bluuebunny/crossref_metadata_2025 huggingface dataset:
Male sickle cell patients, compensated transpubertal hypogonadism and normal final growth
Authors: Martins Paulo Roberto Juliano , De Vito Fernanda Bernadelli , Resende Gláucia Aparecida Domingos , Kerbauy José , Pereira Gilberto de Araújo , Moraes‐Souza Helio , Figueiredo Maria Stella , Verreschi Ieda Therezinha
Published: August 2019

Objective

Investigate the gonadal hormonal function in sickle cell individuals.

Context

Sickle cell disease (SCD) is associated with delayed physical and sexual development, and it has been related to both primary testicular failure and hypothalamo‐pituitary‐gonadal axis abnormalities.

Design

The study of the pituitary gonadotrophin reserve was done evaluating the hormonal levels before and after stimulation by gonadoliberin.

Patients

Male patients with homozygous SCD (18‐39 years, median = 29.5 years).

Measurements

Gonadal function was evaluated through clinical parameters and the hormonal quantification.

Results

Although low body weight and other clinical signs of undernutrition such as clinical hypoandrogenism and the extreme retardation of puberty were seen in these patients, final stature and hormonal testicular reserve to hCG stimulation were proved to be normal according to our previous data. In the present investigation, the basal luteotropic gonadotropin (LH), follicle‐stimulating hormone (FSH) and testosterone (T) levels were similar between the patients and controls. Prostate‐specific antigen (PSA) levels—used as a biochemical marker of androgenicity, mainly in puberty—were lower in the patients than in the controls and were only correlated with T. A subtle abnormality in the pituitary responsivity to gonadotropin‐releasing hormone (GnRH) was disclosed, with a higher response to LH 60 minutes after stimulation in patients than in controls.

Conclusions

These data, in addition to both the clinical and biochemical signs of hypoandrogenism associated with normal to elevated T levels strongly suggest a peripheral origin of hypogonadism, which is probably due to androgen resistance in the patients with SCD.
DO MANAGERS MATTER: EVIDENCE FROM E‐SPORTS
Authors: Coates Dennis , Parshakov Petr , Paklina Sofia
Published: August 2019

Growing importance of human resources places the role of managers at the core of company efficiency. However, there are studies that demonstrate the efficiency of teams without a manager, so‐called self‐managed teams, is higher comparing with managed teams. Thus, despite the focus on managerial efficiency in the economic literature, the issue of whether a team needs a manager is far from settled. In this paper, we use a quasi‐experimental setting from e‐Sports (competitive video gaming) to understand whether the hiring a manager is of benefit to team performance. The empirical part of the study is based on endogenous switching regression model. This method allows investigating what performance of self‐managed team would be if it will have a manager and vice versa. The dataset includes the information of prize money and features of top e‐Sports teams in Counter‐Strike: Global Offensive (e‐Sports discipline) from 2013 to 2017. The main finding of this study is that managed teams perform better than self‐managed ones but this is not due to the manager. (JEL Z2, M54, L25)
Impact of angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria
Authors: Coleman C. I. , Weeda E. R. , Kharat A. , Bookhart B. , Baker W. L.
Published: August 2019

Aim

To assess the impact of angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers on renal and mortality outcomes in people with Type 2 diabetes and proteinuria.

Methods

A literature search up to 6 June 2019 was performed. We included randomized trials of ≥100 participants with Type 2 diabetes and micro‐ or macroalbuminuria comparing an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker with placebo ± background anti‐hypertensives or non‐angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker‐containing anti‐hypertensives, which included follow‐up of ≥12 months. Endpoints included doubling of serum creatinine, end‐stage renal disease, all‐cause and cardiovascular mortality and progression and regression of proteinuria. A Hartung‐Knapp random‐effects model (between‐study variance calculated using the Paule‐Mandel estimator) producing a risk ratio with 95% confidence interval was employed.

Results

The use of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker was not associated with a significant reduction in the risk of a doubling in serum creatinine (n = 7 trials, RR = 0.77, 95% CI = 0.50–1.21). Angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers reduced the risk of progressing to end‐stage renal disease (n = 8, RR = 0.79, 95% CI = 0.75–0.83). No difference in all‐cause (n = 11, RR = 0.98, 95% CI = 0.89–1.08) or cardiovascular mortality (n = 6 trials, RR = 1.08, 95% CI = 0.92–1.28), nor the composite outcome of doubling in serum creatinine, end‐stage renal disease or mortality (n = 3 trials, RR = 0.87, 95% CI = 0.72–1.06), was observed. Progression of proteinuria was decreased with angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker use vs. control (n = 10, RR = 0.49, 95% CI = 0.33–0.74). Regression of proteinuria was not improved with an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker (n = 11, RR = 1.55, 95% CI = 0.93–2.58).

