bluuebunny/crossref_metadata_2025 huggingface dataset:
Exposure to antazoline‐naphazoline eye drops during pregnancy and the risk of congenital malformations: a Danish nationwide cohort study
Authors: Thomseth Vilde , Cejvanovic Vanja , Jimenez‐Solem Espen , Poulsen Henrik E. , Utheim Tor Paaske , Andersen Jon T.
Published: November 2018

Purpose

To investigate whether exposure to antazoline‐naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans.

Methods

All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline‐naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non‐exposed offspring.

Results

We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline‐naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First‐trimester exposure to antazoline‐naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71–1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05).

Conclusion

Exposure to antazoline‐naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.
Support for National Flag‐Displays in Times of Change: A Question of National Identification?
Authors: Berndsen Mariëtte , Gausel Nicolay
Published: November 2018

Flag‐displays can be used within national groups to communicate majority supremacy over ethnic minorities. In two studies set in an Australian context (N = 88 and N = 102), we explain how mode of national identification (glorifying identifiers versus attached identifiers) differently predicts support for multicultural values and national flag‐displays. In line with the hypotheses, we found that attached identifiers were more supportive of multicultural values and national flag‐displays by ethnic minorities than glorifying identifiers. In contrast, glorifying identifiers supported flag‐displays by the majority more than did the attached identifiers. Study 2 demonstrates that glorifying identifiers’ use of the national flag is explicitly meant to exclude other groups. As expected, support for multicultural values and endorsement of the flag as an exclusion tool helped to explain the relationship between identification and flag‐displays. As such, results revealed the attitudes behind a novel form of prejudice that is currently on the rise.
Nightmares and hallucinations with aprepitant and opium powder: a suspected drug–drug interaction
Authors: Narjoux Grégoire , Clarenne Justine , Azzouz Brahim , Zeller Pauline‐Saraï , Slimano Florian , Bouché Olivier
Published: November 2018

Polypharmacy of elderly oncology patients and fragmented medication management are well‐known risk factors for drug–drug interactions (DDIs). These interactions can occur among antineoplastic, ongoing chronic treatment(s) and chemotherapy‐associated treatments, like antiemetics. Clinically relevant interactions based on enzyme‐ or transporter‐inhibition phenomena of active drugs can increase the frequency of their DDIs. We describe a strongly suspected elderly cancer patient's DDI between aprepitant and opium powder in the context of an irinotecan‐based regimen manifested by nightmares and visual hallucinations. We discuss this DDI's hypothetical pharmacological mechanisms and management.
Pharmacokinetics and pharmacodynamics of three dosages of oestriol after continuous vaginal ring administration for 21 days in healthy, postmenopausal women
Authors: Oliveira Filho Raimundo Vieira de , Antunes Natalícia de Jesus , Ilha Jaime de Oliveira , Moreno Ronilson Agnaldo , Wedemeyer Ralph‐Steven , Warnke André , De Nucci Gilberto
Published: November 2018

Aims

Evaluation of the oestriol pharmacokinetics, pharmacodynamics and safety in healthy, postmenopausal women under treatment with a vaginal ring with continuous delivery rates of 0.125 (Test 1), 0.250 (Test 2) or 0.500 mg day–1 (Test 3) for 21 days.

Methods

Thirty‐one subjects received a single application of Test 1, 2 or 3. The oestriol plasma concentration was determined by liquid chromatography coupled tandem mass spectrometry. Follicle‐stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone‐binding globulin serum concentrations, and maturation value (MV) and vaginal pH were assessed to describe the pharmacodynamics. Adverse events, local tolerability and endometrial thickness were evaluated to determine safety.

Results

The 90% confidence interval of the coefficient/slope β was 0.5997–1.174% for area under the curve of plasma concentration (AUC) up to the last measurement, 0.5838–1.115% for AUC extrapolated to infinity and 0.2408–0.943% for maximum plasma concentration. Dose proportionality could not be rejected for AUC, but a deviation from proportionality was statistically significant for maximum plasma concentration. The FSH and LH curves showed a decrease that was more pronounced with higher delivery rates; however, sex hormone‐binding globulin did not present this behaviour. A treatment effect on MV and vaginal pH was comparable for all formulations. All products showed increase in MV (70–80%) and the distribution of parabasal, intermediate and superficial cells showed a shift towards superficial cells. The vaginal pH values markedly decreased under treatment. The effect on endometrial thickness was not dose‐dependent.

Conclusion

All formulations released sufficient oestriol to trigger the maximum local effect. However, there was no difference between formulations regarding surrogate parameters for clinical efficacy. A dose‐dependency; however, was clearly demonstrated for FSH and LH. The product was well tolerated and safe.
Even if the fetus is not a person, abortion is immoral: The impairment argument
Authors: Hendricks Perry
Published: November 2018

Much of the debate about the ethics of abortion has centered on whether the fetus is a person. In an attempt to sidestep this complex issue, I argue that, even if the fetus is not a person, abortion is immoral. To arrive at this conclusion, I argue that giving a fetus fetal alcohol syndrome is immoral, and that if this is so, then killing the fetus is immoral. Roughly, this is because killing the fetus impairs it more than giving it fetal alcohol syndrome. Since abortion (in most cases) amounts to killing the fetus, this means that abortion (in most cases) is immoral. I defend the premises of this argument against a plethora of objections, concluding that they either do not work, or commit their proponent to a controversial position.
Causal parenthood and the ethics of gamete donation
Authors: Hanna Jason
Published: November 2018

