bluuebunny/crossref_metadata_2025 huggingface dataset:
Autism‐related behaviors in the cyclooxygenase‐2‐deficient mouse model
Authors: Wong Christine T. , Bestard‐Lorigados Isabel , Crawford Dorota A.
Published: July 2018

Prostaglandin E2 (PGE2) is an endogenous lipid molecule involved in normal brain development. Cyclooxygenase‐2 (COX2) is the main regulator of PGE2 synthesis. Emerging clinical and molecular research provides compelling evidence that abnormal COX2/PGE2 signaling is associated with autism spectrum disorder (ASD). We previously found that COX2 knockout mice had dysregulated expression of many ASD genes belonging to important biological pathways for neurodevelopment. The present study is the first to show the connection between irregular COX2/PGE2 signaling and autism‐related behaviors in male and female COX2‐deficient knockin, (COX)‐2−, mice at young (4‐6 weeks) or adult (8‐11 weeks) ages. Autism‐related behaviors were prominent in male (COX)‐2− mice for most behavioral tests. In the open field test, (COX)‐2− mice traveled more than controls and adult male (COX)‐2− mice spent less time in the center indicating elevated hyperactive and anxiety‐linked behaviors. (COX)‐2− mice also buried more marbles, with males burying more than females, suggesting increased anxiety and repetitive behaviors. Young male (COX)‐2− mice fell more frequently in the inverted screen test revealing motor deficits. The three‐chamber sociability test found that adult female (COX)‐2− mice spent less time in the novel mouse chamber indicative of social abnormalities. In addition, male (COX)‐2− mice showed altered expression of several autism‐linked genes: Wnt2, Glo1, Grm5 and Mmp9. Overall, our findings offer new insight into the involvement of disrupted COX2/PGE2 signaling in ASD pathology with age‐related differences and greater impact on males. We propose that (COX)‐2− mice might serve as a novel model system to study specific types of autism.
Secretion and fusion of biogeochemically active archaeal membrane vesicles
Authors: Johnson Tyler B. , Mach Collin , Grove Ryan , Kelly Robert , Van Cott Kevin , Blum Paul
Published: July 2018

Microbes belonging to the genus Metallosphaera oxidize sulfidic minerals. These organisms thrive at temperature extremes and are members of the archaeal phylum Crenarchaeota. Because they can employ a lithoautotrophic metabolism, energy availability likely limits their activity raising questions about how they conduct biogeochemical activity. Vesicles are membrane encapsulated structures produced by all biological lineages but using very different mechanisms. Across the Crenarchaeota, it has been proposed that a eukaryotic‐like Endosomal Sorting Complex Required for Transport system promotes formation of these structures but in response to unknown signals and for undefined purposes. To address such questions, Metallosphaera sedula vesicle formation and function were studied under lithoautotrophic conditions. Energy deprivation was evaluated and found to stimulate vesicle synthesis while energy excess repressed vesicle formation. Purified vesicles adhered rapidly to the primary copper ore, chalcopyrite, and formed compact monolayers. These vesicle monolayers catalyzed iron oxidation and solubilization of mineralized copper in a time‐dependent process. As these activities were membrane associated, their potential transfer by vesicle fusion to M. sedula cells was examined. Fluorophore‐loaded vesicles rapidly transferred fluorescence under environmentally relevant conditions. Vesicles from a related archaeal species were also capable of fusion; however, this process was species‐specific as vesicles from different species were incapable of fusion. In addition, vesicles produced by a copper‐resistant M. sedula cell line transferred copper extrusion capacity along with improved viability over mutant M. sedula cells lacking copper transport proteins. Membrane vesicles may therefore play a role in modulating energy‐related traits in geochemical environments by fusion‐mediated protein delivery.
Improvement in clinical outcomes and replacement factor VIII use in patients with haemophilia A after factor VIII pharmacokinetic‐guided prophylaxis based on Bayesian models with myPKFiT®
Authors: Mingot‐Castellano M. E. , Parra R. , Núñez R. , Martorell M.
Published: July 2018

Objectives

Patients with severe haemophilia A (HA) receive factor VIII (FVIII) replacement therapy as prophylaxis. myPKFiT®is an online medical application that allows authorized users to simulate dosing regimens with patient pharmacokinetic (PK) profiles based on only 2 blood samples. Our aim was to assess the impact of using this medical device in routine practice in terms of FVIII consumption and clinical outcomes.

Methods

Thirty‐six patients with severe HA on prophylaxis with Advate® were recruited in 3 centres in Spain. Annual bleeding rate (ABR), annual joint bleeding rate (AJBR) and annual FVIII consumption before and after adjustment were obtained using the patient’s clinical history (12 months before) and prospectively recorded data (12 months after), respectively. Adjustment was based on PK parameters provided by myPKFiT®, joint status and relative risk associated with physical activity and bleeding phenotype.

Results

ABR and AJBR were significantly reduced after adjustment in the overall sample (−2.2 ± 1.3, P = .018 and −1.9 ± 1.2, P = .012, respectively) and in patients aged >15 years (−2.6 ± 1.4, P = .011 and −2.0 ± 1.2, P = .005, respectively). Adjustment had an effect on the individual FVIII consumption of most patients: annual amount was reduced in 18 cases and increased in 14. There was no significant effect on the mean amount (198 784 ± 110 387) compared to that used the year prior to myPKFiT®‐adjusted prophylaxis (199 466 ± 103 670; P = .737).