Conclusion

Angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers may reduce the risk of end‐stage renal disease and slow the progression of nephropathy, but they do not appear to decrease all‐cause or cardiovascular mortality in people with Type 2 diabetes and proteinuria.
The role of social and/or ecological contexts influences assessment strategy use in Tilapia
Authors: Stienecker Sara L. , Jackson Kelly M. , Moore Paul A.
Published: August 2019

Animals engage in costly agonistic contests during which winners procure resources. During these interactions, the combatants obtain and use information to make decisions on whether to persist or to withdraw from the fight, which is termed assessment. Recent theory and work have suggested that the types of assessment employed may be more variable than previously thought, with the use of different strategies possibly being influenced by social and ecological conditions during priming. This study addresses the contextual components (social and ecological) that affect the utilization of one assessment strategy over another. Male tilapia were primed with different combinations of social (large and small animals) and ecological (resource rich or poor) contexts 24 hr prior to fighting in staged, dyadic contests. When opponents were primed with the same context, a clear assessment strategy emerged and differed as a function of priming treatment. Conversely, when fish were primed with different treatment contexts, there was no discernible assessment. In addition, priming conditions had differing effects for large and small fish. Thus, assessment strategies in cichlids are dependent upon a combination of social, ecological contexts and size of the animal. Since assessment strategies change as a function of both of these contexts, as well as others, future framework investigating assessment strategies should include both intrinsic and extrinsic factors that may shape fighting dynamics.
Proteolytic and nonproteolytic activation mechanisms result in conformationally and functionally different forms of coagulation factor XIII A
Authors: Anokhin Boris A. , Dean William L. , Smith Kerrie A. , Flick Matthew J. , Ariëns Robert A. S. , Philippou Helen , Maurer Muriel C.
Published: August 2019

Factor XIIIA (FXIIIA) is a transglutaminase that cross‐links intra‐ and extracellular protein substrates. FXIIIA is expressed as an inactive zymogen, and during blood coagulation, it is activated by removal of an activation peptide by the protease thrombin. No such proteolytic FXIIIA activation is known to occur in other tissues or the intracellular form of FXIIIA. For those locations, FXIIIA is assumed instead to undergo activation by Ca2+ ions. Previously, we demonstrated a monomeric state for active FXIIIA. Current analytical ultracentrifugation and kinetic experiments revealed that thrombin‐activated FXIIIA has a higher conformational flexibility and a stronger affinity toward glutamine substrate than does nonproteolytically activated FXIIIA. The proteolytic activation of FXIIIA was further investigated in a context of fibrin clotting. In a series of fibrin cross‐linking assays and scanning electron microscopy studies of plasma clots, the activation rates of FXIIIA V34X variants were correlated with the extent of fibrin cross‐linking and incorporation of nonfibrous protein into the clot. Overall, the results suggest conformational and functional differences between active FXIIIA forms, thus expanding the understanding of FXIIIA function. Those differences may serve as a basis for developing therapeutic strategies to target FXIIIA in different physiological environments.

Enzymes

Factor XIIIA ( EC 2.3.2.13)
The carrying capacity for species richness
Authors: Storch David , Okie Jordan G.
Published: August 2019

The idea that the number of species within an area is limited by a specific capacity of that area to host species is old yet controversial. Here, we show that the concept of carrying capacity for species richness can be as useful as the analogous concept in population biology. Many lines of empirical evidence indicate the existence of limits of species richness, at least at large spatial and phylogenetic scales. However, available evidence does not support the idea of diversity limits based on limited niche space; instead, carrying capacity should be understood as a stable equilibrium of biodiversity dynamics driven by diversity‐dependent processes of extinction, speciation and/or colonization. We argue that such stable equilibria exist even if not all resources are used and if increasing species richness increases the ability of a community to use resources. Evaluating the various theoretical approaches to modelling diversity dynamics, we conclude that a fruitful approach for macroecology and biodiversity science is to develop theory that assumes that the key mechanism leading to stable diversity equilibria is the negative diversity dependence of per‐species extinction rates, driven by the fact that population sizes of species must decrease with an increasing number of species owing to limited energy availability. The recently proposed equilibrium theory of biodiversity dynamics is an example of such a theory, which predicts that equilibrium species richness (i.e., carrying capacity) is determined by the interplay of the total amount of available resources, the ability of communities to use those resources, environmental stability that affects extinction rates, and the factors that affect speciation and colonization rates. We argue that the diversity equilibria resulting from these biodiversity dynamics are first‐order drivers of large‐scale biodiversity patterns, such as the latitudinal diversity gradient.
From organised anarchy to de‐coupled bureaucracy: The transformation of university organisation
Authors: Maassen Peter , Stensaker Bjørn
Published: August 2019

Based on key governance and organisational characteristics from the 1970s universities have been conceptualised as organised anarchies and loosely coupled systems. More recently, a number of studies have argued that universities have been changing their internal governance and organisational structures leading to tighter vertical steering and the emergence of more integrated organisations. In this article, it is argued that while tighter vertical integration indeed might be observed, this does not necessarily imply greater horizontal integration in university organising as well. By drawing on case studies of five research‐intensive universities in five different countries, we discuss how strengthened hierarchical governance is driving increased organisational specialisation and professionalisation, but that this also may result in horizontal de‐coupling within universities. The article ends by a discussion of the positive and negative implications of coupled, de‐coupled and loosely coupled organisations.
CEO power and audit fees: Evidence from Malaysia
Authors: Tee Chwee Ming
Published: August 2019

This study examines the association between chief executive officer (CEO) power and audit fees, and whether this association is influenced by family ownership and political connections. The results show that CEO power is associated with lower audit fees, consistent with alignment incentive effect. However, this relationship is attenuated by political connections and family ownership. Whereas the overall findings suggest that audit fees are affected by CEO power, its association is largely influenced by key institutional settings in an emerging market setting.
Exploring factors motivating entrepreneurial intentions: the case of Italian university students
Authors: Ferri Luca , Ginesti Gianluca , Spano Rosanna , Zampella Annamaria
Published: August 2019