According to the causal theory of parenthood, people incur parental obligations by causing children to exist. Proponents of the causal theory often argue that gamete donors have special obligations to their genetic offspring. In response, many defenders of current gamete donation practices would reject the causal theory. In particular, they may invoke the ‘too many parents problem’: many people who causally contribute to the existence of children – for instance, fertility doctors – do not thereby incur parental obligations. This article argues that the conclusions commonly drawn by causal theorists, and by their critics, are premature. Causal theorists have a promising response to the too many parents problem. This response, however, defuses the moral concern that many causal theorists have raised about gamete donation. A similar point, it is argued, applies to Rivka Weinberg's ‘Hazmat Theory’.
The Identity Objection to the future‐like‐ours argument
Authors: Brill Skott
Published: November 2018

Some critics of Don Marquis's ‘future‐like‐ours’ anti‐abortion argument launch what has been called the Identity Objection. The upshot of this objection is that under a psychological theory of personal identity, a non‐sentient fetus lacks precisely what Marquis believes gives it a right to life – a future like ours. However, Eric Vogelstein, in a recent article, has argued that under this theory of personal identity a non‐sentient fetus, in fact, has a future like ours, which he believes dissolves the Identity Objection. But Vogelstein is mistaken. Even if he is correct that there is a sense in which a non‐sentient fetus has a future of value under a psychological theory of personal identity, the sense in which it has one is importantly different from the sense in which we have one, meaning that, under such a theory, a non‐sentient fetus does not have a future like ours.
The effects of social exclusion on processing of social information – A cognitive psychology perspective
Authors: Syrjämäki Aleksi H. , Hietanen Jari K.
Published: November 2018

In this article, we review the research investigating the effects of social exclusion on processing of social information. We look into this topic from the point of view of cognitive psychology aiming to provide a systematic description of the effects of exclusion on workings of different cognitive mechanisms involved in social information processing. We focus on four lines of inquiry. First, we present the research on the effects of exclusion on memory for social information. Second, we review studies, which have investigated how exclusion changes the way people view and evaluate their social environment. Third, we look into the research which has investigated whether exclusion modulates early social information processing at the perceptual level. Finally, we discuss the research on the effects of exclusion on attentional processes. Importantly, we also present gaps in our understanding on these issues and provide suggestions as to how future research could provide a more detailed view on how exclusion modulates social information processing.
When pharmacology meets the microbiome: new targets for therapeutics?
Authors: Hyland Niall P , Cryan John F
Published: November 2018

Linked Articles

This article is part of a themed section on When Pharmacology Meets the Microbiome: New Targets for Therapeutics? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.24/issuetoc
Maintaining accountability between levels of governance in Indigenous economic development: Examples from British Columbia, Canada
Authors: Hotte Ngaio , Nelson Harry , Hawkins Tim , Wyatt Stephen , Kozak Robert
Published: November 2018

Many Indigenous communities in Canada have established economic development corporations (EDCs) to support economic development that meets community goals. Indigenous EDCs, like social enterprises, typically prioritize multiple socio‐economic goals and may be used to limit political influence on business operations; however, complete separation can be detrimental to success. This article explores formal mechanisms used by Indigenous EDCs to maintain accountability between levels of governance and ensure Indigenous community‐owned businesses remain focused on community objectives. A literature review, interviews and document analysis were used to identify formal mechanisms to maintain accountability in the context of Indigenous community‐owned forestry businesses in British Columbia, Canada.
Characterization and regulation of MT1‐MMP cell surface‐associated activity
Authors: Pahwa Sonia , Bhowmick Manishabrata , Amar Sabrina , Cao Jian , Strongin Alex Y. , Fridman Rafael , Weiss Stephen J. , Fields Gregg B.
Published: November 2018

Quantitative assessment of MT1‐MMP cell surface‐associated proteolytic activity remains undefined. Presently, MT1‐MMP was stably expressed and a cell‐based FRET assay developed to quantify activity toward synthetic collagen‐model triple‐helices. To estimate the importance of cell surface localization and specific structural domains on MT1‐MMP proteolysis, activity measurements were performed using a series of membrane‐anchored MT1‐MMP mutants and compared directly with those of soluble MT1‐MMP. MT1‐MMP activity (kcat/KM) on the cell surface was 4.8‐fold lower compared with soluble MT1‐MMP, with the effect largely manifested in kcat. Deletion of the MT1‐MMP cytoplasmic tail enhanced cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin‐like domain negatively impacted KM and increased kcat. Overall, cell surface localization of MT1‐MMP restricts substrate binding and protein‐coupled motions (based on changes in both kcat and KM) for catalysis. Comparison of soluble and cell surface‐bound MT2‐MMP revealed 12.9‐fold lower activity on the cell surface. The cell‐based assay was utilized for small molecule and triple‐helical transition state analog MMP inhibitors, which were found to function similarly in solution and at the cell surface. These studies provide the first quantitative assessments of MT1‐MMP activity and inhibition in the native cellular environment of the enzyme.
UNEXPECTED DIVERSITY OF AUSTRALIAN TOBACCO SPECIES (NICOTIANA SECTION SUAVEOLENTES, SOLANACEAE)
Authors: Chase Mark W. , Christenhusz Maarten J. M. , Conran John G. , Dodsworth Steven , Medeiros de Assis Felipe Nollet , Felix Leonardo P. , Fay Michael F.
Published: November 2018

