bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Correlates of Early-Onset Hypertension
Authors: Suvila Karri , Lima Joao A C , Cheng Susan , Niiranen Teemu J
Published: April 2021

BACKGROUND

Early-onset hypertension has been established as a heritable trait and a risk factor for cardiovascular disease outcomes. However, the clinical correlates of early-onset hypertension remain unidentified.

METHODS

In this study, we assessed the demographic characteristics and lifestyle factors related to hypertension onset age in a sample of 3,286 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean baseline age 25 ± 4 years, 57% women). We examined the association between the participants’ baseline characteristics and age of hypertension onset subgroups (<35, 35‒44, or ≥45 years) using a multinomial logistic regression model with those who did not develop hypertension as the reference group. Hypertension onset was defined as blood pressure ≥140/90 mm Hg or antihypertensive medication use on 2 consecutively attended follow-up visits.

RESULTS

In the multinomial logistic regression model, individuals who were black (odds ratio [OR], 5.08; 95% confidence interval [CI], 3.17–8.14), were more obese (OR, 1.57; 95% CI, 1.32–1.88), or had higher total cholesterol (OR, 1.34; 95% CI, 1.13–1.60 per SD) had increased odds of early-onset hypertension (onset at <35 years) vs. not developing hypertension. In contrast, 1-SD higher high-density lipoprotein (HDL)-cholesterol was related to decreased odds of early-onset hypertension (OR, 0.71; 95% CI, 0.57–0.89). The odds for having earlier hypertension onset increased linearly across age of onset categories in black individuals and individuals with lower HDL-cholesterol (P < 0.05 for trend for both).

CONCLUSIONS

Our findings suggest that individuals who are black, obese, have higher total cholesterol, or have lower HDL-cholesterol level, are potentially at an increased risk of having early-onset hypertension.
Interpretation of coronary steal syndrome and haemodynamic changes after surgical closure of coronary fistula using Doppler wire and computational fluid dynamics analysis: a case report
Authors: Lee Kwan Yong , Chang Kiyuk , Lee Joo Myung , Lee Sang-Wook
Published: April 2021

Background

Coronary arteriovenous fistulas (CAFs) are rare but can cause myocardial ischaemia and other complications. However, the haemodynamic and physiologic characteristics of significant CAFs requiring treatment are poorly described. We report a case of CAF causing coronary steal syndrome in which haemodynamic changes were assessed before and after surgical closure using a Doppler wire and computational fluid dynamics (CFD) technique.

Case summary

A 51-year-old woman presented with exertional chest pain for 3 years. Progressive dyspnoea occurred with exertion. Treadmill and cardiopulmonary exercise tests showed suspicious myocardial ischaemia. Coronary angiography and contrast-enhanced coronary computed tomography angiography (CCTA) revealed a coronary fistula arising from the distal left main coronary artery that drained into the pulmonary artery trunk. We observed a persistent coronary steal phenomenon at baseline and during hyperaemia and a systolic dominant flow rate pattern inside the CAF by Doppler wire-based flow rate measurement. According to CFD analysis based on CCTA, low wall shear stress and a high focal oscillatory shear index were observed at the ostial sites of aneurysmal sacs in the CAF. After successful surgical closure of the CAF, the vessel sizes and flow rate distributions of the coronary arteries increased.

Discussion

Doppler wire-based flow rate distribution measurements and CFD analysis may facilitate the identification of significant coronary steal syndrome requiring closure and the evaluation of future risks of life-threatening complications such as thrombosis and rupture.
Large-Scale Annotation and Evolution Analysis of MiRNA in Insects
Authors: Ma Xingzhou , He Kang , Shi Zhenmin , Li Meizhen , Li Fei , Chen Xue-Xin
Published: April 2021