This study aims to identify the factors motivating the intentions of university students to become entrepreneurs. Leveraging data from a survey of 941 Italian students and adopting Ajzen's theory of planned behaviour, this paper employs the structural equation model to identify factors explaining students’ entrepreneurial intentions. The findings show that attitudes, subjective norms and perceived behavioural control positively shape Italian students’ intentions. Moreover, the findings signal that the skills acquired during the university pathway play a crucial role in encouraging students to consider entrepreneurial choices. The paper extends and complements the academic and policy debate in the field of entrepreneurship offering a comprehensive investigation of the factors affecting entrepreneurial intentions. It also allows us to contend that higher education may have an important role to play in fostering the entrepreneurial intentions of young people. This is especially significant given current global economic conditions and the renewed importance of self‐employment strategies.
Parenting and child behaviour as predictors of toothbrushing difficulties in young children
Authors: Berzinski Mikaela , Morawska Alina , Mitchell Amy E. , Baker Sabine
Published: August 2019

Background

Oral disease is one of the most prevalent chronic health conditions affecting children. Twice‐daily toothbrushing is recommended to promote good oral health; however, a large proportion of Australian families are not meeting this recommendation.

Aim

This study aimed to identify important barriers to regular toothbrushing for young children.

Design

In this study, 239 parents of 0‐ to 4‐year‐old children completed an online survey that investigated child, family, and parent factors associated with child toothbrushing. Hierarchical linear regression was used to identify predictors of toothbrushing frequency in children and perceived difficulty of the task by parents.

Results

We found that parent factors, specifically oral health knowledge, were the most significant predictors of toothbrushing frequency. Conversely, parent factors did not contribute significantly to the prediction of perceived difficulty of toothbrushing once family and child factors were taken into account. Oral health knowledge and use of routines were identified as the most important predictors of toothbrushing frequency, whereas resistant child behaviour and household organisation were found to be the most important predictors of perceived difficulty of regular toothbrushing.

Conclusions

The findings of the study have implications for behavioural interventions to support parents, as well as directions for future research.
Elephants for Africa: male Savannah elephant Loxodonta africana sociality, the Makgadikgadi and resource competition
Authors: Evans K. E.
Published: August 2019

The resurgence of the Boteti River, at the western border of the Makgadikgadi Pans National Park (MPNP), has had a large influence on the importance of this area in the framework of ecosystem conservation in Botswana and, in particular, for the movement of elephants into historical rangelands. The River represents a hard border to the MPNP and community lands to the east. Cultural knowledge about how to deal with elephants is deficient because of the lack of recent exposure to this species, aggravating the issues in the region. Working towards human–elephant coexistence, Elephants for Africa's research focuses on the social and ecological requirements of male Savannah elephants Loxodonta africana, alongside those of the human population, and applies this in the context of human–wildlife resource competition in the region. Strong partnerships with the communities bordering the MPNP and engaging a local non‐governmental organization board of experts to guide our work are the foundation of evolving working solutions to decrease the socio‐economic impacts of living alongside elephants. The Boteti River and the MPNP constitute a key area for the long‐term sustainability of populations of large mammalian species, including elephants.
The role of diffusion behavior on the formation and evolution of the core‐shell structure in BaTiO3‐based ceramics
Authors: Chen Cheng , Hao Hua , Cui Jingjing , Yu Cong , Tang Yingfei , Cao Minghe , Yao Zhonghua , Wan Baoquan , Liu Hanxing
Published: August 2019

In this work, the influence of starting particle size and sintering conditions on the microstructures and dielectric properties of BaTiO3‐based ceramics coated with 0.3Bi(Zn1/2Ti1/2)O3‐0.7BaTiO3 were investigated to reveal the core‐shell structure by using high resolution transmission electron microscopy technique coupled with energy‐dispersive spectrometer analysis. The ion‐diffusion behavior plays a critical role in the formation and evolution of the core‐shell structure and, therefore, significantly influences the dielectric properties. When using starting powders containing BaTiO3 particles larger than 100 nm in size and sintering for shorter dwelling times (0.5‐2.0 hours), a core‐shell structure could be formed and retained owing to the limited diffusion behavior, enabling BaTiO3‐based ceramics to meet the X8R specification for multilayer ceramic capacitors applications at high temperatures. However, when using 80 nm BaTiO3 nanopowders and further extending the dwelling time to 6.0 hours, more driving energy was provided to prompt ion diffusion, which led to the compositional inhomogeneity becoming homogenized.
Tildrakizumab efficacy and impact on quality of life up to 52 weeks in patients with moderate‐to‐severe psoriasis: a pooled analysis of two randomized controlled trials
Authors: Blauvelt A. , Sofen H. , Papp K. , Gooderham M. , Tyring S. , Zhao Y. , Lowry S. , Mendelsohn A. , Parno J. , Reich K.
Published: August 2019

Background

Two randomized controlled trials (reSURFACE 1 and 2) have demonstrated the effectiveness of tildrakizumab, a high‐affinity, humanized, IgG1κ, anti‐interleukin‐23 monoclonal antibody, for treating moderate‐to‐severe plaque psoriasis in the first 28 weeks.