This special issue highlights some of the wonderful species of native Australian tobacco (Nicotiana sect. Suaveolentes). We here present twelve species of this genus, four of which are new to science. Many Nicotiana species have a high ornamental value, and we hope that particularly the rarer Australian species will find a way into horticulture to prevent them from becoming threatened. This would allow maintenance of ex‐situ populations, mitigating the effects of changing climate and introduction of invasive species. Tobaccos dispersed into the Australian outback around two million years ago and are now radiating there. It has been clear that they have interesting cytological evolution as well as morphological differences. They appear to have peculiar drought adaptations, which are needed for thin‐leaved herbs growing in some of the driest places on the planet.
884. NICOTIANA YANDINGA
Authors: Chase Mark W. , Conran John G. , Christenhusz Maarten J. M.
Published: November 2018

Nicotiana yandinga is newly described here and illustrated from plants collected in the Gawler Ranges in South Australia and cultivated at the Royal Botanic Gardens, Kew. Its discovery, ecology, cytology and cultivation are discussed.
885. NICOTIANA GASCOYNICA
Authors: Chase Mark W. , Christenhusz Maarten J. M.
Published: November 2018

Nicotiana gascoynica is newly described and illustrated from plants collected in the Gascoyne region of Western Australia and cultivated at the Royal Botanic Gardens, Kew. Its discovery, ecology, cytology and cultivation are discussed.
Smoking behaviours among heterosexual and sexual minority youth? Findings from 15 years of provincially representative data
Authors: Fish Jessica N. , Watson Ryan J. , Gahagan Jacqueline , Porta Carolyn M. , Beaulieu‐Prévost Dominic , Russell Stephen T.
Published: November 2018

Introduction and Aims

Sexual identity disparities in smoking behaviours are well established; however, there is limited research on whether these disparities have diminished as the social and political landscape has changed for lesbian, gay and bisexual people. Thus, we examined changes in prevalence and sexual identity disparities in three smoking behaviours among Canadian adolescents from 1998 to 2013.

Design and Methods

Data are from the provincially representative British Columbia Adolescent Health Survey (N = 99 373). Using sex‐stratified, age‐adjusted logistic regression models, we estimated: (i) trends in lifetime cigarette use, early onset, and past 30‐day use for heterosexual and three subgroups of sexual minority (i.e. mostly heterosexual, bisexual and gay/lesbian) youth; (ii) sexual identity disparities in these cigarette‐related behaviours within each survey year (1998, 2003, 2008, 2013); and (iii) whether the size of the disparity has changed from 1998 to 2013.

Results

Smoking has declined for all youth from 1998 to 2013, although less consistently for sexual minority youth. Within‐year disparity estimates indicated elevated prevalence of cigarette use for sexual minority compared to heterosexual youth, particularly among females. Trends in sexual identity and smoking behaviours indicated that the degree of differences between heterosexual and sexual minority youth have remained stable or, in some cases, widened. Heterosexual and sexual minority youth differences widened for early onset among sexual minority boys and lifetime and past 30‐day use for sexual minority girls.

Discussion and Conclusions

Efforts to prevent smoking behaviours among youth should continue. Tailored preventive strategies for sexual minority youth might help address existing disparities.
DREAM5: An open‐label, randomized, cross‐over study to evaluate the safety and efficacy of day and night closed‐loop control by comparing the MD‐Logic automated insulin delivery system to sensor augmented pump therapy in patients with type 1 diabetes at home
Authors: Biester Torben , Nir Judith , Remus Kerstin , Farfel Alon , Muller Ido , Biester Sarah , Atlas Eran , Dovc Klemen , Bratina Nataša , Kordonouri Olga , Battelino Tadej , Philip Moshe , Danne Thomas , Nimri Revital
Published: November 2018

Aims

Previous DREAM studies demonstrated the safety and efficacy of the CE marked MD‐Logic closed‐loop system (DreaMed GlucoSitter) in different settings for overnight glycaemic control. The present study aimed to evaluate the system for day and night use for 60 hours during the weekend at home compared to sensor‐augmented pump (SAP) therapy in participants with type 1 diabetes.

Methods

This was a prospective, multicentre, crossover, controlled study (clinicaltrials.gov NCT01238406). All participants were connected in randomized order for one weekend to SAP therapy or the MD‐Logic System. In the intervention arm only, the amount of carbohydrate was entered into the bolus calculator; the rest of insulin delivery was automated and wireless via a tablet computer. The primary endpoint was percentage of glucose values between 70 and 180 mg/dL.

