bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population
Authors: Li Yuanyuan , Wang Yongfa , Zhuang Yaodong , Zhang Ping , Chen Shujiao , Asakawa Tetsuya , Gao Bizhen
Published: June 2020

Metabolomics is a promising technology for elucidating the mechanisms of metabolic syndrome (MetS). However, measurements in patients with MetS under different conditions vary. Metabolomics experiments in different populations and pathophysiological conditions are, therefore, indispensable. We performed a serum metabolomics investigation in untreated patients with MetS in the Chinese population. Untreated patients with MetS were recruited to this study. Metabolites were measured using a traditional 1H nuclear magnetic resonance (NMR) experiment followed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS‐DA). Key metabolic pathways were identified by searching the Kyoto Encyclopedia of Genes and Genomes Pathway Database. A total of 28 patients with MetS and 30 healthy subjects were enrolled. All patients were untreated because they were unaware of or neglected to treat their MetS. By 1H NMR, we identified 49 known substances. Following PCA and OPLS‐DA, 36 metabolites were confirmed to be closely associated with MetS compared with the control group; 33 metabolites were increased, whereas 3 metabolites were reduced. Importantly, 14 metabolites that changed in the serum of these untreated patients with MetS were previously unreported. Pathway analysis revealed the top 15 metabolic pathways associated with untreated MetS, which included 3 amino acid metabolic pathways. Our data suggest that untreated patients exhibit a worse pathophysiologic manifestation, which may result in more rapid progression of MetS. Thus, we propose that health education be reinforced to improve the public’s knowledge, attitude, and practice regarding MetS. The rates of “untreated” patients due to unawareness and neglect must be reduced immediately.
Increased risk of type 2 diabetes in antidepressant users: evidence from a 6‐year longitudinal study in the E3N cohort
Authors: Azevedo Da Silva M. , Fournier A. , Boutron‐Ruault M.‐C. , Balkau B. , Bonnet F. , Nabi H. , Fagherazzi G.
Published: June 2020

Aim

To examine the association between antidepressant medication use and the risk of type 2 diabetes.

Methods

Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire‐based follow‐up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional‐hazard regression models were used, with drug exposure considered as a time‐varying parameter.

Results

Of the 63 999 women who were free of drug‐treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6‐year follow‐up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non‐users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine‐type, 'other' or 'mixed' antidepressants had a 1.25‐fold (95% CI 0.99, 1.57), 1.66‐fold (95% CI 1.12, 2.46), 1.35‐fold (95% CI 1.00, 1.84) and 1.82‐fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non‐users, respectively.

Conclusion

Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).
Assessing within‐trial and across‐trial neural variability in macaque frontal eye fields and their relation to behaviour
Authors: Sendhilnathan Naveen , Basu Debaleena , Murthy Aditya
Published: June 2020

The conventional approach to understanding neural responses underlying complex computations is to study across‐trial averages of repeatedly performed computations from single neurons. When neurons perform complex computations, such as processing stimulus‐related information or movement planning, it has been repeatedly shown, through measures such as the Fano factor (FF), that neural variability across trials decreases. However, multiple neurons contribute to a common computation on a single trial, rather than a single neuron contributing to a computation across multiple trials. Therefore, at the level of a single trial, the concept of FF loses significance. Here, using a combination of simulations and empirical data, we show that changes in the spiking regularity on single trials produce changes in FF. Further, at the behavioural level, the reaction time of the animal was faster when the neural spiking regularity both within and across trials was lower. Taken together, our results provide further constraints on how changes in spiking statistics help neurons optimally encode visual and saccade‐related information across multiple timescales and its implication on behaviour.
Desiccation and cracking behaviour of clay loam subjected to different irrigation methods during wetting–drying cycles
Authors: Qi Wei , Zhang Zhan‐Yu , Wang Ce
Published: June 2020

Desiccation cracking is a common phenomenon of soil, which potentially affects irrigation and crop growth in farmland. Understanding cracking behaviour aids in developing an effective means of crack prevention or utilization. In the present paper, we report on a phenomenological investigation aimed at exploring the effects of irrigation methods on the cracking behaviour of soil during wetting–drying cycles. Nine identical specimens were prepared and subjected to three irrigation methods (surface irrigation, sprinkling irrigation and drip irrigation) and three wetting–drying cycles. Specimen cracking was monitored by a digital camera and crack patterns were delineated by geometric parameters calculated using image processing techniques. The results showed that the evaporation process of specimens could be roughly divided into three stages according to the variation of evaporation rate. Most cracks were generated during the constant rate stage, although the soil matrix zone was nearly saturated. Surface irrigation increased the cracking water content and cracking degree, in contrast to sprinkling irrigation and drip irrigation. The contribution of crack length propagation and crack width broadening to crack area growth was nearly the same when the soil water content decreased to low values. Stabilized crack networks varied from fractal regimes to uniform distribution regimes with the increasing‐length scale, and the crossover length was independent of irrigation methods and wetting–drying cycles. Under sprinkling irrigation and drip irrigation, cracks formed in the first drying remained as failure zones and most of them reappeared during subsequent drying. However, after surface irrigation most cracks did not propagate in previously cracked zones during subsequent drying, giving rise to shifting crack networks between wetting–drying cycles. Our results provide new insights regarding crack development and evolution in agricultural soil, which will be useful in crack management and irrigation arrangement during crop production.