Discussion

Our results suggest that PK‐guided prophylaxis using myPKFiT® improved clinical outcomes and optimized FVIII consumption in the study population. This personalized approach may reduce bleeding rates without significantly increasing the overall cost of FVIII therapy.
Clinical management of Anti‐TNF‐alpha‐induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review
Authors: Melo Francisco J. , Magina Sofia
Published: July 2018

Tumor necrosis factor alpha inhibitors (anti‐TNF‐α) completely revolutionized the treatment of inflammatory bowel disease (IBD). However, anti‐TNF‐α‐induced cutaneous side effects have been increasingly reported in the literature. Particularly, psoriasis and the recently recognized psoriasiform lesions are of particular concern, as anti‐TNF‐α agents are also used in the treatment of psoriasis, seemingly reflecting an immunological paradox. The clinical management of these cutaneous lesions is particularly challenging, owing to the potential need of anti‐TNF‐α discontinuation and scarcity of other therapeutic options. Therefore, optimization of current topical and systemic therapies and incorporation of new therapeutic agents is of great interest. Our aim is to review data in the literature regarding the clinical management of these cutaneous lesions and provide a therapeutic algorithm, supported by our experience as a tertiary referral center for IBD. Although in older reports no distinction was made, anti‐TNF‐α‐induced psoriasiform lesions are not only more prevalent but also bear notable differences from classical psoriasis, possibly reflecting a different nosological entity. Onset of lesions has been related to periods of IBD remission, as supported by low levels of fecal calprotectin. Psoriasiform lesions can be adequately managed either by topical (glucocorticoids, calcineurin inhibitors, and antibiotics) or systemic (phototherapy, acitretin, glucocorticoids, and antibiotics) therapies and/or switch to other anti‐TNF‐α agents. Data referring to patients who were able to continue on the same IBD therapy ranged from 30.7 to 100%, reinforcing the importance of an adequate control of these lesions. The recently approved ustekinumab offers another step in the management of anti‐TNF‐α‐intolerant patients.
The information environment of the firm and the market valuation of R&D
Authors: Zhang Lu Y. , Toffanin Melissa
Published: July 2018

We examine whether firms’ information environment influences the market valuation of their hard‐to‐value knowledge assets: R&D capital. We find that a better information environment, as measured by greater analyst coverage, lower earnings forecast dispersion, and greater earnings forecasting accuracy, is associated with higher stock market valuation of firms’ R&D capital. We conduct additional analyses to rule out alternative explanations and test for the direction of causality. Our causal evidence suggests that analysts significantly reduce the information uncertainty surrounding firms’ R&D capital.
Perceptions, knowledge, and perceived barriers of Yemeni pharmacists and pharmacy technicians towards evidence‐based practice
Authors: Al‐Jamei Sayida , Abu Farha Rana , Zawiah Mohammed , Kadi Taha , Al‐Sonidar Afnan
Published: July 2018

Rational, aims, and objective

The aim of this study was to assess the knowledge and perception towards evidence‐based practice (EBP) and identify the perceived barriers to practicing EBP among Yemeni pharmacists and pharmacy technicians.

Methods

A cross‐sectional survey study was carried out among 153 Yemeni pharmacists and pharmacy technicians who are working in hospitals or community pharmacies. This study took place between the 15th of August and the 8th of November 2017 using a self‐administered validated questionnaire. The study was approved by the ethics committee/scientific research center of Yemen University, Yemen (Reference number: ERC/2017/103).

Results

Completed questionnaires were received from 153 (46.6% response rate). Most of the respondents showed a positive attitude towards EBP; however, their understanding of the basic terms used in EBP was poor (34.6%). The types of source that the respondent used in high percentage to make their decisions were own judgement and consulting the colleagues that can no longer be accurate and evidence based. The barriers to practicing EBP identified by most respondents were the limited access to EBP sources and lack of personal time.

Conclusion

These results reveal strong support for EBP among pharmacists and pharmacy technicians in Yemen but only a minority indicated that they understood the technical terms of EBP. Training and continuing education programs on EBP and guidelines for pharmacists are strongly needed. These findings may help in planning the use and the application of EBP process in pharmacy practice.
Distribution and prevalence of T. bryosalmonae in Austria: A first survey of trout from rivers with a shrinking population
Authors: Lewisch Eva , Unfer Guenther , Pinter Kurt , Bechter Thomas , El‐Matbouli Mansour
Published: July 2018

The first evidence of proliferative kidney disease (PKD) in an Austrian river (the River Kamp) was documented in 2016, and no information on the PKD infection status of trout in other rivers was available. Since then, brown trout (Salmo trutta fario) and rainbow trout (Oncorhynchus mykiss) have been collected from rivers in Upper and Lower Austria for different diagnostic purposes. In this study, we summarize the recent findings of a first survey concerning the distribution of Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease (PKD), from these samples. Between September 2015 and October 2017, a total of 280 brown trout and 39 rainbow trout were collected from 21 rivers in the provinces of Upper and Lower Austria. T. bryosalmonae was detected by PCR of kidney tissue in 17 of 21 sampled rivers and in 138 of 280 brown trout as well as in 11 of 39 rainbow trout. Pathological signs of PKD (e.g., hypertrophy of the kidney) were observed in 33 analysed brown trout and six rainbow trout samples. No correlations between fish infected by T. bryosalmonae and the parameters size and age class, condition factor, geological origin of the streams and distribution within the river course were found, while positively tested fish are significantly increased at sampling sites exceeding water temperatures of 15°C for median periods of 115 days. The prevalence within the affected streams or stream sections is highly variable, and in single rivers, infection rates of up to 90% are confirmed.
Betanodavirus infection in bath‐challenged Solea senegalensis juveniles: A comparative analysis of RGNNV, SJNNV and reassortant strains
Authors: Souto Sandra , Olveira José G. , Alonso M. Carmen , Dopazo Carlos P. , Bandín Isabel
Published: July 2018