Results

The ITT population comprised 48 (19 males, 29 females) adolescents and adults experienced in sensor use: (median, [IQR]): age, 16.1years [13.2‐18.5]; diabetes duration, 9.4 years [5.0‐12.7]; pump use, 5.4 years [3.1‐9.4]; HbA1c, 7.6% [7.0‐8.1]. A significant increase in the percentage of time within target range (70‐180 mg/dL) (66.6% vs 59.9%, P = 0.002) was observed with the closed‐loop system vs control weekends with unchanged percentage of time below 70 mg/dL (2.3% vs 1.5%, P = 0.369). Mean weekend glucose level per participant was significantly lower (153 [142‐175] vs 164 [150‐186] mg/dL, P = 0.003). No safety signals were observed.

Conclusions

The MD‐Logic system was safe and associated with better glycaemic control than SAP therapy for day and night use. The absence of remote monitoring did not lead to safety signals in adapting basal rates nor in administration of automated bolus corrections.
Is the longitudinal deformation of the left ventricle affected by vitamin D deficiency in nondiabetics? A 2D speckle‐tracking echocardiographic study
Authors: Omidi Fatemeh , Hosseinsabet Ali
Published: November 2018

Objectives

Vitamin D deficiency with its high global prevalence is associated with some pathological changes in the myocardium. The aim of our study was to assess the longitudinal deformation of the left ventricular (LV) myocardium in subjects with vitamin D deficiency.

Methods

This cross‐sectional study recruited 98 consecutive nondiabetic subjects (45 subjects with vitamin D deficiency and 53 subjects without vitamin D deficiency) without significant epicardial coronary artery stenosis. The longitudinal subendocardial deformation indices of the LV myocardium were evaluated with 2D speckle‐tracking echocardiography.

Results

The end‐systolic strain, the systolic strain rate, and the early and late diastolic strain rates were not statistically significantly different between the subjects with and without vitamin D deficiency.

Conclusions

The global longitudinal subendocardial deformations of the LV, including the systolic strain rate and the systolic and diastolic strain rates, as evaluated with 2D speckle‐tracking echocardiography were not statistically significantly correlated with the presence or absence of vitamin D deficiency.
Has carotid intima‐media thickness prognostic impact in patients with high cardiovascular risk? A long‐term cohort study
Authors: Timóteo Ana Teresa , Mota Carmo Miguel , Soares Cristina , Ferreira Rui Cruz
Published: November 2018

Background

Carotid intima‐media thickness (CIMT) is an established surrogate marker for cardiovascular events in patients with intermediate risk. In patients with high cardiovascular risk or established cardiovascular disease, the impact of CMIT measurement on risk stratification for future events is less clear. Our objective was to evaluate the impact of CIMT on the occurrence of cardiovascular events in a cohort of individuals with high cardiovascular risk, in long‐term follow‐up.

Methods

We analyzed 296 individuals, mean follow‐up of 6.9 ± 2.2 years. Individuals were divided into tertiles according to CIMT. Tertiles were compared in terms of baseline characteristics and outcomes during follow‐up—all‐cause mortality and composite outcome (mortality, acute coronary syndromes, coronary revascularization, stroke/transient ischemic attack, heart failure, or cardiovascular admission).

Results

Our population had a mean age of 65 ± 9 years at the beginning of the study, 55% males. Patients with higher CIMT showed a trend for higher cardiovascular mortality (P = 0.084) and for the composite outcome (P = 0.049). A CIMT ≥ 0.85 mm was also associated with higher rate of events; however, CIMT was not an independent predictor of outcome after adjustment for age and gender. CIMT assessment was useful in patients with hypertension, hyperlipidemia, and metabolic syndrome and in nondiabetic patients. For the composite outcome, it was also useful in females, smokers, and in patients without coronary artery disease.

Conclusions

Patients with higher CIMT have worst outcome, but this was mainly driven by age and gender. CIMT is useful as a prognostic marker in specific subsets of patients.
Trends in use of echocardiography in hospitalized patients with syncope
Authors: Satish Mohan , Walters Ryan W. , Alla Venkata Mahesh
Published: November 2018

Purpose

We sought to assess the trends in use, predictors of echocardiography, and its impact on in‐hospital mortality in patients admitted with syncope using a large national database.

Methods

Utilizing the Nationwide Inpatient Sample (NIS) database from 2001 to 2014, we identified adult patients (>18 years) with a primary discharge diagnosis of syncope and use of echocardiogram was ascertained.

Results

A total of 3 174 619 patients with a primary discharge diagnosis of syncope were identified, of which 184 167 (5.8%) underwent an echocardiogram. The rate of syncope hospitalization remained constant between 2001 and 2009 (1.1/1000 US population) but has since decreased steadily to about 0.5/1000 US population in 2014. After adjusting for patient and hospital characteristics, the rate of echocardiogram use increased significantly from 5.1% in 2001 to 6.8% in 2014 (2.7% relative increase per year [Ptrend = 0.024]). Predictors of use were cardiac disorders, hypertension, diabetes, peripheral vascular disease, and renal failure. After adjusting for baseline risk, use of echocardiography was not associated with in‐hospital mortality (OR = 0.827, P = 0.155), but was associated with a 14.6% increase in adjusted length of stay and a 22.6% increase in adjusted hospital cost compared to no echocardiography use (both P < 0.001).