Highlights

Effects of irrigation methods and wetting–drying cycles on cracking were investigated.

Most cracks initiate and propagate when the soil matrix zone is nearly saturated.

Different irrigation methods result in reappearing or shifting crack networks between cycles.

This study provides new insights regarding crack development and evolution in agricultural soil.
Demography, preventative healthcare and reason for relinquishment of donkeys to an equine charity in the UK (2013‐2015)
Authors: Fernandez Elena Barrio , De Blas Giral Ignacio , Thiemann Alex K. , Vázquez Bringas F. J.
Published: June 2020

Background

In the UK, there are thousands of donkeys being cared for by charities; however, little is known about the reasons for relinquishment or their previous health status, with even less information available in published literature. Such information could help to identify factors contributing to poor equine welfare and guide the development of appropriate educational resources.

Objectives

To describe the characteristics of the relinquished donkeys and to better understand the current preventative healthcare status of donkeys relinquished into The Donkey Sanctuary.

Study design

Cross‐sectional observational survey.

Methods

A total of 596 donkeys were admitted during a 30‐month period. Each had a health check at arrival; and previous management information was provided by the owner. Data were retrieved from The Donkey Sanctuary database, inputted into a specific Microsoft Access 2016 database then exported for analysis in IBM SPSS 19.0 for Windows®. Mules and ponies were excluded from the study.

Results

Many donkeys arrived without a valid passport (32.3%) or microchip (49.7%). Only 23.2% were fully protected against influenza and tetanus and 21.0% of the donkeys had no previous anthelmintic treatment history. Geriatric donkeys often suffered from moderate to severe dental disease in need of advanced treatment, and 43.9% had received no dental treatment within the last year. Overall 26.3% of donkeys were classed as overweight and 8.6% were obese. The median time since the last hoof trim was 10 weeks.

Main limitation

The health status of the studied donkeys may have been affected by the reasons for relinquishment, and associations require further investigation.

Conclusions

This study highlights the need for improving preventative healthcare in donkeys to ensure better welfare within the population.
Neuropathy‐associated histidyl‐tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish
Authors: Mullen Patrick , Abbott Jamie A. , Wellman Theresa , Aktar Mahafuza , Fjeld Christian , Demeler Borries , Ebert Alicia M. , Francklyn Christopher S.
Published: June 2020

Charcot‐Marie‐Tooth disease (CMT) encompasses a set of genetically and clinically heterogeneous neuropathies characterized by length‐dependent dysfunction of the peripheral nervous system. Mutations in over 80 diverse genes are associated with CMT, and aminoacyl‐tRNA synthetases (ARS) constitute a large gene family implicated in the disease. Despite considerable efforts to elucidate the mechanistic link between ARS mutations and the CMT phenotype, the molecular basis of the pathology is unknown. In this work, we investigated the impact of three CMT‐associated substitutions (V155G, Y330C, and R137Q) in the cytoplasmic histidyl‐tRNA synthetase (HARS1) on neurite outgrowth and peripheral nervous system development. The model systems for this work included a nerve growth factor‐stimulated neurite outgrowth model in rat pheochromocytoma cells (PC12), and a zebrafish line with GFP/red fluorescent protein reporters of sensory and motor neuron development. The expression of CMT‐HARS1 mutations led to attenuation of protein synthesis and increased phosphorylation of eIF2α in PC12 cells and was accompanied by impaired neurite and axon outgrowth in both models. Notably, these effects were phenocopied by histidinol, a HARS1 inhibitor, and cycloheximide, a protein synthesis inhibitor. The mutant proteins also formed heterodimers with wild‐type HARS1, raising the possibility that CMT‐HARS1 mutations cause disease through a dominant‐negative mechanism. Overall, these findings support the hypothesis that CMT‐HARS1 alleles exert their toxic effect in a neuronal context, and lead to dysregulated protein synthesis. These studies demonstrate the value of zebrafish as a model for studying mutant alleles associated with CMT, and for characterizing the processes that lead to peripheral nervous system dysfunction.
Binding of a negative allosteric modulator and competitive antagonist can occur simultaneously at the ionotropic glutamate receptor GluA2
Authors: Krintel Christian , Dorosz Jerzy , Larsen Andreas Haahr , Thorsen Thor Seneca , Venskutonytė Raminta , Mirza Osman , Gajhede Michael , Boesen Thomas , Kastrup Jette Sandholm
Published: June 2020

Ionotropic glutamate receptors are ligand‐gated ion channels governing neurotransmission in the central nervous system. Three major types of antagonists are known for the AMPA‐type receptor GluA2: competitive, noncompetitive (i.e., negative allosteric modulators; NAMs) used for treatment of epilepsy, and uncompetitive antagonists. We here report a 4.65 Å resolution X‐ray structure of GluA2, revealing that four molecules of the competitive antagonist ZK200775 and four molecules of the NAM GYKI53655 are capable of binding at the same time. Using negative stain electron microscopy, we show that GYKI53655 alone or ZK200775/GYKI53655 in combination predominantly results in compact receptor forms. The agonist AMPA provides a mixed population of compact and bulgy shapes of GluA2 not impacted by addition of GYKI53655. Taken together, this suggests that the two different mechanisms of antagonism that lead to channel closure are independent and that the distribution between bulgy and compact receptors primarily depends on the ligand bound in the glutamate binding site.