Senegalese sole has been shown to be highly susceptible to betanodavirus infection, although virulence differences were observed between strains. To study the mechanisms involved in these differences, we have analysed the replication in brain tissue of three strains with different genotypes during 15 days after bath infection. In addition, possible portals of entry for betanodavirus into sole were investigated. The reassortant RGNNV/SJNNV and the SJNNV strain reached the brain after 1 and 2 days postinfection, respectively. Although no RGNNV replication was detected until day 3–4 postinfection, at the end of the experiment this strain yielded the highest viral load; this is in accordance with previous studies in which sole infected with the reassortant showed more acute signs and earlier mortality than the RGNNV and SJNNV strains. Differences between strains were also observed in the possible portals of entry. Thus, whereas the reassortant strain could infect sole mainly through the skin or the oral route, and, to a minor extent, through the gills, the SJNNV strain seems to enter fish only through the gills and the RGNNV strain could use all tissues indistinctly. Taken together, all these results support the hypothesis that reassortment has improved betanodavirus infectivity for sole.
Phase equilibrium modelling and implications forP–Tdeterminations of medium‐temperature UHP eclogites, North Qaidam terrane, China
Authors: Hernández‐Uribe David , Mattinson Chris G. , Zhang Jianxin
Published: July 2018

In contrast to low‐Teclogites (garnet growth zoning preserved) or high‐Teclogites (garnet diffusionally homogenized at peak conditions), medium‐temperature eclogites pose additional challenges toP–Tdeterminations due to the partial preservation of garnet zoning. The Dulan area, in the southeastern part of North Qaidam ultrahigh‐pressure terrane, exposes minor eclogites hosted by ortho‐ and paragneisses. Four fresh, medium‐temperature eclogites contain the paragenesis Grt+Omp+Rt+Qz/Coe+Ph±Ky±Zo. In all samples, garnetXMgshows little zoning, suggesting diffusional modification, and precludes the use of pyrope+almandine+grossular isopleth intersections to determine aP–Tpath. However, in one sample, sharp zoning in grossular content suggests that grossular growth compositions are preserved. Since garnet pyrope+almandine compositions appear to be modified, we instead use the intersections of grossular and garnet volume isopleths to define a progradeP–Tpath. This approach yields a path from ~17 kbar and ~410°C to ~35 kbar and ~625°C with a gradient of ~5–9°C/km through the lawsonite stability field. PeakP–Tconditions determined from the intersection between Si pfu in phengite and Zr‐in‐rutile isopleths are ~26–33 kbar and ~625–700 °C for the four eclogites. These conditions are close to the limit of the lawsonite stability field, suggesting that fluid released from lawsonite breakdown may have promoted re‐equilibration at these conditions. These peak conditions are also in good agreement (within 3 kbar and 50°C) with garnet–omphacite–phengite (±kyanite) thermobarometry in three of the four samples. We regard the phengite–rutile constraints as more reliable, because they are less sensitive to uncertainties associated with ferric iron compared to conventional thermobarometry. Phase equilibrium modelling predicts that the retrograde assemblage of amphibole+zoisite formed at ~60 km. Infiltration of external fluids was likely required for the growth of these hydrous minerals. Based on the comparison ofP–Testimation methods applied in this study, we propose that the garnet grossular+volume isopleths can recover the progradeP–Tpath of medium‐temperature eclogites, and that the combination of phengite+rutile isopleths represents a more robust approach to constrain peakP–Tconditions.
High‐density lipoprotein mimetic peptide 4F mitigates amyloid‐β‐induced inhibition of apolipoprotein E secretion and lipidation in primary astrocytes and microglia
Authors: Chernick Dustin , Ortiz‐Valle Stephanie , Jeong Angela , Swaminathan Suresh K. , Kandimalla Karunya K. , Rebeck G. William , Li Ling
Published: July 2018

The apolipoprotein E (apoE) ε4 allele is the primary genetic risk factor for late‐onset Alzheimer's disease (AD). ApoE in the brain is produced primarily by astrocytes; once secreted from these cells, apoE binds lipids and forms high‐density lipoprotein (HDL)‐like particles. Accumulation of amyloid‐β protein (Aβ) in the brain is a key hallmark of AD, and is thought to initiate a pathogenic cascade leading to neurodegeneration and dementia. The level and lipidation state of apoE affect Aβ aggregation and clearance pathways. Elevated levels of plasma HDL are associated with lower risk and severity of AD; the underlying mechanisms, however, have not been fully elucidated. This study was designed to investigate the impact of an HDL mimetic peptide, 4F, on the secretion and lipidation of apoE. We found that 4F significantly increases apoE secretion and lipidation in primary human astrocytes as well as in primary mouse astrocytes and microglia. Aggregated Aβ inhibits glial apoE secretion and lipidation, causing accumulation of intracellular apoE, an effect that is counteracted by co‐treatment with 4F. Pharmacological and gene editing approaches show that 4F mediates its effects partially through the secretory pathway from the endoplasmic reticulum to the Golgi apparatus and requires the lipid transporter ATP‐binding cassette transporter A1. We conclude that the HDL mimetic peptide 4F promotes glial apoE secretion and lipidation and mitigates the detrimental effects of Aβ on proper cellular trafficking and functionality of apoE. These findings suggest that treatment with such an HDL mimetic peptide may provide therapeutic benefit in AD.