Objectives

To examine the efficacy of tildrakizumab and its impact on quality of life (QoL) in patients with different levels of week‐28 Psoriasis Area and Severity Index (PASI) improvement.

Methods

Patients treated with tildrakizumab 100 mg or 200 mg from baseline to week 28 were pooled from reSURFACE 1 and reSURFACE 2 and classified into five mutually exclusive week‐28 PASI improvement groups for each dose: PASI 0–49, 50–74, 75–89, 90–99 and 100. Mean PASI improvement and Dermatology Life Quality Index (DLQI) 0/1 over time were examined for each group.

Results

Of 1156 patients, 575 were in the 100‐mg and 578 in the 200‐mg cohorts, respectively. At week 28, 8.3%, 14.3%, 23.8%, 30.4% and 23.1% in the 100‐mg and 4.0%, 18.1%, 19.6%, 29.1% and 29.3% in the 200‐mg cohort achieved PASI < 50, 50–74, 75–89, 90–99 and 100, respectively. Patients with PASI < 50 at week 28 could be identified as early as week 8, and those with week‐28 PASI ≥ 90 had approximately 50% PASI improvement by week 4. Among patients achieving PASI > 50 at week 28 who continued the same dose of tildrakizumab to week 52, mean PASI improvement was maintained or improved over time. Similar results were observed for both doses. Higher proportions of patients achieved DLQI 0/1 in higher week‐28 PASI groups, and DLQI 0/1 was maintained or improved to week 52. However, not all patients with PASI 100 had DLQI 0/1.

Conclusion

Patients unlikely to respond to tildrakizumab could be identified by week 8, and those likely to achieve a PASI ≥ 90 response could be identified as early as week 4. Week‐28 PASI improvement level correlated with QoL improvement.
Characteristics of shared decision making in Romania from the patient perspective: A cross‐sectional multicentric study
Authors: Baicus Cristian , Balanescu Paul , Zeh Stefan , Oprisan Emilia , Lapadatu Rozalina , Gurghean Adriana , Padureanu Vlad , Rezus Ciprian , Mitu Florin , Jurcut Ruxandra , Balanescu Andra Rodica , Daha Ioana , Balanescu Eugenia , Bojinca Mihai , Pinte Larisa , Constantin Alexandru Marian , Dima Nicoleta , Floria Mariana , Leon‐Constantin Maria Magdalena , Roca Mihai , Mitu Magda , Chiriac Silvia , Badescu Codruta Minerva , Ionescu Simona Daniela , Mitrea Elena , Rosu Gabriel , Rezus Elena , Ionescu Georgeta Daniela , Visinescu Ana Maria , Mihailescu Gabriela , Badea Camelia Georgeta
Published: August 2019

Background

Shared decision making (SDM) is very important from patients' perspective. This process has not yet been evaluated in Romania. The study aims to evaluate SDM from the patients' perspective and to evaluate patients' characteristics that associate with SDM.

Material and methods

A cross‐sectional multicentric study comprising eight recruitment centres was performed. Inpatients and outpatients who referred to Hospital Units treating autoimmune diseases or atrial fibrillation were included. Another sample consisted of members of the Autoimmune Disease Patient Society, who completed an online anonymous questionnaire. All participants completed the Romanian translated version of the 9‐item Shared Decision Making Questionnaire (SDM‐Q‐9), as these samples were used for the validation of this questionnaire, too. Patients had to refer to the visit in which the decision concerning the antithrombotic treatment was taken (atrial fibrillation patients), or the immunosuppressive treatment was last time changed (autoimmune disease patients). Ordinal regression having the total SDM score as dependent variable was used.

Results

A total of 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The median score for SDM was 34 of 45, but it differed between hospital completion –39/45 and online completion (anonymous) –20/45 (P < .001). Patients with higher education were influenced most by the setting, giving the best marks in hospital and low marks online, while those with lower education gave lower marks in both settings. In ordinal regression with SDM score as dependent variable, hospital completion of the questionnaire (OR = 9.5, 95% confidence interval, 5.69‐16), collagen disease diagnosis (OR = 2.4, 95% confidence interval, 1.39‐4.14), and immunosuppressive treatment (OR = 2.16, 95% confidence interval, 1.43‐3.26) were independent predictors.

Conclusion

In our study, full anonymity was associated with significantly lower scores for the SDM process. The patients with higher education were most influenced by this condition, while those with the lowest education were the most critical.
Life Cycles of Myxogastria Stemonitopsis typhina and Stemonitis fusca on Agar Culture
Authors: Dai Dan , Okorley Benjamin A. , Li Yu , Zhang Bo
Published: August 2019

Myxogastria is a group of protozoa characterized by cellular uninucleate amoeboflagellates (myxamoebae and flagellated swarm cell), acellular multinucleate plasmodia, and stationary spore‐bearing sporocarps. The Stemonitales is a large order in the Myxogastria and contains approximately 230 species, but only 13 species have their completed life cycles observed so far. Here, we described the life cycles of two species in Stemonitales, Stemonitopsis typhina and Stemonitis fusca by culturing in water agar medium and observing the morphogenesis of their spore germination, plasmodium, and sporocarp development. The spore‐to‐spore life cycles of Ste. typhina and S. fusca were completed in approximately 67 and 12 d, respectively. Both species possessed an aphanoplasmodium. However, the spores of Ste. typhina and S. fusca germinated by the V‐shape split and pore methods, respectively. Unlike S. fusca with an evanescent peridium, Ste. typhina produced a shiny persistent peridium which was continuous with the membrane surrounding its stalk. The information will contribute to a better understanding of their taxonomy and phylogeny.
Influence of life‐style factors, including second‐hand smoke, on dental caries among 3‐year‐old children in Wuxi, China
Authors: Tang Shai‐Di , Zhang Yan‐Xiao , Chen Li‐Mei , Wang Yue‐Yan , Cheng Yang , Tang Li‐Qin
Published: August 2019

Aim

To examine the association of life‐style factors, including second‐hand smoke, with dental caries among 3‐year‐old children in Wuxi, China.