Database

The atomic coordinates and structure factors from the crystal structure determination have been deposited in the Protein Data Bank under accession code https://doi.org/10.2210/pdb6RUQ/pdb. The electron microscopy 3D reconstruction volumes have been deposited in EMDB (EMD‐4875: Apo; EMD‐4920: ZK200775/GYKI53655; EMD‐4921: AMPA compact; EMD‐4922: AMPA/GYKI53655 bulgy; EMD‐4923: GYKI53655; EMD‐4924: AMPA bulgy; EMD‐4925: AMPA/GYKI53655 compact).
Glimpses of oceanic lithosphere of the Challenger Deep forearc segment in the southernmost Marianas: The 143°E transect, 5800–4200 m
Authors: Stern Robert J. , Ohara Yas , Ren Minghua , Leybourne Matt , Bowers Brent
Published: June 2020

We studied nine samples of igneous rocks from the inner wall of the Mariana Trench above the Challenger Deep from 4150 to 6100 m depth recovered by manned submersible and ROV. Samples from two regions that bracket the Moho were studied: (i) 7 samples from a N‐S transect a few km to the west of the Shinkai Seep Field; and (ii) 2 samples from the Shinkai Seep Field. Transect samples include olivine‐2 pyroxene hornblendites, amphibole basalts, basaltic andesite, and hornblende andesite. We analyzed three transect samples for 40Ar/39Ar ages; two yielded good plateau ages of 46.5 ±0.5 Ma (hornblendite) and 46.60 ±0.15 Ma (hornblende andesite). These results combined with previously published results, indicate that this crust formed during an intense 46–47 Ma magmatic episode that occurred 5–6 my after subduction initiation. Hornblendites and hornblende basalts formed from primitive magmas, as shown by high MgO (11–21 wt%), Ni (222–885 ppm) and Cr (412–1145 ppm) contents. Electron microprobe analyses indicate that hornblende is Na‐rich (up to 3.0 wt% Na2O) and that many samples have an atypically large range in plagioclase composition (i.e. individual samples have An < 10 to An 90 plagioclase). Two subgroups can be identified: a mostly deeper depleted suite and a mostly shallower enriched suite. These results indicate that (i) the crust–mantle boundary in this region is transitional, occurring over a ~ 1.5 km interval, with interlayered peridotite and hornblendites between 5800 and 4300 m; and (b) extension to form the Challenger Deep forearc segment occurred by combined stretching of old crust and injection of young basaltic magmas. In contrast to the mostly fresh nature of transect samples, the two samples from the Shinaki Seep Field are intensely altered peridotite and basalt.
Carbon dioxide ameliorates reduced desquamation in dry scaly skin via protease activation
Authors: Fukagawa Satoko , Takahashi Ayami , Sayama Keimon , Mori Shinobu , Murase Takatoshi
Published: June 2020

Objective

Scaling, a phenomenon showing an abnormal detachment of the stratum corneum (SC) owing to desquamation dysfunction, is commonly observed in various skin diseases or xerotic skin due to ageing and low humidity. Therefore, it is considered that ameliorating the disturbed desquamatory process of the SC leads to improvement in scaling. Carbon dioxide (CO2) is known to be good for some skin diseases; however, the effect of CO2 on scaling and its mechanism are not sufficiently clear. We aimed to elucidate the effect of transepidermal application of CO2 on scaling and its mechanism of action.

Methods

Twenty healthy men with mild scaling on the cheeks were recruited for a double‐blind, placebo‐controlled, split‐face study. They applied the formulation containing CO2 twice daily for 1 week. After the study, the SC was collected by tape stripping to analyse desquamatory protease activities and degradation of extracellular corneodesmosomes. Furthermore, the contribution of pH to proteolysis of the corneodesmosome by CO2 was evaluated using three‐dimensional (3D) cultured epidermal models.

Results

The spectroscopic absorbance of tape strips, used as scaling indicators, was decreased, concomitantly with the amelioration of incomplete degradation of desmoglein‐1, one of the main corneodesmosomal proteins, and activation of trypsin‐like protease in the SC by transepidermal application of CO2. Experiments using 3D cultured epidermis showed that pH in the epidermal tissue was lowered by CO2, whereas a pH change was not observed with the application of the formulation containing hydrochloric acid, which was added to equalize the pH to that of the CO2 formulation.