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Read the Editorial Highlight for this article on page 580.
Structure of monomeric full‐length ARC sheds light on molecular flexibility, protein interactions, and functional modalities
Authors: Hallin Erik I. , Eriksen Maria S. , Baryshnikov Sergei , Nikolaienko Oleksii , Grødem Sverre , Hosokawa Tomohisa , Hayashi Yasunori , Bramham Clive R. , Kursula Petri
Published: July 2018

The activity‐regulated cytoskeleton‐associated protein (ARC) is critical for long‐term synaptic plasticity and memory formation. Acting as a protein interaction hub, ARC regulates diverse signalling events in postsynaptic neurons. A protein interaction site is present in the ARC C‐terminal domain (CTD), a bilobar structure homologous to the retroviral Gag capsid domain. We hypothesized that detailed knowledge of the three‐dimensional molecular structure of monomeric full‐length ARC is crucial to understand its function; therefore, we set out to determine the structure of ARC to understand its various functional modalities. We purified recombinant ARC and analyzed its structure using small‐angle X‐ray scattering and synchrotron radiation circular dichroism spectroscopy. Monomeric full‐length ARC has a compact, closed structure, in which the oppositely charged N‐terminal domain (NTD) and CTD are juxtaposed, and the flexible linker between them is not extended. The modeled structure of ARC is supported by intramolecular live‐cell Förster resonance energy transfer imaging in rat hippocampal slices. Peptides from several postsynaptic proteins, including stargazin, bind to the N‐lobe, but not to the C‐lobe, of the bilobar CTD. This interaction does not induce large‐scale conformational changes in the CTD or flanking unfolded regions. The ARC NTD contains long helices, predicted to form an anti‐parallel coiled coil; binding of ARC to phospholipid membranes requires the NTD. Our data support a role for the ARC NTD in oligomerization as well as lipid membrane binding. The findings have important implications for the structural organization of ARC with respect to distinct functions, such as postsynaptic signal transduction and virus‐like capsid formation.

Open Practices

Open Science: This manuscript was awarded with the Open Materials Badge.

For more information see: https://cos.io/our-services/open-science-badges/

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Adult neurogenesis and its role in brain injury and psychiatric diseases
Authors: Hayashi Yoshitaka , Jinnou Hideo , Sawamoto Kazunobu , Hitoshi Seiji
Published: July 2018

In the adult mammalian brain, neural stem cells (NSCs) reside in two neurogenic regions, the walls of the lateral ventricles, and the subgranular zone of the hippocampus, which generate new neurons for the olfactory bulb and dentate gyrus, respectively. These adult NSCs retain their self‐renewal ability and capacity to differentiate into neurons and glia as demonstrated by in vitro studies. However, their contribution to tissue repair in disease and injury is limited, lending credence to the claim by prominent neuropathologist Ramón y Cajal that ‘once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably’. However, recent progress toward understanding the fundamental biology of adult NSCs and their role in pathological conditions has provided new insight into the potential therapeutic utility of endogenous NSCs. In this short review, we highlight two topics: the altered behavior of NSCs after brain damage and the dysfunction of NSCs and oligodendrocyte precursor cells, another type of undifferentiated cell in the adult brain, in mood affective disorders.

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The Influence of Age, Gender, Mandibular Bone Height, Previous Experience with Prostheses, and Fabrication Methods on Masticatory Performance of Complete Denture Wearers
Authors: Alves Carla Pinto , Munhoz Maira Foresti Vieira , Oliveira Nascimento Gabriela Mayara , Nícoli Giovanni Antônio , Paleari André Gustavo , Camargos Germana de Villa
Published: July 2018

Purpose

To evaluate the influence of age, gender, mandibular bone height, previous experience with prostheses, and methods for denture fabrication on masticatory performance of complete denture (CD) wearers.

Materials and Methods

For this study, 29 individuals treated with CDs fabricated by simplified or conventional methods had their masticatory performance assessed 4 weeks after the prostheses’ adjustment and control, using the sieve method and almonds as a natural food test. Experimental variables related to age, gender, and previous use of complete dentures were collected from dental records. Panoramic digital radiographs were used to determine mandibular bone height according to the criteria described by the American College of Prosthodontists. Data on masticatory performance were assessed using t‐test for independent samples to make comparison between simplified and conventional methods, and a multiple linear regression analysis was performed to evaluate the influence of age, gender, previous experience with CDs, and mandibular bone height on masticatory performance using SPSS software with a significance level of 5%.

Results

There was no significant influence regarding the method for CD fabrication (p = 0.92), age (p = 0.36), mandibular bone height (p = 0.37), and previous experience with prostheses (p = 0.15) on masticatory performance of CD wearers. Female patients presented lower masticatory performance than male (p = 0.04) patients did.

Conclusions

Considering the limitations of this study, it was concluded that gender might be considered a risk factor for masticatory performance of CD wearers. Female patients demonstrated reduced masticatory performance in comparison to male patients.
Effect of Resin Cement Brand on the Color of Zirconia‐Based Restorations
Authors: Tabatabaian Farhad , Bakhshaei Delaram , Namdari Mahshid
Published: July 2018

Purpose

The purpose of this in vitro study was to evaluate the effect of resin cement brand on the color of zirconia‐based restorations.