Methods

A multi‐stage stratified random cluster sampling method was used, and 283 children were recruited. The prevalence of dental caries was 29.3% (83/283).

Results

Univariate analysis indicated that the possible related factors of dental caries included sleep duration, interest in snacks, candy, exposure to second‐hand smoke and weight of birth (all P < 0.05). Meanwhile, multivariate logistic regression analysis suggested that children who had used fluoride were less susceptible to dental caries than those who had not used fluoride before (P < 0.05). Moreover, the risk of dental caries in children who were very interested in snacks was greater than those with little interest in snacks (P < 0.05).

Conclusions

Life‐style behaviours are crucial factors and should attract enough attention. There might be a potential negative effect of second‐hand smoke on the deciduous caries, but it still requires further studies. A co‐ordinated effort by health‐care providers, policymakers and health institutions has successfully improved children's oral health and the awareness of hygiene knowledge among citizens in Wuxi city.
The effects of copper on photosynthesis and biomolecules yield in Chlorolobion braunii
Authors: Baracho Douglas H. , Silva Jaqueline C. , Lombardi Ana T.
Published: August 2019

Our knowledge of the effects of copper on microalgal physiology is largely based on studies conducted with high copper concentrations; much less is known when environmentally relevant copper levels come into question. Here, we evaluated the physiology of Chlorolobion braunii exposed to free copper ion concentrations between 5.7 × 10−9 and 5.0 × 10−6 mol · L−1, thus including environmentally relevant values. Population growth and maximum photosynthetic quantum yield of PSII were determined daily during the 96 h laboratory controlled experiment. Exponentially‐growing cells (48 h) were analyzed for effective quantum yield and rapid light curves (RLC), and total lipids, proteins, carbohydrates, chlorophyll a and carotenoids were determined. The results showed that growth rates and population density decreased gradually as copper increased in experiment, but the photosynthetic parameters (maximum and effective quantum yields) and photochemical quenching (qP) decreased only at the highest free copper concentration tested (5.0 × 10−6 mol · L−1); nonphotochemical quenching (NPQ) increased gradually with copper increase. The RLC parameters Ek and rETRmax were inversely proportional to copper concentration, while α and Im decreased only at 5.0 × 10−6 mol · L−1. The effects of copper in biomolecules yield (mg · L−1) varied depending on the biomolecule. Lipid yield increased at free copper concentration as low as 2.5 × 10−8 mol · L−1, but proteins and carbohydrates were constant throughout.
microRNA‐206 modulates the hepatic expression of the organic anion‐transporting polypeptide 1B1
Authors: El Saadany Tämer , van Rosmalen Belle , Gai Zhibo , Hiller Christian , Verheij Joanne , Stieger Bruno , van Gulik Thomas , Visentin Michele , Kullak‐Ublick Gerd A.
Published: August 2019

Background & Aims

The organic anion‐transporting polypeptide 1B1 (OATP1B1) is an anion exchanger expressed at the hepatocyte sinusoidal membrane, which mediates the uptake of several endogenous metabolites and drugs. OATP1B1 expression level and activity are major sources of inter‐patient variability of pharmacokinetics and pharmacodynamics of several drugs. Besides the genotype, factors that contribute to the inter‐individual variability in OATP1B1 expression level are practically unknown. The aim of this work was to uncover novel epigenetic mechanisms of OATP1B1 regulation.

Methods

A functional screening strategy to assess the effect of microRNAs on the uptake of estrone‐3‐sulphate, an OATP1B1 substrate, into human hepatocellular carcinoma (Huh‐7) cells was used. microRNA‐206 (miR‐206) expression in human liver tissues was measured by real‐time RT‐PCR. OATP1B1 expression in Huh‐7 and in human liver tissues was assessed by real‐time RT‐PCR, Western blotting and immunostaining. The mRNA‐miRNA interaction was assessed by reporter assay.

Results

miR‐206 mimic repressed mRNA and protein expression of OATP1B1 in Huh‐7 cells. The intracellular accumulation of estrone‐3‐sulphate was reduced by 30% in cells overexpressing miR‐206. The repressive effect of miR‐206 on the activity of the firefly luciferase gene 2 under the control of the OATP1B1 3’ untranslated region was lost upon deletion of the predicted miR‐206 binding site. Hepatic miR‐206 level negatively correlated with OATP1B1 mRNA and protein levels extracted from normal human liver tissues.