Conclusion

The transcutaneous application of CO2 ameliorates reduced desquamatory process in xerotic skin, with concomitant mild acidification of the SC, thereby leading to improvement in scaling. Thus, CO2 may have an advantage of efficiently and safely counteracting scaling of various skin disorders.
T‐cell prolymphocytic leukemia: Review of an entity and its differential diagnostic considerations
Authors: Frater John L.
Published: June 2020

T‐cell prolymphocytic leukemia (T‐PLL) is a rare T‐cell leukemia characterized in many patients by marked peripheral lymphocytosis, prominent splenomegaly, and skin lesions. The differential diagnosis is broad and includes other T‐cell disorders presenting with similar clinical findings. This review addresses (a) the natural history, demographics, and genetic features of T‐PLL; (b) clinical and pathologic differential diagnostic considerations; and (c) recent developments in the T‐PLL literature relevant to laboratory professionals.
The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays
Authors: Exner Thomas , Rigano Joseph , Favaloro Emmanuel J.
Published: June 2020

We aimed to review the interfering effect of DOACs on tests for haemostatic function and then to discuss overcoming these with activated carbon (AC) products, thereby eliminating DOAC issues from test plasmas. Recent relevant articles were reviewed and are discussed. Laboratory tests for DOACs, lupus anticoagulant, factor assays and APC Resistance were carried out in such publications with and without an AC product on various instruments using reagents approved for diagnostic use in well‐regulated clinical laboratories. All reports on this plasma pre‐treatment by AC products agree that they extract DOACs from plasma samples with minimal effect on underlying clotting tests. The specific extraction of DOACs significantly reduced false positive lupus anticoagulant detection and provided more reliable results in clotting factor assays, APC resistance and other thrombophilia tests. Dabigatran and edoxaban seem to be adsorbed more thoroughly by AC from plasmas than rivaroxaban and apixaban. In summary, most of the AC products reviewed here appear to remove DOACs from test plasmas without significantly affecting underlying clotting tests and permit correct diagnosis of various haemostatic conditions despite the initial presence of DOACs. The application of such agents as a sample pre‐treatment to overcome the effects of DOACs for routine coagulation testing is supported by the emerging literature.
Chronic active Epstein‐Barr virus infection: A heterogeneous entity requiring a high index of suspicion for diagnosis
Authors: Ondrejka Sarah L. , Hsi Eric D.
Published: June 2020

Chronic active Epstein‐Barr virus infection of T‐ and NK‐cell type, systemic form, is a rare entity within the spectrum of EBV‐driven T‐ and NK‐cell lymphoproliferative disorders. Established diagnostic criteria and a characteristic clinical course help to differentiate it from other closely related EBV‐positive neoplasms and clinical states. We present a patient and review the natural history, pathologic features, pathogenesis, and differential diagnosis of this entity.
Genomic investigation of inherited thrombotic microangiopathy—aHUS and TTP
Authors: Enjeti Anoop K. , de Malmanche Theo , Chapman Kent , Ziolkowski Andrew
Published: June 2020

Thrombotic microangiopathies (TMA) are a heterogeneous group of red cell fragmentation syndromes characterized by a tendency for thrombosis and pathognomonic red cell fragments in peripheral blood, which results in thrombosis in the microvasculature due to endothelial damage. Genomic investigations into inherited TMAs are of diagnostic, prognostic and therapeutic value. Here, we present two cases that capture the importance of performing genomic testing in rare disorders. Treatment options for these conditions, such as plasma exchange and monoclonal antibodies against complement factors, are intensive and expensive health care interventions. The results of genomic investigation into rare TMAs can better inform the clinicians and their patients of prognosis and suitable personalized treatment options.
How I investigate neutropenia
Authors: Frater John L.
Published: June 2020

Neutropenia is a common laboratory finding in adults and children. Its underlying causes are extremely heterogeneous and include benign conditions, autoimmune disorders, infections, and malignancies. The clinical laboratory plays a central role in the diagnosis of these disorders, including data derived from hematology, microbiology, molecular biology/cytogenetics, and clinical chemistry. The purpose of this review is to (a) highlight the clinical, hematologic, and molecular genetic features of the major entities resulting in neutropenia and (b) outline an algorithm‐based approach to permit the classification of neutropenias.
Iatrogenic medication errors reported to the Victorian Poisons Information Centre
Authors: Bourke Elyssia M. , Macleod Dawson , Robinson Jeff , L. Greene Shaun
Published: June 2020

Background

Iatrogenic medication errors are a cause of medical morbidity and mortality. They result in significant cost to the Australian healthcare system each year. There is limited Australian evidence describing the iatrogenic errors occurring within the hospital system.

Aims

To examine and describe iatrogenic medication errors occurring in Victorian healthcare settings through the analysis of referrals to a state Poisons Information Centre (PIC).

Methods

A retrospective review of iatrogenic medication errors reported to the Victorian PIC (VPIC) from community and hospital healthcare settings from January 2015 to December 2019.

Results

Over a 5‐year period, 357 iatrogenic errors were identified, 63% (n = 224) of which occurred in a hospital setting. The remaining errors occurred in a community healthcare setting. One in five patients were symptomatic from the medication error at the time of the call to the VPIC, and a change in management was required in 45% (n = 165) of all cases. Five percent (n = 17) of patients developed moderate to severe clinical toxicity as determined by the recorded poisoning severity score, and 88% (n = 18) of these required critical care management. Incorrect medication dosing accounted for 62% (n = 221) of errors. Common medication dosing errors included: double dose (51%, n = 114), incorrect medication administered (14%, n = 49), incorrect route (9%, n = 31), incorrect patient (6%, n = 22) and adult dose given to a child (4%, n = 15).