Materials and Methods

Ninety A2 shade veneered zirconia disc specimens (0.5 mm zirconia thickness, 1 mm veneer thickness, 10 mm diameter) and 90 A3.5 shade composite resin background specimens (10 mm height, 10 mm diameter) with a superficial cement space (0.1 mm depth, 8 mm diameter) were fabricated. The zirconia specimens were cemented to the background specimens using universal resin cements: RelyX Unicem 2 (RU), PANAVIA SA Cement Plus (PS), and NX3 Nexus (NN). CIELab values were measured with a spectrophotometer before and after cementation. ∆E values were calculated to determine the color differences between before and after cementation of specimens (∆E1), and between the A2 VITA classical shade tab and specimens before cementation (∆E2) and after cementation (∆E3). The ΔE values were compared with an acceptability threshold (ΔE = 3.7) to evaluate color changes/matches. Welch, 1‐way ANOVA, Games‐Howell, Tukey HSD, and 1‐sample t test were used to analyze data (p < 0.05).

Results

Mean ΔE1 values were 0.6 ± 0.3 for RU, 0.8 ± 0.4 for PS, and 0.6 ± 0.2 for NN. Resin cement brand significantly affected the ΔE1 (p = 0.029) and the ΔE3 (p < 0.001). Mean ΔE3 values were 3.6 ± 0.3 for RU, 3.5 ± 0.3 for PS, and 3.9 ± 0.3 for NN. RU (p = 0.960) and PS (p = 0.999) showed a color match, but NN did not (p < 0.001).

Conclusions

The resin cement brand affected the color match of zirconia‐based restorations. Although the tested cements created minor color changes, RU and PS were better than NN for color match. The use of resin cements with the corresponding shade to the target shade is indicated.
Evaluation of age‐dependent changes of myocardial velocity using pulsed wave and colour tissue Doppler imaging in adult warmblood horses
Authors: Gehlen Heidrun , Bildheim Lisa‐Marie
Published: July 2018

Our aim was to evaluate the influence of the ageing process on the myocardium using pulsed wave tissue Doppler (PW‐TDI) and colour tissue Doppler imaging (cTDI) to measure myocardial velocities at three different myocardial regions (right ventricular free wall: RVFW, interventricular septum: IVS, left ventricular free wall: LVFW). A total of 60 healthy warmblood horses, aged from 3 to 30 years, were examined. The horses were divided into five age groups (group 1: 3–8 years,n = 14; group 2: 9–13 years,n = 9; group 3: 14–18 years,n = 10; group 4: 19–23 years,n = 14; group 5: 24–30 years,n = 10). The results showed that age has a significant influence on the radial myocardial velocity of horses in different myocardial regions. This influence was detectable by both echocardiographic techniques, although PW‐TDI measurements showed a higher reproducibility due to lower intraindividual variation coefficients. Systolic contraction velocity (p ≤ 0.01) and early diastolic relaxation velocity (p ≤ 0.001) in the LVFW decreased significantly with ageing, while late diastolic contraction velocity increased (0.001 < p ≤ 0.01). Early and late diastolic contraction velocities at the IVS increased significantly with ageing (p ≤ 0.001). Systolic and late‐diastolic contraction velocities at the RVFW increased significantly with ageing (p ≤ 0.001). The results indicated a decrease in left ventricular contraction ability and reduced myocardial relaxation and altered diastolic function in the right ventricle with increasing age. These functional changes may be signs of age‐related structural myocardial changes or cardiac remodelling, such as increased myocardial stiffness. Thus, an assessment of the radial myocardial velocities of a horse's heart with TDI should always consider physiological age‐related changes in contractility. Comparing the two examination techniques (PW‐TDI and cTDI) we used in our study, we found that both methods showed comparable age‐related alterations. Nevertheless, differences in absolute values were found with a tendency of higher values using PW‐TDI in comparison to cTDI.
Pharmacokinetics of intravenous, subcutaneous, and topical administration of lidocaine hydrochloride and metabolites 3‐hydroxylidocaine, monoethylglycinexylidide, and 4‐hydroxylidocaine in horse
Authors: Soma Lawrence R. , You Youwen , Robinson Mary A. , Boston Raymond C.
Published: July 2018

Abstact

Intravenous (iv), subcutaneous (sq), and topical (tp) lidocaine was administered to six horses in a cross‐over, randomized design study. Samples were collected for up to 72 hr. Compartmental models were used to investigate the pharmacokinetics of (LD) and its metabolites 3‐hydroxylidocaine (3‐OH), 4‐hydroxylidocaine (4‐OH), and monoethylglycinexylidide (MEGX). Metabolites 3‐OH and 4‐OH were present in conjugated forms, whereas LD and metabolite MEXG were present primarily in the un‐conjugated form. Plasma concentrations of LD after iv administration (100 mg) were described by three‐compartment model with an additional three compartments to describe the elimination of metabolites. Median (range) elimination micro‐constants (Ke) for LD, 3‐OH, 4‐OH, and MEXG were 4.12 (2.62–6.23), 1.25 (1.10–2.15), 1.79 (1.22–2.39), and 1.69 (1.03–1.99)/hr, respectively. Median (range) values of alpha (t½α), beta (t½β), and gamma (t½γ) half‐lives were 0.08 (0.07–0.13), 0.57 (0.15–1.25), and 4.11 (0.52–7.36) hr. Plasma concentrations of LD after sq (200 mg) administration were described by absorption and two‐compartment elimination model. The median (range) of the LD absorption half‐life (t½ab) was 0.47 (0.29–0.61) hr. TheKefor LD, 3‐OH, 4‐OH, and MEXG was 3.91 (1.48–9.25), 1.00 (0.78–1.08), 1.76 (0.96–2.11), and 1.13 (0.69–1.33)/hr. The median (range) oft½αandt½βwas 0.15 (0.06–0.27) and 3.04 (2.53–6.39) hr. Plasma concentrations of LD after tp (400 mg) application were described by one‐compartment model with at½abof 8.49 (5.16–11.80) hr. TheKefor LD, 3‐OH, and MEXG was 0.24 (0.10–0.81), 0.41 (0.08–0.93), and 0.38 (0.26–1.14)/hr.
Dissecting the role of a large chromosomal inversion in life history divergence throughout the Mimulus guttatus species complex
Authors: Coughlan Jennifer M. , Willis John H.
Published: July 2018