Insects are among the most diverse and successful groups of animals and exhibit great morphological diversity and complexity. The innovation of wings and metamorphosis are some examples of the fascinating biological evolution of insects. Most microRNAs (miRNAs) contribute to canalization by conferring robustness to gene networks and thus increase the heritability of important phenotypes. Though previous studies have demonstrated how miRNAs regulate important phenotypes, little is still known about miRNA evolution in insects. Here, we used both small RNA-seq data and homology searching methods to annotate the miRNA repertoires of 152 arthropod species, including 135 insects and 17 noninsect arthropods. We identified 16,212 miRNA genes, and classified them into highly conserved (62), insect-conserved (90), and lineage-specific (354) miRNA families. The phylogenetic relationship of miRNA binary presence/absence dynamics implies that homoplastic loss of conserved miRNA families tends to occur in far-related morphologically simplified taxa, including scale insects (Coccoidea) and twisted-wing insects (Strepsiptera), leading to inconsistent phylogenetic tree reconstruction. The common ancestor of Insecta shares 62 conserved miRNA families, of which five were rapidly gained in the early winged-insects (Pterygota). We also detected extensive miRNA losses in Paraneoptera that are correlated with morphological reduction, and miRNA gains in early Endopterygota around the time holometabolous metamorphosis appeared. This was followed by abundant miRNA gains in Hymenoptera and Lepidoptera. In summary, we provide a comprehensive data set and a detailed evolutionary analysis of miRNAs in insects. These data will be important for future studies on miRNA functions associated with insect morphological innovation and trait biodiversity.
Androgen Receptor Modulates Multimodal Displays in the Bornean Rock Frog (Staurois parvus)
Authors: Smith Sarah M , Eigerman Amelia R , LeCure Kerry M , Kironde Eseza , Privett-Mendoza Auxenia Grace , Fuxjager Matthew J , Preininger Doris , Mangiamele Lisa A
Published: April 2021

Synopsis

Multimodal communication is common in the animal kingdom. It occurs when animals display by stimulating two or more receiver sensory systems, and often arises when selection favors multiple ways to send messages to conspecifics. Mechanisms of multimodal display behavior are poorly understood, particularly with respect to how animals coordinate the production of different signals. One important question is whether all components in a multimodal display share an underlying physiological basis, or whether different components are regulated independently. We investigated the influence of androgen receptors (ARs) on the production of both visual and vocal signal components in the multimodal display repertoire of the Bornean rock frog (Staurois parvus). To assess the role of AR in signal production, we treated reproductively active adult males with the antiandrogen flutamide (FLUT) and measured the performance of each component signal in the multimodal display. Our results show that blocking AR inhibited the production of multiple visual signals, including a conspicuous visual signal known as the “foot flag,” which is produced by rotating the hind limb above the body. However, FLUT treatment caused no measurable change in vocal signaling behavior, or in the frequency or fine temporal properties of males’ calls. Our study, therefore, suggests that activation of AR is not a physiological prerequisite to the coordination of multiple signals, in that it either does not regulate all signaling behaviors in a male’s display repertoire or it does so only in a context-dependent manner.
Evolving factors influencing consumers’ attitudes towards the use of eHealth applications: implications on the future of Neom
Authors: Algumzi Areej
Published: April 2021

Background

Factors affecting the adoption and use of eHealth applications have been extensively researched from different perspectives in different regions. However, with the changing circumstances (e.g. the coronavirus disease 2019 pandemic), new influencing factors might evolve and can influence the attitudes of consumers towards using eHealth applications. The purpose of this study was to identify and evaluate the evolving factors affecting consumer attitudes towards the use of eHealth applications and provide implications for the future of Neom.

Methods

An online survey questionnaire was used to collect data from 976 eHealth consumers in Saudi Arabia, which included 527 male and 449 female participants. Findings were analysed using the statistical means and standard deviations for each item in the questionnaire to analyse the role of each factor in depth. Statistical t-tests were used to identify significant differences between the groups categorised by age and gender.

Results

‘Necessity but not interest’ (mean 4.5 [standard deviation {SD} 1.12]) and fear (mean 4.5 [SD 1.13]) and psychological factors including depression (mean 4.4 [SD 1.54]), stress (mean 4.2 [SD 1.09]) and anxiety (mean 4.3 [SD 1.61]) were identified to be major evolving influencing factors, while other factors including performance expectancy, ease of use, enjoyment and incentives were identified to be comparatively less influential.