Conclusions

The admission rates for syncope are decreasing and use of echocardiography in hospitalized patients with syncope is appropriately low. Given the lack of any favorable impact on mortality and the association with increased costs, there is a continued need to emphasize evidence‐based use of echocardiography in patients presenting with syncope.
Calcific metamorphosis of pulp after extrusive luxation
Authors: Queiroz Alfredo Franco , Hidalgo Mirian Marubayashi , Consolaro Alberto , Panzarini Sônia Regina , França Alline Batistussi , Pires Willian Ricardo , Poi Wilson Roberto
Published: November 2018

Background/Aim

The literature on the pathogenesis of extrusive dental luxation has been focused on periodontal tissue responses, with little attention given to the pulp. The aim of this study was to evaluate the response of dental pulp of teeth following extrusive luxation in a rat model.

Material and Methods

The maxillary right central incisors of 30 rats were extrusively luxated and repositioned after 5 minutes. The animals were euthanized after 7, 15, and 30 days to provide three groups: I, II, and III, respectively (n = 10). Histological sections were stained with H and E for histomorphometric analysis of the odontoblast layer, reparative dentin deposition, Hertwig's epithelial root sheath, pulp necrosis, and periapical inflammatory infiltrate.

Results

In most cases, new vascular formation occured in association with reparative dentin deposition on the root walls and within the pulp. In some cases, dentin deposition occupied the entire pulp space over time, with no other types of non‐odontogenic hard tissues being observed. Pulp necrosis with the presence of periapical inflammatory infiltrate was also observed in a few cases. No statistical differences were observed among the studied groups.

Conclusions

Following extrusive luxation, calcific metamorphosis of the pulp is very likely to occur.
Exploring the predictive performance of several temperature measurements on Neotropical dung beetle assemblages: Methodological implications
Authors: Lobo Jorge M. , Da Silva Pedro G. , Hensen Maristela C. , Amore Valentina , Hernández Malva I. M.
Published: November 2018

Basic characteristics of species assemblages are frequently related to temperature variables recorded at a coarse‐grained scale. In this study, 15 min instant‐measurements of environmental and soil temperatures were recorded during 1 year in six Atlantic Forest sites of southern Brazil, ranging from 250 to 1,630 m a.s.l. These measurements were used to examine the comparative explanatory capacity of several temperature variables in predicting species richness and total or specific variations of dung beetle abundance. The results suggest that temperature measurements obtained during the survey period have the highest explanatory capacity. Furthermore, average temperature values seem to have a relatively higher explanatory capacity than absolute minimum or maximum values reflecting extreme conditions. In general, there is no rule in selecting a temperature variable when the objective involves explaining the variation in species abundances. Both soil and air variables can have similar explanatory capacities. The present results should be considered when designing future ecological studies in Neotropical conditions.
The structure of Legionella effector protein LpnE provides insights into its interaction with Oculocerebrorenal syndrome of Lowe (OCRL) protein
Authors: Voth Kevin A. , Chung Ivy Yeuk Wah , van Straaten Karin , Li Lei , Boniecki Michal T. , Cygler Miroslaw
Published: November 2018

Legionella pneumophila is a freshwater bacterium that replicates in predatory amoeba and alveolar macrophage. The ability of L. pneumophila to thrive in eukaryotic host cells is conferred by the Legionella containing vacuole (LCV). Formation and intracellular trafficking of the LCV are governed by an arsenal of effector proteins, many of which are secreted by the Icm/Dot Type 4 Secretion System. One such effector, known as LpnE (L. pneumophila Entry), has been implicated in facilitating bacterial entry into host cells, LCV trafficking, and substrate translocation. LpnE belongs to a subfamily of tetratricopeptide repeat proteins known as Sel1‐like repeats (SLRs). All eight of the predicted SLRs in LpnE are required to promote host cell invasion. Herein, we report that LpnE(1‐375) localizes to cis‐Golgi in HEK293 cells via its signal peptide (aa 1–22). We further verify the interaction of LpnE(73‐375) and LpnE(22‐375) with Oculocerebrorenal syndrome of Lowe protein (OCRL) residues 10–208, restricting the known interacting residues for both proteins. To further characterize the SLR region of LpnE, we solved the crystal structure of LpnE(73‐375) to 1.75Å resolution. This construct comprises all SLRs, which are arranged in a superhelical fold. The α‐helices forming the inner concave surface of the LpnE superhelix suggest a potential protein–protein interaction interface.

Database

Coordinates and structure factors were deposited in the Protein Data Bank with the accession number 6DEH.
Impact of particle packing mix design method on fracture properties of natural and recycled aggregate concrete
Authors: Pradhan Subhasis , Kumar Shailendra , Barai Sudhirkumar V.
Published: November 2018

The fracture properties of four types of concrete prepared using natural coarse aggregate and recycled coarse aggregate and conventional and particle packing method (PPM) of mix design approaches are studied. The three‐point bending (TPB) test is performed using three different sizes of single edge notched beam. The fracture energy is calculated from the load‐CMOD curve obtained in the TPB test, and in this process the load‐CMOD curve is curtailed at 2% of the depth of the beam. Based on CTODc and w1 relationship, appropriate softening function is used to estimate the double‐K fracture parameters. The fracture energy and fracture toughness parameters of recycled aggregate concrete (RAC) is inferior to the natural aggregate concrete (NAC). The PPM mix design improves the fracture properties of concrete in comparison to the conventional mix design approach. The fracture properties of PPM mix designed RAC are comparable to that of NAC prepared using conventional method.
Social network analysis of sheep grazing different plant functional groups
Authors: Yiakoulaki Maria D. , Hasanagas Nikolaos D. , Michelaki Eleni , Tsiobani Eleni T. , Antoniou Ioannis E.
Published: November 2018

Social Network Analysis (SNA) is used for the first time to investigate the relations between plant functional groups and social structure of grazing sheep. The research was conducted on a grassland in Crete's island Lefka Ori, Greece during 2016. A flock of 20 sheep of Sfakion race was analysed as a network and the sheep as nodes. The focal sampling technique was applied during four experimental periods of four consecutive days × eight hours/day. The plant species selected by sheep during grazing were categorized into four functional groups (grasses, broad‐leaved forbs, shrubs and trees), and the proximity and conflict relations that were developed among the flock members were recorded. The tools of SNA were defined and interpreted in the sheep flock, and the Visone software is used to calculate the network variables of proximity and conflicts relations of nodes. Correlations between the plant functional groups and network variables were examined by Spearman's bivariate correlation test. Sheep collectivity was enhanced while grazing grasses and simultaneously, a tendency for hierarchization within the flock was identified. Similarly, the proximity of sheep increased during forbs’ grazing while their individualism was strengthened. When grazing shrubs, the proximity of sheep was only in part maintained while the grazing of trees seems as the most deconstructive forage option of sheep proximity relations. In general, the grazing of all plant functional groups decreases conflicts among sheep except that of trees, which was insignificant for developing such relations.
The cohesin complex in mammalian meiosis
Authors: Ishiguro Kei‐ichiro
Published: November 2018

Cohesin is an evolutionary conserved multi‐protein complex that plays a pivotal role in chromosome dynamics. It plays a role both in sister chromatid cohesion and in establishing higher order chromosome architecture, in somatic and germ cells. Notably, the cohesin complex in meiosis differs from that in mitosis. In mammalian meiosis, distinct types of cohesin complexes are produced by altering the combination of meiosis‐specific subunits. The meiosis‐specific subunits endow the cohesin complex with specific functions for numerous meiosis‐associated chromosomal events, such as chromosome axis formation, homologue association, meiotic recombination and centromeric cohesion for sister kinetochore geometry. This review mainly focuses on the cohesin complex in mammalian meiosis, pointing out the differences in its roles from those in mitosis. Further, common and divergent aspects of the meiosis‐specific cohesin complex between mammals and other organisms are discussed.
Squamous cell carcinoma of the nail unit: a retrospective review of 19 cases in Asia and comparative review of Western literature
Authors: Lee Tae‐Min , Jo Gwanghyun , Kim Minsoo , Lee Si‐Hyung , Cho Soo Ick , Jo Seong J. , Mun Je‐Ho
Published: November 2018

Background

Reports regarding squamous cell carcinoma of the nail unit (SCCnu) are rare in Asia.

Objectives

To investigate the features of SCCnu in the Asian population.

Method

We performed a retrospective review of patients diagnosed with SCCnu at our institution between 2012 and 2017.

Results

Nineteen cases were included. Thirteen patients were male (68.4%). The fingers were most frequently affected (73.7%). Mean delay to diagnosis was 62.4 months. Misdiagnosis rate was high (78.9%). Frequent clinical features were subungual tumor, subungual hyperkeratosis, nail dystrophy, ulcer, and nail loss. The majority of cases were invasive SCC in 15 cases (78.9%), while SCC in situ was found in four cases (21.1%). Local recurrence was detected in two cases (10.5%) following surgical resection. However, distant metastasis was not reported.

Conclusion

This study provides data of 19 SCCnu cases in Asia. Clinical characteristics of SCCnu in this study were similar to those of reports from Western countries. However, we found a higher frequency of more invasive cases and longer delay to diagnosis in our study; this advocates the need for greater attention on nail disorders among healthcare providers, particularly in Asia.
The use of electrochemotherapy in combination with immunotherapy in the treatment of metastatic melanoma: a focused review
Authors: Goggins Clare A. , Khachemoune Amor
Published: November 2018

Electrochemotherapy (ECT) is a treatment modality that combines low‐dose chemotherapy with electroporation, thereby enhancing cytotoxicity. ECT was first utilized in the treatment of metastatic head and neck cancer. Today it is used as a local treatment for the cutaneous and subcutaneous metastases of a variety of cancers, including melanoma. In addition, recent evidence indicates that ECT in combination with immunotherapy can lead to a systemic tumor response. This review aims to summarize the efficacy of ECT in the treatment of metastatic melanoma, with a specific focus on the combination of ECT with immunotherapy.
Male infertility in Sertoli cell‐only syndrome: An investigation of autosomal gene defects
Authors: Koc Gulsah , Ozdemir Abdullah A , Girgin Gozde , Akbal Cem , Kirac Deniz , Avcilar Tuba , Guney Ahmet I
Published: November 2018

Objectives

To detect autosomal genetic defects and to determine candidate genes in Sertoli cell‐only syndrome infertile men.

Methods

Single‐nucleotide polymorphism + comparative genomic hybridization microarray technology was carried out on 39 Sertoli cell‐only syndrome infertile patients in the present study. Array comparative genomic hybridization compares the patient's genome against a reference genome, and identifies uncover deletions, amplifications and loss of heterozygosity.