Chromosomal inversions can play an important role in adaptation, but the mechanism of their action in many natural populations remains unclear. An inversion could suppress recombination between locally beneficial alleles, thereby preventing maladaptive reshuffling with less‐fit, migrant alleles. The recombination suppression hypothesis has gained much theoretical support but empirical tests are lacking. Here, we evaluated the evolutionary history and phenotypic effects of a chromosomal inversion which differentiates annual and perennial forms of Mimulus guttatus. We found that perennials likely possess the derived orientation of the inversion. In addition, this perennial orientation occurs in a second perennial species, M. decorus, where it is strongly associated with life history differences between co‐occurring M. decorus and annual M. guttatus. One prediction of the recombination suppression hypothesis is that loci contributing to local adaptation will predate the inversion. To test whether the loci influencing perenniality pre‐date this inversion, we mapped QTLs for life history traits that differ between annual M. guttatus and a more distantly related, collinear perennial species, M. tilingii. Consistent with the recombination suppression hypothesis, we found that this region is associated with life history in the absence of the inversion, and this association can be broken into at least two QTLs. However, the absolute phenotypic effect of the LG8 inversion region on life history is weaker in M. tilingii than in perennials which possess the inversion. Thus, while we find support for the recombination suppression hypothesis, the contribution of this inversion to life history divergence in this group is likely complex.
Modelling the distribution of the vector Aedes aegypti in a central Argentine city
Authors: Estallo E. L. , Sangermano F. , Grech M. , Ludueña‐Almeida F. , Frías‐Cespedes M. , Ainete M. , Almirón W. , Livdahl T.
Published: July 2018

Aedes aegypti (Diptera: Culicidae) is an urban mosquito involved in the transmission of numerous viruses, including dengue, chikungunya and Zika. In Argentina, Ae. aegypti is the main vector of dengue virus and has been involved in several outbreaks in regions ranging from northern to central Argentina since 2009. In order to evaluate areas of potential vector‐borne disease transmission in the city of Córdoba, Argentina, the present study aimed to identify the environmental, socioeconomic and demographic factors driving the distribution of Ae. aegypti larvae through spatial analysis in the form of species distribution models (SDMs). These models elucidate relationships between known occurrences of a species and environmental data in order to identify areas with suitable habitats for that species and the consequent risk for disease transmission. The maximum entropy species distribution model was able to fit the training data well, with an average area under the receiver operating characteristic curve (AUC) of > 0.8, and produced models with fair extrapolation capacity (average test AUC: > 0.75). Human population density, distance to vegetation and water channels were the main variables predictive of the vector suitability of an area. The results of this work will be used to target surveillance and prevention measures, as well as in mosquito management.
Circadian rhythms and influencing factors of xerostomia among Parkinson’s disease patients
Authors: Barbe Anna Greta , Ludwar Lena , Scharfenberg Isabel , Hellmich Martin , Dano Richard , Barbe Michael Thomas , Noack Michael Johannes
Published: July 2018

Objectives

Parkinson's disease (PD) patients suffer from xerostomia, but limited information exists regarding associations with dysphagia, drooling, daily habits, PD characteristics, or possible circadian rhythms.

Subjects and methods

A questionnaire was administered, including (a) clinical characteristics (comorbidities, prescribed medications, levodopa equivalent daily dose [LEDD], disease duration); (b) self‐assessment of dysphagia, xerostomia, drooling (10‐cm visual analogue scale [VAS]); (c) 24‐hr diary of motor impairment, dyskinesia, xerostomia, dysphagia, drooling, daily habits.

Results

Of 75 PD patients who completed the study, 67% reported dysphagia (mean ± standard deviation VAS 4 ± 2), 76% drooling (5 ± 2), 77% xerostomia (5 ± 2). Xerostomia was associated with comorbidities (p = 0.021) and smoking (p = 0.010) and affected by tremor (p = 0.003), dyskinesia (p = 0.010), dysphagia (p < 0.001), food intake (p = 0.005), sleep (p = 0.011), age (p = 0.018), medication intake (p = 0.063), LEDD (p = 0.052), daytime (p = 0.075), disease duration (p = 0.004). Xerostomia peaked at 9 a.m. and 9 p.m.