Conclusions

Iatrogenic errors are occurring in the Victorian health care system. These errors can result in serious morbidity. Identification of causative factors and investment in preventative strategies will likely reduce associated morbidity and healthcare costs.
Dabigatran ameliorates airway smooth muscle remodeling in asthma by modulating Yes‐associated protein
Authors: Deng Zhenan , Xie Haojun , Cheng Weiying , Zhang Meihong , Liu Jie , Huo Yating , Liao Yulin , Cheng Yuanxiong
Published: June 2020

Accumulating evidence indicates that thrombin, the major effector of the coagulation cascade, plays an important role in the pathogenesis of asthma. Interestingly, dabigatran, a drug used in clinical anticoagulation, directly inhibits thrombin activity. The aim of this study was to investigate the effects and mechanisms of dabigatran on airway smooth muscle remodeling in vivo and in vitro. Here, we found that dabigatran attenuated inflammatory pathology, mucus production, and collagen deposition in the lungs of asthmatic mice. Additionally, dabigatran suppressed Yes‐associated protein (YAP) activation in airway smooth muscle of asthmatic mice. In human airway smooth muscle cells (HASMCs), dabigatran not only alleviated thrombin‐induced proliferation, migration and up‐regulation of collagen I, α‐SMA, CTGF and cyclin D1, but also inhibited thrombin‐induced YAP activation, while YAP activation mediated thrombin‐induced HASMCs remodeling. Mechanistically, thrombin promoted actin stress fibre polymerization through the PAR1/RhoA/ROCK/MLC2 axis to activate YAP and then interacted with SMAD2 in the nucleus to induce downstream target genes, ultimately aggravating HASMCs remodeling. Our study provides experimental evidence that dabigatran ameliorates airway smooth muscle remodeling in asthma by inhibiting YAP signalling, and dabigatran may have therapeutic potential for the treatment of asthma.
Hard and soft tissue alterations during the healing stage of immediate implant placement and provisionalization with or without connective tissue graft: A randomized clinical trial
Authors: Jiang Xi , Di Ping , Ren Shuxin , Zhang Yu , Lin Ye
Published: June 2020

Aims

To evaluate the hard and soft tissue alterations of immediately placed and provisionalized implants with or without connective tissue graft (CTG).

Materials and Methods

Single unsalvageable maxillary incisors were replaced with immediately placed and provisionalized implants in 42 participants. The patients were randomly assigned to receive simultaneous CTG (test group) and not receive CTG (control group). Digital impression and cone‐beam computed tomography images were obtained before extraction and after 6 months. Mid‐facial gingival margin migrations, soft tissue contour changes and hard tissue remodelling were analysed and compared between the two groups using three‐dimensional superimposition method.

Results

Forty participants completed the study. The test group showed significantly less buccal tissue collapse in the area 2–5 mm apical to the gingival margin. In both groups, the mid‐facial gingival margin migrated in an apico‐palatal direction and the socket void, except for a triangular space in the bucco‐coronal region, demonstrated radiographic new bone formation without statistically significant differences.

Conclusions

The CTG used with immediate implant placement and provisionalization could compensate for the facial tissue collapse, but it did not benefit maintenance of the mid‐facial gingival margin position during the 6‐month follow‐up. New bone formation observed radiographically can be expected in most areas of the socket void, regardless of CTG use (ChiCTR‐1900028494).
Changes in, and predictors of, quality of life among patients with unstable angina after percutaneous coronary intervention
Authors: Van Nguyen Huy , Khuong Long Quynh , Nguyen Anh Tuan , Nguyen Anh Le Tuan , Nguyen Cham Thi , Nguyen Ha Thi Thu , Tran Thu Thi Ha , Dao An Thi Minh , Gilmour Stuart , Van Hoang Minh
Published: June 2020

Rationale, aims and objectives

Changes in, and predictors of, quality of life (QoL) among unstable angina patients are informative for both clinical and public health practice. However, there is little research on this topic, especially in health care settings with limited resources. This study aims to detect changes in QoL and its associated factors among patients with unstable angina after percutaneous coronary intervention.

Methods

A longitudinal design was conducted with two repeated rounds of measurements, 1 and 3 months after intervention, using the generic SF‐36 questionnaire, in 120 patients from Vietnam National Heart Institute. A linear mixed‐effects model was used to assess changes in patient QoL over time while adjusting for other covariates.

Results

Only two out of eight QoL subscales (social functioning and emotional well‐being) declined after 1 month, but these tended to rise again after 3 months, while scores of all other QoL subscales increased. Adjusting for covariates, QoL increased slightly after 1 month of intervention (β = 0.65, 95%CI = −0.86 to 2.16) but improved by almost six QoL points after 3 months (β = 5.99, 95%CI = 4.48 to 7.50). Four confounders significantly associated with a decline in QoL were older age, being retired, living in rural areas, and having abnormal troponin level.