Conclusions

miR‐206 exerts a suppressive effect on OATP1B1 expression by an epigenetic mechanism. Individuals with high hepatic levels of miR‐206 appear to display lower level of OATP1B1.
The autologous pubovaginal fascial sling: An update in 2019
Authors: Plagakis Sophie , Tse Vincent
Published: August 2019

The contemporary management of stress urinary incontinence (SUI) has seen renewed interest in the use of autologous fascia for the formation of a retropubic suburethral sling. Traditionally, it has been used in only the most severe of incontinence cases, such as those women with intrinsic sphincter deficiency, or in patients requiring concomitant reconstructive procedures. In the current climate surrounding transvaginal mesh, many doctors and patients are shying away from the less morbid synthetic midurethral sling. International literature has demonstrated that the fascial sling is a safe and efficacious procedure for all patients with SUI, adequately treating both urethral hypermobility and intrinsic sphincter deficiency. This paper will discuss the indications, technique, and outcomes of autologous fascial slings. We will explore the use of fascial slings following failed synthetic slings and also the troubleshooting of commonly encountered issues intra‐ and postoperatively.
Efficacy of Tadalafil Therapy and Changes in Oxidative Stress Levels in Male Patients with Lower Urinary Tract Symptoms and Overactive Bladder
Authors: Matsuo Tomohiro , Miyata Yasuyoshi , Araki Kyohei , Mukae Yuta , Otsubo Asato , Ohba Kojiro , Sakai Hideki
Published: August 2019

Objective

To evaluate the effects of tadalafil monotherapy on lower urinary tract symptoms, urodynamic parameters, and oxidative stress levels in male patients.

Methods

This prospective study included 53 male patients with urinary symptoms, who met the criteria for overactive bladder (OAB) (≥ 2 points for Q3 [urgency] in the OAB symptom score [OABSS] assessment and ≥ 3 points for the total score). The patients received 5 mg tadalafil orally once daily, and their symptoms were assessed before and after the 12‐week treatment. The OABSS and international prostate symptom score (IPSS) were used to evaluate the subjective symptoms. The objective findings were assessed using uroflowmetry. Oxidative stress was assessed by determining urinary levels of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) levels with an adjustment for urinary creatinine (CR) concentration.

Results

After tadalafil administration, total and individual indices of the OABSS assessment showed significant improvement. In addition, total storage and voiding symptoms that contributed to the IPSS were also significantly improved. The voided volume was increased, and the maximum flow rate was improved after tadalafil treatment (P = .002 and < 0.001, respectively). Urinary 8‐OHdG/CR decreased from 12.4 ± 9.7 ng/mg CR to 7.6 ± 11.6 ng/mg CR (P < .001). In patients who showed OAB improvement and did not meet the criteria for OAB after the treatment (44 patients, 83.0%), the urinary 8‐OHdG/CR level was significantly decreased from 11.6 ± 8.4 ng/mg CR to 6.4 ± 10.3 ng/mg CR (P < .001).

Conclusions

Tadalafil treatment improves OAB symptoms and urodynamic parameters by decreasing oxidative stress level.
Acute‐subacute paracoccidioidomycosis: A paediatric cohort of 141 patients, exploring clinical characteristics, laboratorial analysis and developing a non‐survival predictor
Authors: Romaneli Mariana Tresoldi das Neves , Tardelli Natália Rocha , Tresoldi Antonia Teresinha , Morcillo André Moreno , Pereira Ricardo Mendes
Published: August 2019

The acute‐subacute form of paracoccidioidomycosis (PCM) is a severe systemic mycosis that affects children and adolescents from endemic regions, leading to generalised lymphadenopathy, fever, weight loss, anaemia, eosinophilia, hypoalbuminemia and hypergammaglobulinemia. The objective of this study is to describe the clinical and laboratorial characteristics of acute‐subacute PCM, to determine a mortality risk factor and to propose a test for non‐survival hazard related to the disease. Children and adolescents diagnosed with PCM, under 15 years were included in the study. Their epidemiological, clinical and laboratorial data were obtained from the hospital records. Descriptive analysis, comparison of means, univariate logistic regression, multivariate logistic regression and a ROC curve were performed in order to identify significant information (P < .05). Through a period of 38 years, 141 children and adolescents were diagnosed with acute‐subacute PCM. The main antifungal agent used for the treatment was sulfamethoxazole‐trimethoprim (SMX‐TMP). The complication rate was 17%, the relapse rate was 7.8% and the mortality rate was 5.7%. A low albumin dosage was identified as a predictor factor for mortality. The cut‐off for serum albumin was 2.18 g/dL, above which, the survival rate is 99.1%. Thus, simple clinical and laboratorial examinations may lead to the diagnosis of acute‐subacute PCM, and the beginning of the treatment is encouraged even before the isolation of the fungus in biological samples, preventing unfavourable outcomes. Patients with an albumin dosage ≤ 2.18g/dL must receive special attention, preferably hospitalised, during the first four weeks of treatment for presenting an elevated mortality hazard.
In vitro activities of 15 antifungal drugs against a large collection of clinical isolates of Microsporum canis
Authors: Abastabar Mahdi , Jedi Ali , Guillot Jacques , Ilkit Macit , Eidi Samaneh , Hedayati Mohammad Taghi , Shokohi Tahereh , Daie Ghazvini Roshanak , Rezaei‐Matehkolaei Ali , Katiraee Farzad , Javidnia Javad , Ahmadi Bahram , Badali Hamid
Published: August 2019

Background

Microsporum canis is a zoophilic species, found to be the most frequently isolated species in animals. M. canis causes sporadic outbreaks of infections in humans, such as the one that occurred in Canada, where more than 1000 human cases were detected over an 8‐year period. Despite the medical importance of M. canis infections, there are limited in vitro data on the antifungal susceptibility to antifungal drugs, including new generation triazoles and imidazoles.

Objective

The aim of the current study was to comprehensively evaluate the in vitro activity of new azoles and comparator drugs against a large panel of M. canis isolates using a microdilution assay.

Methods

The in vitro susceptibility to novel triazoles and imidazoles was compared to that of other antifungal drugs using a large collection of M. canis clinical isolates (n = 208) obtained from patients and animals with dermatophytosis in Iran, France and Turkey.

Results

All isolates exhibited high susceptibility to the majority of the tested antifungal agents. However, luliconazole, lanoconazole and efinaconazole, as well as econazole, demonstrated superior activity against all strains in comparis on with the other drugs.

Conclusion

FDA‐approved antifungal drugs, that is luliconazole, efinaconazole and lanoconazole, showed the highest antifungal activity and should be promising candidates for the treatment of dermatophytosis caused by M canis. However, their therapeutic effectiveness remains to be determined in clinical settings.
Zionist identity and the British Mandate: Palestine's internment camps and the making of the Western native
Authors: Yohanani Lior
Published: August 2019

This paper examines the relationship between British police officers, Jewish guards, and German internees in Palestine's internment camps during World War II. Using the reports of the Jewish guards, the paper investigates the role of Western‐identified actors in the Zionist identity‐making project. The reports evince a surprising rapport between the British and their German prisoners and the mistreatment of the Jewish guards by their British superiors. The paper analyses these Jewish accounts in the context of identity‐ and ethnic boundary‐making and argues that they illustrate Zionism's intent to construct itself as a Western but noncolonial movement and Zionists in Palestine as natives but not “Orientals.” The reports also reveal a breach between the formal hierarchy—British officers, Jewish guards, German internees—and the ethnic order, which situated British and Germans at the apex and the Jews at the bottom. The paper highlights the utility of researching group‐making interactions in different contexts to develop a more nuanced understanding of identity‐making processes.
Co‐existent pilocytic astrocytoma with acute B‐cell leukemia within the cerebellum
Authors: Hickman Richard , Leeman‐Neill Rebecca , Rosenblum Marc , Anderson Richard , Goldman James
Published: August 2019

Pilocytic astrocytomas are the commonest childhood brain tumor. They are typically benign and usually are solitary neoplasms. To our knowledge, only one report of a pilocytic astrocytoma with leukemia has been previously issued. We herein describe the first case with documented histopathology of a 2‐year‐old boy who had a cerebellar pilocytic astrocytoma co‐localized with an acute B‐lymphoblastic leukemia. We speculate that chemotactic migration of leukemic cells to the pilocytic astrocytoma may be partly mediated through vascular endothelial growth factor (VEGF) and VEGF receptors.
Increased number of mitochondria in capillaries distributed in stroke‐like lesions of two patients with MELAS
Authors: Yamadera Misaki , Fujimura Harutoshi , Shimizu Yuri , Matsui Misa , Nakamichi Itsuko , Yokoe Masaru , Sakoda Saburo
Published: August 2019

We investigated two autopsy cases of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) using immunohistochemical staining with an anti‐mitochondrial antibody against translocase of the outer membrane 20 (TOMM20). In case 1, the patient was a 42‐year‐old man with a disease duration of 53 days, and in case 2, the patient was a 62‐year‐old woman with a disease duration of 27 months. In both the cases autopsy revealed moderate atrophy of the cerebrum and cerebellum and multifocal necrotizing lesions, irrespective of the vascular territory. Case 1 showed multiple areas with total necrosis in the cortex, accompanied by increases in number of protoplasmic astrocytes and acidophilic neurons as well as axonal swelling, suggestive of acute or subacute stage stroke‐like lesions (SLLs). In case 2, most of the SLLs displayed laminar spongy change in a rarefied cortex, and were considered to be at the chronic stage. In both the cases, capillary proliferation was noted within the SLLs, particularly in the acute phase. Endothelial cells of proliferating capillaries were strongly positive for TOMM20. In the cortex outside the SLLs, microvessels displayed only a fine granular immunoreactivity, as is seen in the controls. Although smooth muscle cells and endothelial cells in pial arteries and arterioles were also strongly positive for TOMM20, the territories of the affected pial arteries and arterioles did not correlate with the distribution of the SLLs. Although MELAS is characterized by recurrent stroke‐like episodes (SLEs), the pathogenetic relationship between SLEs and mitochondrial angiopathy remains unknown. An aberrant increase of mitochondria in the capillary endothelial cells of SLLs may disturb endothelial function, thus playing a role in the formation or development of SLLs.
Esophageal physiologic profiles within erosive esophagitis in China: Predominantly low‐grade esophagitis with low reflux burden
Authors: Zhang Mengyu , Tan Niandi , Li Yuwen , Chen Minhu , Xiao Yinglian
Published: August 2019

Background & aims

The Lyon Consensus defines LA grades C&D erosive esophagitis (EE) or acid exposure time (AET) >6% as the conclusive evidence for gastro‐esophageal reflux disease (GERD). However, most of EE is LA grade A&B and the rate of AET exceeding 6% is low in China. We aimed to evaluate patients with EE in the Chinese population based on the Lyon Criteria.

Methods

A retrospective study was performed among patients with EE who had esophageal function tests performed in a tertiary hospital from 2013 to 2017. Erosive esophagitis was staged according to the Los Angeles classification. Their motor profiles from high‐resolution manometry (HRM), reflux profiles from multichannel intraluminal impedance‐pH (MII‐pH) monitoring and proton pump inhibitor (PPI) efficacy were analyzed. Patients were categorized as conclusive or inconclusive GERD.

Results

Among 112 patients with EE who underwent esophageal function tests, EE of LA grade C&D was found in only 4.46% (N = 5). Almost 35% (N = 37) of patients with LA grade A&B EE had AET exceeded 6%, who had good PPI response similar to those with LA grade C&D EE (77.42% vs 100%, P = .559). The remaining 70 patients (62.50%) were inconclusive GERD, of whom 56.25% responded to PPI. Inconclusive GERD patients had a wide range (7.14%‐97.14%) of positive adjunctive evidences from HRM and MII‐pH monitoring without significant correlation to PPI response rate.

Conclusions

The reflux burden within patients with EE is predominantly low in China, and adjunctive HRM and MII‐pH profiles from Lyon criteria do not segregate PPI response.
National policies to prevent obesity in early childhood: Using policy mapping to compare policy lessons for Australia with six developed countries
Authors: Esdaile Emma , Thow Anne Marie , Gill Tim , Sacks Gary , Golley Rebecca , Love Penelope , Wen Li Ming , Rissel Chris
Published: August 2019

Interventions for obesity prevention in early childhood (first 5 years of life) are likely to have a significant preventive health impact. This mapping review identified recommended policy options for the Australian Federal Government (AFG) by comparing countries with similar population, income, and language to Australia. Policies were mapped in six countries using two matrices. The first matrix examined policy context, describing obesity prevention governance. The second matrix examined policy content, compared with global recommendations. Policies were grouped into downstream (healthcare), midstream (lifestyle and settings), and upstream (determinants of health, including food and built environments). Results identified variance in obesity governance across the six countries including policy coherence, leadership, institutional drivers, and overlapping responsibility across different levels of government. While countries tended to have more downstream or midstream policies, upstream policies were more likely when countries had invested in system‐wide approaches to obesity such as developing a national obesity strategy, having separate food/nutrition and physical activity plans, and a dedicated preventive health agency. This study recommends a range of initiatives for the AFG to strengthen policies for the prevention of obesity in early childhood, including prioritising the development of a national food/nutrition strategy.
Oral features of systemic sclerosis: A case–control study
Authors: Gomes da Silva Guilherme Soares , Maymone de Melo Marina Lins , Leão Jair Carneiro , Carvalho Alessandra Tavares , Porter Stephen , Duarte Angela Luzia Branco Pinto , Dantas Andrea Tavares , Gueiros Luiz Alcino
Published: August 2019

Objective

The aim of this study was to evaluate the orofacial parameters of systemic sclerosis (SSc) and its related systemic features.

Subjects and Methods

A descriptive case–control study was performed from November 2015 to October 2016. Ninety‐three individuals were included and divided into SSc group (n = 50) and healthy controls (C, n = 43).

Results

Systemic sclerosis individuals were mostly women (43/50, 86%), with a mean age of 46 years (±11.6 years). Telangiectasia (42/50, 84%) and reduced mouth opening (35/50, 70%) were the most frequent orofacial findings. The periodontitis frequency was much higher in SSc individuals than in healthy controls (90.7% × 48.83%; p < .001). In addition, SSc individuals presented a distinctive pattern of periodontitis, with low probing pocket depth (2 ± 0.65 mm × 2 ± 0.24; p < .001), higher gingival recession (4 ± 2.13 × 0.14 ± 0,22; p < .001), higher periodontal attachment loss (6 ± 1.34 mm × 2 ± 0.43, p < .001), and lower gingival bleeding index values (7.05 ± 7.25 × 21.57 ± 15.66; p < .001).

Conclusions

Orofacial manifestations were common in SSc and included a unique pattern of periodontal manifestation, characterized by lower gingival bleeding index, higher periodontal attachment loss, and low probing depth.
Case report series of a novel application of neostigmine to successfully relieve refractory ileus status post‐pediatric orthotopic liver transplantation
Authors: Petersen Pamela C. , Balakrishnan Binod , Vitola Bernadette , Hong Johnny C.
Published: August 2019

Post‐operative ileus is common after abdominal surgeries. Children undergoing liver transplant are at increased risk of ileus for various reasons including multiple abdominal procedures and use of narcotic medications. Ileus can lead to abdominal compartment syndrome and compromise the integrity of the liver graft. In some of these patients, ileus is resistant to standard therapies including stool softeners, bowel stimulants, enemas, and even methylnaltrexone. Neostigmine has been shown in pediatric case series to be efficacious in some children for refractory post‐operative ileus. We report three children (9 months, 3 years, and 12 years old) who developed refractory ileus after liver transplant, with one of them developing abdominal compartment syndrome, who were treated successfully with continuous infusions of neostigmine. Clinical responses included passage of flatus and stool and improvement in abdominal distension. All patients tolerated the infusion without serious adverse effects such as bradycardia or bronchospasm. Neostigmine was used safely in our patients and may be safe and efficacious for the treatment of refractory ileus in pediatric patients after liver transplantation. Neostigmine should be considered early in the treatment of these patients.