Conclusions

PD patients suffer from xerostomia, dysphagia, and drooling. Subjective dysphagia is associated with drooling and xerostomia, but drooling prevalence or intensity does not influence xerostomia symptoms. Tremor, dyskinesia, and disease duration, which characterise PD, affect xerostomia. Additionally, food intake, sleep, age, LEDD, and daytime (peaks at 9 a.m. and 9 p.m.) increase xerostomia occurrence. This knowledge may improve dentists’ advice to patients and aid development of patient‐centred, symptom‐relieving products.
Effect of silencing a boule homologue on the survival and reproduction of Asian citrus psyllid Diaphorina citri
Authors: Yu Xiudao , Killiny Nabil
Published: July 2018

The fertility gene boule is conserved in most organisms and deletion of boule is found to block meiosis during spermatogenesis, which contributes to male infertility. The biological role of boule in Asian citrus psyllid Diaphorina citri, currently the most serious citrus pest and the vector of huanglongbing (HLB) pathogen, remains poorly understood. In the present study, a boule homologue in Diaphorina citri (DcBol) is identified and the potential application of DcBol for RNA interference (RNAi) based control of D. citri is evaluated. DcBol is constitutively expressed at gonadal and somatic tissues in both sexes. DsDcBol appears to be refractory to the salivary proteins of D. citri and no degradation is discovered over a 3‐day feeding period. DsRNA‐mediated RNAi of DcBol is achieved via artificial feeding, with DsDcBol at 400 ng μL−1 being sufficient to knockdown endogenous DcBol expression. A further bioassay reveals that knockdown of DcBol causes higher mortality of adult D. citri. In comparison with the control, the number of eggs and offspring nymphs generated by RNAi males is not reduced significantly. The results of the present study indicate that DcBol may play a limited role in male fertility.
The role of phenotypic plasticity and pollination environment in the cleistogamous, mixed mating breeding system of Triodanis perfoliata
Authors: Ansaldi B. H. , Weber J. J. , Franks S. J.
Published: July 2018

The role of variable pollination environments in maintaining mixed mating systems is an active area of research. Dimorphic cleistogamy, in which a plant reproduces by both open, facultative outcrossing chasmogamous (CH) flowers and closed, cleistogamous (CL) flowers presents an excellent opportunity to study mixed mating. For example, plastic responses in allocation to an optimal floral type could serve as an adaptive strategy that maintains mixed mating under variable pollination environments.

We tested for pollen limitation and plastic responses in allocation to different floral types under manipulated pollination conditions in the dimorphic cleistogamous, mixed mating annual, Triodanis perfoliata. Using a field population, we quantified pollen limitation, auto‐fertility and plastic responses in the breeding system by measuring allocation to flower number and seed set of floral types.

We found no evidence for pollen limitation for CH flowers, and CH flowers had low efficacy of autonomous selfing. Importantly, we found that T. perfoliata alters floral number following changes in pollination conditions, with pollen‐supplemented plants having lower relative CH flower number than non‐supplemented plants.

Breeding system plasticity may allow for benefits from outcrossing through CH flowers, but also increased overall fitness through relatively cheap CL reproduction. After CH flowers receive pollen, subsequent production of CH flowers was reduced, which may be due to resource limitation. Our findings did not support a theoretical model predicting increased CH flowers with high pollination levels. These results increase our understanding of the role of pollination services and resource allocation in the maintenance of mixed mating systems, which also warrants further investigation.
The Long-Run Effect of Childhood Poverty and The Mediating Role of Education
Authors: Bellani Luna , Bia Michela
Published: July 2018

The paper examines the role of education as a causal channel through which growing up poor affects the economic outcomes in adulthood in the European Union. We apply a potential outcomes approach to quantify those effects and we provide a sensitivity analysis on possible unobserved confounders, such as child ability. Our estimates indicate that being poor in childhood significantly decreases the level of income in adulthood and increases the average probability of being poor. Moreover, our results reveal a significant role of education in this intergenerational transmission. These results are particularly relevant for Mediterranean and central and eastern European countries.
Detecting Heteroscedasticity in Non-Parametric Regression Using Weighted Empirical Processes
Authors: Chown Justin , Müller Ursula U.
Published: July 2018

Heteroscedastic errors can lead to inaccurate statistical conclusions if they are not properly handled. We introduce a test for heteroscedasticity for the non-parametric regression model with multiple covariates. It is based on a suitable residual-based empirical distribution function. The residuals are constructed by using local polynomial smoothing. Our test statistic involves a ‘detection function’ that can verify heteroscedasticity by exploiting just the independence–dependence structure between the detection function and model errors, i.e. we do not require a specific model of the variance function. The procedure is asymptotically distribution free: inferences made from it do not depend on unknown parameters. It is consistent at the parametric (root n) rate of convergence. Our results are extended to the case of missing responses and illustrated with simulations.
False Discovery Rate Control for High Dimensional Networks of Quantile Associations Conditioning on Covariates
Authors: Xie Jichun , Li Ruosha
Published: July 2018

Motivated by gene coexpression pattern analysis, we propose a novel sample quantile contingency (SQUAC) statistic to infer quantile associations conditioning on covariates. It features enhanced flexibility in handling variables with both arbitrary distributions and complex association patterns conditioning on covariates. We first derive its asymptotic null distribution, and then develop a multiple-testing procedure based on the SQUAC statistic to test simultaneously the independence between one pair of variables conditioning on covariates for all p(p − 1)/2 pairs. Here, p is the length of the outcomes and could exceed the sample size. The testing procedure does not require resampling or perturbation and thus is computationally efficient. We prove by theory and numerical experiments that this testing method asymptotically controls the false discovery rate. It outperforms all alternative methods when the complex association patterns exist. Applied to a gastric cancer data set, this testing method successfully inferred the gene coexpression networks of early and late stage patients. It identified more changes in the networks which are associated with cancer survivals. We extend our method to the case that both the length of the outcomes and the length of covariates exceed the sample size, and show that the asymptotic theory still holds.
The D‐vitamin metabolite 1,25(OH)2D in serum is associated with disease activity and Anti‐Citrullinated Protein Antibodies in active and treatment naïve, early Rheumatoid Arthritis Patients
Authors: Herly Mette , Stengaard‐Pedersen Kristian , Vestergaard Peter , Østergaard Mikkel , Junker Peter , Hetland Merete L. , Hørslev‐Petersen Kim , Ellingsen Torkell
Published: July 2018

Rationale

Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis (RA). Most studies investigate only 25OHD and not the physiologically active vitamin D metabolite, 1,25(OH)2D.

Objective

To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25OHD2, 25OHD3 and 1,25(OH)2D) was measured by isotope dilution mass spectrometry and radio‐immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS28‐CRP, HAQ, VAS‐scores, CRP, erosive status (Total Sharp Score; TSS), ACPA and IgM‐RF‐status. Associations were evaluated using Spearman's and Wilcoxon rank‐sum tests. The study was registered in clinical trials; trial registration number: NCT00209859.

Findings

Statistically significant inverse associations were found between the active metabolite 1,25(OH)2D and DAS28‐CRP (P = 0.004, rho = −0.23), HAQ (P = 0.005, rho = −0.22), CRP (P = 0.001, rho = −0.25), VASpatient‐pain (P = 0.008, rho = −0.21), and a positive association was found to ACPA‐status (P = 0.04).

Conclusion

The vitamin D metabolite 1,25(OH)2D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA. The results indicate that in RA, both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect—or might be affected by the level of vitamin 1,25(OH)2D.
Analysis of Serbia UEFA Futsal Euro 2016 Competitions in Terms of Some Variables
Authors: Göral Kemal
Published: July 2018

The purpose of this study is to analyze the Serbia UEFA Futsal Euro 2016 competitions in terms of some variables. Range of goals scored by winner and defeated teams in form of 5 minute periods, shots on goal, corner, contributing to the score by starting 5 and substitutes, fouls, yellow-red cards, the range of goals according to shot techniques and goal zones were examined. While a total of 129 goals were scored with an average of 6.45 goals per game, with 25 goals (19.38%) most goals was scored between 36 and 40 minutes. 41.1% of goals were scored in penalty area, 58.9% of goals were scored from outside penalty area. While the rate of shots on goal in winner teams was 55.6%, this rate in defeated teams was 44.4%. In winner teams the players started in first 5 scored 50 goals (56.8%) and players joined from bench scored 38 goals (43.2%) and in defeated teams the first 5 scored 21 goals (60%) and the players joined from bench scored only 14 goals (40%). Winner teams while playing with flying keeper has scored 1 goal (16.7%) and conceded no goal; also, the defeated teams have scored 5 goals (83.3%) and conceded 13 goals when flying keeper in game. Substitutions in winner teams scored 133 goals, in defeated teams only 31 goals were scored by substitutions. As a result; accurate shots on goal, scoring in between 36-40th minutes, starting in first 5 and also joining from bench are accepted as an important factor to win a match, but despite providing an advantage of attacking with more player, the flying keeper tactic is not considered an effective element of winning the game according to the analysis of the data.
The Examination of Some Physical and Biomotor Parameters During the European Championship Preparation Camp of Turkey National Junior Women Boxing Team
Authors: Zileli Raif , Söyler Mehmet
Published: July 2018

The aim of this study is to examination of some physical and biomotor parameters of Turkey National Junior Women Boxing Team during six-week training camp before European Championship.27 boxers from Turkey National Junior Women Boxing Team participated in the research. The age of the boxers was x̅=15.85±0.45 years, the height of boxers was x̅=163.00±6.08cm and the body weight of boxers was x̅=63.78±14.30 kg. Boxers participating in the study were given a 6-week training program prepared and scheduled by Turkey Boxing Federation. Some physical and biomotorical parameters (body weight, BMI, body fat percentage, 10 meters speed, 30 meters speed, vertical jump, anaerobic power) of all boxers were measured at the beginning and at the end of the camp. Statistical processes of all data were analysed by SPSS 17.0 statistical package program. Normal distribution analyses were performed with the Shapiro-Wilk Test. Pre-test and post-test comparison of Body Mass Index and body weight values were analyzed by using the Wilcoxon Test and, pre-test and post-test comparison of body fat percentages, 10 m. speed, 30 m. speed, vertical jump and anaerobic power values were analyzed by using the Paired T test statistic. Significance value was taken as p <0.05.Changes in body weight values before and after camping were x̅=63.78±14.35 kg – x̅=61.25±14.31 kg, in BMI values x̅=23.09±5.44 kg/m2 – x̅=21.86±4.45 kg/m2, in body fat percentages x̅=26.91±9.50 – x̅=25.61±9.29, in 10 m speed values x̅=3.03±0.25 – x̅=2.93±0.23 sec, in 30 m speed values x̅=6.44±0.36 – x̅=6.25±0.34 sec, in vertical jump values x̅=0.21±0.09 to x̅=0.31±0.07 m and in anaerobic power x̅=63.71±20.13 – x̅=74.47±15.48 kgm/s, significant changes were seen statistically (p <0.05).As a result we suggest that the having a well-designed training camp can make a positive contribution on physical and biomotor parameters of national junior women boxers before an important tournament.