Results

A link between defective spermatogenesis genes and infertility was examined, and amplifications and deletions in several genes were detected, including homeobox gene; synaptonemal complex element protein 1; collagen, type I, alpha 1; imprinted maternally expressed transcript; and potassium voltage‐gated channel subfamily Q member 1.

Conclusions

The present data suggest that several genes can play an important role in spermatogenesis and progression of Sertoli cell‐only syndrome.
Characteristics and outcomes of patients with acute liver failure admitted to Australian and New Zealand intensive care units
Authors: Warrillow Stephen , Bailey Michael , Pilcher David , Kazemi Alex , McArthur Colin , Young Paul , Bellomo Rinaldo
Published: November 2018

Background

Knowledge about patients with acute liver failure (ALF) in Australia and New Zealand (ANZ) is lacking.

Aims

To evaluate whether the pattern of ALF would be similar to previous studies and whether, despite potentially low transplantation rates, mortality would be comparable.

Methods

We obtained data from the ANZ Intensive Care Society Adult Patient Database and the ANZ Liver Transplant Registry for 10 years commencing 2005 and analysed for patient outcomes.

Results

During the study period, 1 022 698 adults were admitted to intensive care units across ANZ, of which 723 had ALF. The estimated annual incidence of ALF over this period was 3.4/million people and increased over time (P = 0.001). ALF patients had high illness severity (Acute Physiology And Chronic Health Evaluation III 79.8 vs 50.1 in non‐ALF patients; P < 0.0001) and were more likely to be younger, female, pregnant and immunosuppressed. ALF was an independent predictor of mortality (odds ratio 1.5 (1.26–1.79); P < 0.0001). At less than 23%, the use of liver transplantation was low, but the mortality of 39% was similar to previous studies.

Conclusions

ALF is a rare but increasing diagnosis in ANZ intensive care units. Low transplantation rates in ANZ for ALF do not appear to be associated with higher mortality rates than reported in the literature.
Development of a parents’ short form survey of their children's oral health
Authors: Wang Yan , Hays Ron , Marcus Marvin , Maida Carl , Shen Jie , Xiong Di , Lee Steve , Spolsky Vladimir , Coulter Ian , Crall James , Liu Honghu
Published: November 2018

Background

Parents play an important role in their children's oral health behaviors, provide oral health access, initiate prevention, and coping strategies for health care.

Aim

This paper develops a short form (SF) to assist parents to evaluate their children's oral health status using Patient‐Reported Outcome Measurement Information System (PROMIS) framework that conceptualized health as physical, mental, and social components.

Design

Surveys of parents were conducted at dental clinics in Los Angeles County, together with an on‐site clinical examination by dentists to determine clinical outcomes, Children's Oral Health Status Index (COHSI), and referral recommendations (RRs). Graded response models in item response theory were used to create the SF. A toolkit including SF, demographic information, and algorithms was developed to predict the COHSI and RRs.

Results

The final SF questionnaire consists of eight items. The square root mean squared error for the prediction of COHSI is 7.6. The sensitivity and specificity of using SF to predict immediate treatment needs (binary RRs) are 85% and 31%.

Conclusions

The parent SF is an additional component of the oral health evaluation toolkit that can be used for oral health screening, surveillance program, policy planning, and research of school‐aged children and adolescents from guardian perspectives.
Biological Markers of Alcoholism With Respect to Genotypes of Low‐Km Aldehyde Dehydrogenase (ALDH2) in Japanese Subjects
Authors: Nomura Fumio , Itoga Sakae , Tamura Masaki , Harada Shoji , Lizuka Yoshiaki , Nakai Toshiaki
Published: November 2018

Background: Although the mutant low‐Km acetaldehyde dehydrogenase (ALDH2) allele (ALDH22) with reduced capacity to metabolize acetaldehyde offers biological protection against alcoholism and subsequent alcohol‐induced organ damage in many individuals, a significant proportion of individuals with heterozygote of the normal and mutant ALDH2 gene (ALDH21/22) consume excessive amounts of alcohol. Indeed, it has been postulated that habitual drinkers with ALDH21/22 may be at a higher risk for alcoholic liver disease than those with ALDH21/21. In this study, we determined how representative biological markers of alcoholism (γ‐glutamyltransferase [GGT], carbohydrate‐deficient transferrin [CDT], and the mean corpuscular volume of erythrocytes [MCV]) differ with respect to the ALDH2 genotypes in Japanese habitual drinkers.

Methods: We obtained genomic DNA samples from 227 Japanese men with various drinking habits. ALDH2 genotypes were determined by allele‐specific polymerase chain reaction. GGT, CDT, and MCV were determined and compared between ALDH21/21 and ALDH21/22 habitual drinkers who consumed more than 66 g of alcohol per day for more than 5 years. We measured CDT by anion‐exchange chromatography followed by turbidity immunoassay by using a commercially available assay kit (Axis %CDT TIA).

Results: CDT levels were comparable between the two groups. GGT activities were significantly greater in ALDH21/21 than in ALDH21/22 habitual drinkers (81 ± 85 vs. 53 ± 40 IU/liters, p < 0.02). MCV values, on the other hand, were significantly larger in ALDH21/22 than in ALDH21/21 subjects (98.2 ± 5.8 vs. 95.8 ± 4.2 fl, p = 0.02). When we used elevation of either CDT or GGT to detect habitual drinking in ALDH21/21 and 21/22 subjects, the sensitivities were 57% and 46%, respectively. CDT levels were similar between habitual drinkers with normal aspartate aminotransferase levels and those with elevated levels.

Conclusion: GGT and MCV, but not CDT, differ with respect to the ALDH2 genotypes in Japanese male habitual drinkers. ALDH2 genotypes should be considered when interpreting data on biological markers of alcoholism.
A Study of Colloidal Scintigraphy in Alcoholic Liver Diseases: Discordance from Asialo‐Scintigraphic Findings
Authors: Koreeda Chizu , Kawa Sang Kil Ha , Takasu Masahi , Satoh Masahiro , Takemoto Hiroto , Mizuno Takako , Sawada Satoshi , Inoue Kyouichi
Published: November 2018

Background: Our study was undertaken to check the discordance between findings from 99mTc‐Sn colloidal reticuloendothelial scintigraphy (RESS) and 99mTc‐GSA asialo‐scintigraphy (GSA, a technique for evaluation of liver parenchymal cell density and function) and to analyze the discordance in relation to functional disturbances. We compared data between patients with alcoholic liver diseases (ALD) and patients with viral liver diseases (VLD).

Methods: The subjects of this study were 40 patients with chronic liver disease (17 with ALD and 23 with VLD). We used the liver uptake ratio of the tracer of the Sn colloid (SnL15, %), the liver uptake rate (GSAL15, %), and the Rmax (an indicator of total liver receptors) as indices of liver scans.

Results: GSAL15 was sometimes nondiscordant from SnL15. The patients were divided into two groups: the nondiscordant group (26 cases where the balance/sum of the two variables was <25%) and the discordant group (14 cases where the balance/sum was >25%). SnL15 was 41.6 ± 16.2% in the nondiscordant group and 42.7 ± 16.3% in the discordant group (p = 0.80). GSAL15 was 34.3 ± 12.1% in the nondiscordant group and 21.5 ± 8.1% in the discordant group (p = 0.001). Rmax was 0.33 ± 0.17 in the nondiscordant group and 0.113 ± 0.008 in the discordant group (p = 0.002). Thus, the SnL15, as determined by RESS, did not differ significantly between the nondiscordant and discordant groups, whereas GSAL15 was significantly unfavorable in the discordant group as compared with the nondiscordant group. SnL15 as determined by RESS did not differ significantly between the ALD group (40.4 ± 18.7%) and the VLD group (43.5 ± 15.0%) (p = 0.59), whereas Rmax as determined by GSA was significantly improved in the ALD group (0.34 ± 0.20) compared with the VLD group (0.20 ± 0.4) (p = 0.02).

Conclusions: Liver cell function was lower in cases that showed discordance between liver cell function and reticuloendothelial function compared with cases without such discordance, although reticuloendothelial function did not differ between discordant and nondiscordant groups. Liver cell function was better in cases of ALD than in cases of VLD, whereas reticuloendothelial function did not differ between the ALD group and the VLD group.
Clinical Characteristics of Patients in Their 40s With HCV Antibody‐Positive Hepatocellular Carcinoma
Authors: Shimauchi Yoshihiro , Tanaka Masatoshi , Koga Kenshi , Itano Satoshi , Ishii Kunihide , Kumashiro Ryukichi , Sakisaka Shotaro , Sata Michio
Published: November 2018

Background: We investigated the clinical characteristics of hepatitis C virus (HCV) antibody‐positive hepatocellular carcinoma (HCC) patients who developed HCC at a relatively young age.

Methods: Clinical characteristics of patients in their 40s were investigated and were compared with those of patients 50 years and older. The subjects were 648 HCC patients, 469 men (72%) and 179 women (28%), who were treated at our hospital between 1991 and 1997.

Results: No patient was under 40 years of age. Eighteen patients (3%) were in their 40s, 137 patients (21%) were in their 50s, 338 patients (52%) were in their 60s, 143 patients (22%) were in their 70s, and 12 patients (2%) were in their 80s. Fifteen of the patients (83%) in their 40s were male. The proportion of men in their 40s was higher than that of all men. Eight of the 15 men in their 40s (53%) were heavy drinkers, and 2 (14%) were habitual drinkers. Three of the 15 men (20%) were HBV carriers, and these 3 HBV carriers were not drinkers. The proportion of heavy drinkers and HBV carriers was significantly higher among the patients in their 40s than in the 60 patients randomly sampled from the patients 50 years of age and older. The mean ages of male patients with HCC who were heavy drinkers, habitual drinkers, occasional drinkers, or nondrinkers were 52.3, 58.9, 62.0, and 61.7 years, respectively. HCC occurred significantly earlier in heavy drinkers than in the other 3 groups. We compared laboratory data of the patients in their 40s with data of all of the patients of 50 years and older. Serum total bilirubin, prothrombin time, and platelet counts were significantly worse in the patients in their 40s.

Conclusions: Logistic regression analysis revealed that heavy drinking and presence of HBV infection were independently related to HCV antibody‐positive HCC development at a younger age.