Conclusion

QoL of the patients with unstable angina improves significantly 3 months after intervention, rather than after 1 month. More attention should be given to patients, who are old, retired, live in rural areas and have abnormal troponin level.
Effects of Pseudoloma neurophilia infection on the brain transcriptome in zebrafish (Danio rerio)
Authors: Midttun Helene L.E. , Vindas Marco A. , Whatmore Paul J , Øverli Øyvind , Johansen Ida B.
Published: June 2020

Laboratory zebrafish are commonly infected with the intracellular, brain‐infecting microsporidian parasite Pseudoloma neurophilia. Chronic P. neurophilia infections induce inflammation in meninges, brain and spinal cord, and have been suggested to affect neural functions since parasite clusters reside inside neurons. However, underlying neural and immunological mechanisms associated with infection have not been explored. Utilizing RNA‐sequencing analysis, we found that P. neurophilia infection upregulated 175 and downregulated 45 genes in the zebrafish brain, compared to uninfected controls. Four biological pathways were enriched by the parasite, all of which were associated with immune function. In addition, 14 gene ontology (GO) terms were enriched, eight of which were associated with immune responses and five with circadian rhythm. Surprisingly, no differentially expressed genes or enriched pathways were specific for nervous system function. Upregulated immune‐related genes indicate that the host generally show a pro‐inflammatory immune response to infection. On the other hand, we found a general downregulation of immune response genes associated with anti‐pathogen functions, suggesting an immune evasion strategy by the parasite. The results reported here provide important information on host–parasite interaction and highlight possible pathways for complex effects of parasite infections on zebrafish phenotypes.
Risk management in community pharmacy practice in Abu Dhabi Region: a cross-sectional study
Authors: Abu Hagar Reham , El-Dahiyat Faris , El Refae Ghaleb
Published: June 2020

Objectives

Pharmacy risk factors impose a major threat to general healthcare outcomes. Risks that can directly affect patients are known as clinical risk factors, and other, non-clinical risk factors may also affect a pharmacist's performance and pharmaceutical profession. This study aims to evaluate the risks, which occur in community pharmacies in Abu Dhabi, and to investigate the protective plans followed in such incidence.

Methods

A self-administrated online questionnaire was distributed to community pharmacists in Abu Dhabi. The questionnaire items were tested by content and face validity in a panel of experts and pilot study. The Statistical Package for the Social Sciences (SPSS) program was used for the data analysis.

Key findings

Medication errors and computer system malfunction occur monthly, as reported by 40% of the participants (n = 131). Theft cases were reported by 37.6% (n = 121) of the pharmacists. Violence was categorized as verbal, psychological and physical abuse, and the frequency was 56.8% (n = 183), 30.4% (n = 98) and 14.3% (n = 46) respectively. Almost all the participants belief that communication skills, alertness and experience are the most important internal factors affecting performance. Environmental factors such as the availability of restrooms were cited as important external factors enhancing performance. Chain pharmacies were found to address electrical failure and dealing with look-alike sound-alike/high-alert medication efficiently.

Conclusions

Different types of clinical and non-clinical risk in pharmacy practice were identified, and risk mitigation techniques were proposed. A positive attitude of community pharmacists was observed towards identifies risks and on the suggested mitigation techniques. It is necessary to publish a universally referenced validated risk factor list for evaluating current risk management plans to maintain safe pharmacy practices and include management courses within pharmacy curriculum.
In vitro metabolism of red clover isoflavones in rumen fluid
Authors: Dadáková Kateřina , Trnková Andrea , Kašparovská Jitka , Křížová Ludmila , Lochman Jan , Kašparovský Tomáš
Published: June 2020

The degradation of red clover isoflavones was studied in vitro using a rumen fluid buffer system. Various amounts of red clover extract (5–75 mg) together with hay or concentrate‐rich diet were added to 40 ml of rumen fluid obtained from non‐lactating and lactating dairy cows, respectively, and incubated for 0, 3, 6, 12 or 24 hr. Following incubation, concentrations of daidzein, genistein, formononetin, biochanin A and equol were determined in the samples. After 3 hr of incubation, isoflavone metabolism and equol production could be observed. The results obtained indicate that hay diet provides better conditions for isoflavone metabolism, as concentrations of daidzein, formononetin and biochanin A were higher in incubations based on the concentrate‐rich diet and the production of equol was higher in incubations based on the hay diet. Furthermore, in incubations with higher amounts of added clover extract, a decrease in equol production was observed. Further studies are needed to clarify the role of adaptation of rumen microflora on isoflavone degradation kinetics and to clarify the interrelationship between various dietary factors, rumen microbiota and isoflavones. The knowledge of isoflavone metabolism kinetics in dependence on studied factors will be useful for the optimization of feeding dose.
Spatial Disparities in Coronavirus Incidence and Mortality in the United States: An Ecological Analysis as of May 2020
Authors: Zhang Charlie H. , Schwartz Gary G.
Published: June 2020

Purpose

This ecological analysis investigates the spatial patterns of the COVID‐19 epidemic in the United States in relation to socioeconomic variables that characterize US counties.