Conclusions

Increasing adoption of eHealth mainly due to necessity but not out of interest can have serious implications for patients and the adoption of eHealth technologies in the future.
An HIV Primary Care Rotation Improved HIV and STI Knowledge, Enhanced Sexual History-Taking Skills, and Increased Interest in a Career in Infectious Diseases Among Medical Students and Residents
Authors: Marshall Austin A , Wooten Darcy A
Published: April 2021

Rotations in HIV primary care clinics have the potential to teach trainees core competencies and influence their career pathway. We found that fund of knowledge, confidence in obtaining a sexual history, and interest in an Infectious Diseases career all increased following an HIV clinic rotation.
Effect of Exercise Involving Standing Weight Shifting to the Nonparetic Side on an Inclined Surface in the Early Phase After a Stroke: A Randomized Controlled Trial
Authors: Inoue Masahide , Amimoto Kazu , Chiba Yuya , Sekine Daisuke , Fukata Kazuhiro , Fujino Yuji , Takahashi Hidetoshi , Makita Shigeru
Published: April 2021

Objective

This study aimed to clarify whether an exercise involving weight shifting to the nonparetic side while standing on an inclined surface improves standing balance in the early phase after stroke.

Methods

This assessor-blinded, randomized controlled trial included people undergoing inpatient rehabilitation at a university hospital. Participants (N = 52) with hemiparesis caused by a stroke were randomly assigned to an experimental group (n = 26) or control group (n = 26). Participants performed a weight-shifting exercise to the nonparetic side using a goal-directed reaching strategy while standing on an inclined surface that was elevated 5 degrees to the nonparetic side in the experimental group or a flat surface in the control group. The reaching exercise was conducted 30 times per day for 5 days. Primary outcome was the Berg Balance Scale. Secondary outcomes were the posturographic examination (static standing and lateral weight shifting to the nonparetic and paretic sides), Trunk Control Test, Trunk Impairment Scale, Functional Ambulation Category, and Functional Independent Measure motor item scores.

Results

Through intention-to-treat analysis, no significant intervention effects were observed between groups on the Berg Balance Scale. A significant intervention effect was observed, however, with the experimental group on the lateral weight shifting to the nonparetic side in the mean percentage bodyweight values and center-of-pressure moving distance and to the paretic side in center-of-pressure moving distance and Functional Ambulation Category. There were no significant interaction effects concerning other outcomes.

Conclusion

These results suggest that standing reaching exercises to the nonparetic side while standing on an inclined surface could improve lateral weight-shifting capacity and gait ability in participants in the early poststroke phase.

Impact

This intervention should be incorporated into standard treatment programs focusing on the paretic side during early stroke rehabilitation.
Novel biomarkers for glycaemic deterioration in type 2 diabetes: an IMI RHAPSODY study
Authors: Slieker Roderick C , Donnelly Louise A , Lopez-Noriega Livia , Muniangi-Muhitu Hermine , Akalestou Elina , Sheikh Mahsa , Georgiadou Eleni , Giordano Giuseppe N. , Åkerlund Mikael , Ahlqvist Emma , Ali Ashfaq , Barovic Marko , Bouland Gerard A , Burdet Frédéric , Canouil Mickaël , Dragan Iulian , Elders Petra JM , Fernandez Celine , Festa Andreas , Fitipaldi Hugo , Froguel Phillippe , Gudmundsdottir Valborg , Gudnason Vilmundur , Gerl Mathias J. , van der Heijden Amber A , Jennings Lori L , Hansen Michael K. , Kim Min , Leclerc Isabelle , Klose Christian , Kuznetsov Dmitry , Aly Dina Mansour , Mehl Florence , Marek Diana , Melander Olle , Niknejad Anne , Ottosson Filip , Pavo Imre , Efanov Alexander , Duffin Kevin , Pullen Timothy J. , Simons Kai , Solimena Michele , Suvitaival Tommi , Wretlind Asger , Rossing Peter , Lyssenko Valeriya , Quigley Cristina Legido , Groop Leif , Thorens Bernard , Franks Paul W , Ibberson Mark , Beulens Joline WJ , ’t Hart Leen M , Pearson Ewan R , Rutter Guy A
Published: April 2021

We have deployed a multi-omics approach in large cohorts of patients with existing type 2 diabetes to identify biomarkers for disease progression across three molecular classes, metabolites, lipids and proteins. A Cox regression analysis for association with time to insulin requirement in 2,973 patients in the DCS, ANDIS and GoDARTS cohorts identified homocitrulline, isoleucine and 2-aminoadipic acid, as well as the bile acids glycocholic and taurocholic acids, as predictive of more rapid deterioration. Increased levels of eight triacylglycerol species, and lowered levels of the sphingomyelin SM 42:2;2 were also predictive of disease progression. