of Guangxi province such as the number of star hotels and number of tourists were referred to. The efficiency of rural ecotourism space was calculated. According to evaluation analysis of spatial dynamic efficiency, it could be found that although the comprehensive technical efficiency of the southeast coastal areas was lower than 1, it was still higher than other regions. The pure technical efficiency of many regions was equal to 1, and the scale benefits were increasing. Regions with moderate political and economic levels had high pure technical efficiency and maintained above the national level, but they were relatively small in scale and needed to increase input indicators. However, the comprehensive technical efficiency of relatively backward areas in northwest China was relatively low, which remained at about 0.3. Therefore, more investment and government support are needed to expand the scale.
Self-Reinforcing Civilian Control: A Measurement-Based Analysis of Civil-Military Relations
Authors: Kenwick Michael R
Published: January 2020

How does the passage of time contribute to the establishment of civilian control of the State? We argue that civilian dominance of politics is achieved once civilianized institutions are adopted and sufficient time has passed to permit: (1) the development of a shared norm of civilian control within the military and (2) learning among military elites that fosters a belief that civilian rule is robust to military challenges. As a result, civilian control is self-reinforcing. We evaluate these claims by developing and validating a latent variable model of self-reinforcing institutional dynamics. We generate estimates of civilian control for all countries, 1945–2010, and find strong evidence that civilian control self-reinforces, but incrementally and over the course of several decades.
A multicomponent mycotoxin deactivator modifies the response of the jejunal mucosal and cecal bacterial community to deoxynivalenol contaminated feed and oral lipopolysaccharide challenge in chickens1
Authors: Metzler-Zebeli Barbara U , Lucke Annegret , Doupovec Barbara , Zebeli Qendrim , Böhm Josef
Published: January 2020

Mycotoxin deactivators are a widely used strategy to abrogate negative effects of mycotoxin-contaminated feed. It has not been adequately evaluated whether these deactivators may detoxify bacterial toxins in the intestinal lumen and subsequently lower the inflammatory response in chickens. The present objective was to study the effect of a multicomponent mycotoxin deactivator (B), containing a bentonite and a bacterial strain capable to enzymatically biotransform trichothecenes especially deoxynivalenol (DON), when supplemented to a DON-contaminated feed in combination with an oral lipopolysaccharide challenge on visceral organ size, expression of innate immune genes and mucosal permeability in the small intestine as well as on the cecal bacterial composition and metabolites in broiler chickens. Eighty 1-d-old male chickens were randomly allotted to four treatment groups in two replicate batches (n = 10/treatment/replicate): 1) basal diet without DON (CON), 2) CON diet supplemented with B (2.5 mg B/kg feed) (CON-B), 3) CON diet contaminated with 10 mg DON/kg feed (DON), and 4) DON diet supplemented with 2.5 mg B/kg feed (DON-B). In half of the chickens per treatment, effects were assessed under nonchallenge conditions, whereas in the other half of birds, to increase their intestinal bacterial toxin load, effects were tested after an oral challenge with 1 mg LPS/kg BW from Escherichia coli O55:B5 on the day before sampling. DON reduced (P < 0.05) the weight of bursa fabricii and thymus. DON increased the expression level of intestinal alkaline phosphatase at the duodenal mucosa (P = 0.027) but did not modify jejunal gene expression and mucosal permeability. The LPS challenge decreased the jejunal MUC2 expression but increased ZO1 and IL6 expression compared to the unchallenged animals (P < 0.05). DON × B interactions indicated lower expression of IL10 in duodenum and NFKB in jejunum with the B diet but higher expression with the DON-B diet (P = 0.050). Furthermore, the B lowered jejunal expression of NFKB and IL6 but only in LPS-challenged chickens (P < 0.05). Alterations in the cecal microbiota composition and VFA profile were likely associated with alterations in host physiology in the small intestine caused by DON, B, and LPS. According to the present data, B appeared to have potential to detoxify antigens other than DON in the intestinal lumen of chickens, whereby the toxin load may limit the efficacy of B to modify the intestinal and systemic response as indicated by interactions of DON, B, and LPS.
Survival Outcomes of Screening with Breast MRI in Women at Elevated Risk of Breast Cancer
Authors: Bae Min Sun , Sung Janice S , Bernard-Davila Blanca , Sutton Elizabeth J , Comstock Christopher E , Morris Elizabeth A
Published: January 2020

Objective

To determine survival outcomes in women with breast cancer detected at combined screening with breast MRI and mammography versus screening mammography alone.

Methods

This is an institutional review board-approved retrospective study, and the need for informed consent was waived. A total of 3002 women with an increased risk of breast cancer were screened between 2001 and 2004. Of the 3002 women, 1534 (51.1%) had 2780 combined screenings (MRI and mammography) and 1468 (48.9%) had 4811 mammography-only screenings. The Χ2 test and the Kaplan-Meier method were used to compare cancer detection rates and survival rates.

Results

The overall cancer detection rate was significantly higher in the MRI plus mammography group compared with the mammography-only group (1.4% [40 of 2780] vs 0.5% [23 of 4811]; P < 0.001). No interval cancers occurred in the MRI plus mammography group, whereas 9 interval cancers were found in the mammography-only group. During a median follow-up of 10.9 years (range: 0.7 to 15.2), a total of 11 recurrences and 5 deaths occurred. Of the 11 recurrences, 6 were in the MRI plus mammography group and 5 were in the mammography-only group. All five deaths occurred in the mammography-only group. Disease-free survival showed no statistically significant difference between the two groups (P = 0.32). However, overall survival was significantly improved in the MRI plus mammography group (P = 0.002).

Conclusion

Combined screening with MRI and mammography in women at elevated risk of breast cancer improves cancer detection and overall survival.
Comparative Insight into the Bacterial Communities in Alate and Apterous Morphs of Brown Citrus Aphid (Hemiptera: Aphididae)
Authors: Shang Feng , Niu Jinzhi , Ding Bi-Yue , Wang Jin-Jun
Published: January 2020

Wing polyphenism (alate and apterous morphs) in aphids is a trade-off between dispersal and reproduction. How bacterial communities are associated with wing polyphenism in aphids is still not clearly understood. This study used 16S rRNA sequencing to examine the differences in diversity of the bacterial community between alate and apterous morphs in Aphis citricidus, the main vector of the Citrus tristeza virus. Eighty-one operational taxonomic units (OTUs) belonging to 37 orders, 34 classes, and 13 phyla were identified from all samples. Among these OTUs, Wolbachia (79.17%), Buchnera (17.64%), and Pseudomonas (2.99%) were the dominant bacterial genera. The diversity of symbionts varied between the two morphs; apterous morphs had more bacterial diversity (69 OTUs belonging to 45 families, 21 classes, and 12 phyla) than alate morphs (45 OTUs belonging to 36 families, 15 classes, and 10 phyla). In addition, the abundance of five OTUs was significantly different between two morphs. Among these OTUs, two Pseudomonas species (Pseudomonas_brenneri [OTU21] and unclassified_Pseudomonas [OTU13]) represented a high proportion (3.93% and 2.06%) in alate morphs but were present in low abundance (0.006% and 0.002%) in apterous morphs. RT-qPCR showed consistent results with high-throughput DNA sequencing. The preliminary survey showed the difference in composition and frequency of bacteria between alate and apterous morphs. Thus, the results contribute to anew insight of microorganisms that may be involved in wing dimorphism and helpful for controlling the dispersal of this pest through artificial elimination or reinfection of bacterial symbionts or targeting symbiosis-related host genes by RNA interference in future.
Numerical simulations of acoustic isolators in monopole acoustic logging while drilling based on phononic crystal structures
Authors: Yang Peinian , Chen Dehua , He Xiao , Ji Yunjia , Wang Xiuming
Published: January 2020

In acoustic logging while drilling (ALWD), it is crucial to have an ALWD isolator to reduce collar waves and to meet the requirement of wideband acoustic measurements. In this work, we proposed a new acoustic isolator based on phononic crystal structures for reducing collar waves, and its acoustic insulation performance is numerically studied through the finite difference simulation. For the typical ALWD tool, the optimized acoustic isolator has eight-section graded grooves and each contains 11 small grooves varying from 3 to 5 mm, with an interval of 0.2 m between adjacent sections. Performances of the isolators we designed are verified by numerical results. The attenuation effects of the improved isolator and the traditional one on collar arrivals are compared. The comparison of synthetic waveforms reveals that the newly proposed design with grooves characterized by gradually varying width displays better acoustic isolation performance than the traditional isolator with uniform grooves when operated with various source central frequencies from 13 to 15 kHz. By applying the proposed isolator, the formation longitudinal wave velocities can be separated effectively from the wave group containing the collar waves in the fast formation model. These studies may be useful for the ALWD tool design and data processing.
Attraction Versus Capture: Efficiency of BG-Sentinel Trap Under Semi-Field Conditions and Characterizing Response Behaviors for Female Aedes aegypti (Diptera: Culicidae)
Authors: Amos Brogan A , Staunton Kyran M , Ritchie Scott A , Cardé Ring T
Published: January 2020

Aedes aegypti (L.) is an important vector of viruses causing dengue, Zika, chikungunya, and yellow fever and as such is a threat to public health worldwide. Effective trapping methods are essential for surveillance of both the mosquito species and disease presence. The BG-Sentinel (BGS) is a widely used to trap Ae. aegypti but little is known of its efficiency, i.e., what proportion of the mosquitoes encountering the trap are captured. The first version of the BGS trap was predominantly white, and the current version is mostly navy blue. While this trap is often deployed without any olfactory lure, it can also be deployed with CO2 and/or a human skin odor mimic lure to increase capture rates. We tested the efficiency of capturing Ae. aegypti under semi-field conditions for the original white version without lures as well the blue version with and without various lure combinations. None of the configurations tested here captured 100% of the mosquitoes that encountered the trap. A navy-blue trap emitting CO2 and a skin odor mimic produced the highest capture (14% of the total insects in the semi-field cage), but its capture efficiency was just 5% (of mosquitoes encountering the trap). Mosquitoes often had multiple encounters with a trap that did not result in capture; they crossed over the trap entrance without being captured or landed on the sides of the trap. Understanding these behaviors and the factors that induce them has the potential to suggest improvement in trap design and therefore capture efficiency.