Methods

Data on confirmed cases and deaths from COVID‐19 for 2,814 US counties were obtained from Johns Hopkins University. We used Geographic Information Systems (GIS) to map the spatial aspects of this pandemic and investigate the disparities between metropolitan and nonmetropolitan communities. Multiple regression models were used to explore the contextual risk factors of infections and death across US counties. We included population density, percent of population aged 65+, percent population in poverty, percent minority population, and percent of the uninsured as independent variables. A state‐level measure of the percent of the population that has been tested for COVID‐19 was used to control for the impact of testing.

Findings

The impact of COVID‐19 in the United States has been extremely uneven. Although densely populated large cities and their surrounding metropolitan areas are hotspots of the pandemic, it is counterintuitive that incidence and mortality rates in some small cities and nonmetropolitan counties approximate those in epicenters such as New York City. Regression analyses support the hypotheses of positive correlations between COVID‐19 incidence and mortality rates and socioeconomic factors including population density, proportions of elderly residents, poverty, and percent population tested.

Conclusions

Knowledge about the spatial aspects of the COVID‐19 epidemic and its socioeconomic correlates can inform first responders and government efforts. Directives for social distancing and to “shelter‐in‐place” should continue to stem the spread of COVID‐19.
A term structure model for dividends and interest rates
Authors: Filipović Damir , Willems Sander
Published: June 2020

Over the last decade, dividends have become a standalone asset class instead of a mere side product of an equity investment. We introduce a framework based on polynomial jump‐diffusions to jointly price the term structures of dividends and interest rates. Prices for dividend futures, bonds, and the dividend paying stock are given in closed form. We present an efficient moment based approximation method for option pricing. In a calibration exercise we show that a parsimonious model specification has a good fit with Euribor interest rate swaps and swaptions, Euro Stoxx 50 Index dividend futures and dividend options, and Euro Stoxx 50 Index options.
The nine stages of skin‐to‐skin: practical guidelines and insights from four countries
Authors: Brimdyr Kajsa , Cadwell Karin , Svensson Kristin , Takahashi Yuki , Nissen Eva , Widström Ann‐Marie
Published: June 2020

Incorporating systematic evidence with clinical expertise is a key element in the quest to improve quality of care and patient outcomes. The evidence supporting skin‐to‐skin contact in the first hour after birth is robust and includes significantly improved outcomes for both mother and infant. This paper compares available iterative data about newborn behaviour in the first hour after birth to further describe the observable behaviour pattern and to provide clinical insight for further research. Although the evidence for positive outcomes through skin‐to‐skin contact are robust, there is a dearth of research specifically focused on clinical practice. The methodology considers the four available data sets that used Widström's 9 stages, which consists of studies from Japan, Sweden, Italy and the United States, examining the parameters of each stage across settings from around the world. This research provides an expanded understanding of the timing of the newborn's progression through Widström's 9 observable stages. We found that newborns in all four data sets began with a birth cry and continued through the remaining stages of relaxation, awakening, activity, rest, crawling, familiarization, suckling and sleeping during the first hours after birth and consolidated the data into a Sign of the Stages chart to assist in further research. The evidence supports making a safe space and time for this important newborn behaviour. Clinical practices should encourage and protect this sensitive period.
Quaternary land bridges have not been universal conduits of gene flow
Authors: Cros Emilie , Chattopadhyay Balaji , Garg Kritika M. , Ng Nathaniel S. R. , Tomassi Suzanne , Benedick Suzan , Edwards David P. , Rheindt Frank E.
Published: June 2020

Quaternary climate oscillations are a well‐known driver of animal diversification, but their effects are most well studied in areas where glaciations lead to habitat fragmentation. In large areas of the planet, however, glaciations have had the opposite effect, but here their impacts are much less well understood. This is especially true in Southeast Asia, where cyclical changes in land distribution have generated enormous land expansions during glacial periods. In this study, we selected a panel of five songbird species complexes covering a range of ecological specificities to investigate the effects Quaternary land bridges have had on the connectivity of Southeast Asian forest biota. Specifically, we combined morphological and bioacoustic analysis with an arsenal of population genomic and modelling approaches applied to thousands of genome‐wide DNA markers across a total of more than 100 individuals. Our analyses show that species dependent on forest understorey exhibit deep differentiation between Borneo and western Sundaland, with no evidence of gene flow during the land bridges accompanying the last 1–2 ice ages. In contrast, dispersive canopy species and habitat generalists have experienced more recent gene flow. Our results argue that there remains much cryptic species‐level diversity to be discovered in Southeast Asia even in well‐known animal groups such as birds, especially in nondispersive forest understorey inhabitants. We also demonstrate that Quaternary land bridges have not been equally suitable conduits of gene flow for all species complexes and that life history is a major factor in predicting relative population divergence time across Quaternary climate fluctuations.
Herbicides as anthropogenic drivers of eco‐evo feedbacks in plant communities at the agro‐ecological interface
Authors: Iriart Veronica , Baucom Regina S. , Ashman Tia‐Lynn
Published: June 2020

Herbicides act as human‐mediated novel selective agents and community disruptors, yet their full effects on eco‐evolutionary dynamics in natural communities have only begun to be appreciated. Here, we synthesize how herbicide exposures can result in dramatic phenotypic and compositional shifts within communities at the agro‐ecological interface and how these in turn affect species interactions and drive plant (and plant‐associates') evolution in ways that can feedback to continue to affect the ecology and ecosystem functions of these assemblages. We advocate a holistic approach to understanding these dynamics that includes plastic changes and plant community transformations and also extends beyond this single trophic level targeted by herbicides to the effects on nontarget plant‐associated organisms and their potential to evolve, thereby embracing the complexity of these real‐world systems. We make explicit recommendations for future research to achieve this goal and specifically address impacts of ecology on evolution, evolution on ecology and their feedbacks so that we can gain a more predictive view of the fates of herbicide‐impacted communities.
A new mode of NPR1 action via an NB‐ARC–NPR1 fusion protein negatively regulates the defence response in wheat to stem rust pathogen
Authors: Wang Xiaojing , Zhang Hongtao , Nyamesorto Bernard , Luo Yi , Mu Xiaoqian , Wang Fangyan , Kang Zhensheng , Lagudah Evans , Huang Li
Published: June 2020

NPR1 has been found to be a key transcriptional regulator in some plant defence responses. There are nine NPR1 homologues (TaNPR1) in wheat, but little research has been done to understand the function of those NPR1‐like genes in the wheat defence response against stem rust (Puccinia graminis f. sp. tritici) pathogens.

We used bioinformatics and reverse genetics approaches to study the expression and function of each TaNPR1.

We found six members of TaNPR1 located on homoeologous group 3 chromosomes (designated as TaG3NPR1) and three on homoeologous group 7 chromosomes (designated as TaG7NPR1). The group 3 NPR1 proteins regulate transcription of SA‐responsive PR genes. Downregulation of all the TaNPR1 homologues via virus‐induced gene co‐silencing resulted in enhanced resistance to stem rust. More specifically downregulating TaG7NPR1 homeologues or Ta7ANPR1 expression resulted in stem rust resistance phenotype. By contrast, knocking down TaG3NPR1 alone did not show visible phenotypic changes in response to the rust pathogen. Knocking out Ta7ANPR1 enhanced resistance to stem rust. The Ta7ANPR1 locus is alternatively spliced under pathogen inoculated conditions.

We discovered a new mode of NPR1 action in wheat at the Ta7ANPR1 locus through an NB‐ARC–NPR1 fusion protein negatively regulating the defence to stem rust infection.
The enigma of life: confronting marvels at the edges of science
Authors: Paulson Steve , Gleiser Marcelo , Lombrozo Tania , Francis Gavin
Published: June 2020

Einstein famously claimed that “the most incomprehensible thing about the universe is that it is comprehensible.” This statement suggests that no amount of scientific explanation will suffice to make sense of the bizarre situation of the human mind within the universe. So what are the actual roles of awe and wonder within the framework of contemporary science? How, for instance, do awe and wonder inform scientists’ understanding of the phenomena they are researching? What aspects of contemporary science are more likely to elicit wonder, and why? Is science rechanneling our innate thirst for knowledge and understanding toward more concrete and palpable realities, or is it aggravating the tension between truth and meaning by revealing the scope of our ignorance when it comes to probing the ultimate nature of reality? Physicist Marcelo Gleiser, experimental psychologist Tania Lombrozo, and physician Gavin Francis analyze the impact of awe and wonder on their own work and on the mindsets of their colleagues carrying out leading‐edge scientific research.
Allometric co‐variation of xylem and stomata across diverse woody seedlings
Authors: Zhong Mengying , Cerabolini Bruno E. L. , Castro‐Díez Pilar , Puyravaud Jean‐Philippe , Cornelissen Johannes H. C.
Published: June 2020

Leaf stomatal density is known to co‐vary with leaf vein density. However, the functional underpinning of this relation, and how it scales to whole‐plant water transport anatomy, is still unresolved. We hypothesized that the balance of water exchange between the vapour phase (in stomata) and liquid phase (in vessels) depends on the consistent scaling between the summed stomatal areas and xylem cross‐sectional areas, both at the whole‐plant and single‐leaf level. This predicted size co‐variation should be driven by the co‐variation of numbers of stomata and terminal vessels. We examined the relationships of stomatal traits and xylem anatomical traits from the entire plant to individual leaves across seedlings of 53 European woody angiosperm species. There was strong and convergent scaling between total stomatal area and stem xylem area per plant and between leaf total stomatal area and midvein xylem area per leaf across all the species, irrespective of variation in leaf habit, growth‐form or relative growth rate. Moreover, strong scaling was found between stomatal number and terminal vessel number, whereas not in their respective average areas. Our findings have broad implications for integrating xylem architecture and stomatal distribution and deepen our understanding of the design rules of plants' water transport network.
Reactivation of Kasabach‐Merritt phenomenon in a young adult with a congenital kaposiform hemangioendothelioma
Authors: Ivars Marta , Triana Paloma , López‐Gutiérrez Juan Carlos
Published: June 2020

We present the rare case of a young adult who developed late recurrence of Kasabach‐Merritt phenomenon in a congenital kaposiform hemangioendothelioma that had been quiescent since infancy. We postulate that the extensive and infiltrative nature of our patient's tumor, combined with a recent history of direct microtrauma from acupuncture, contributed to the development of this late complication.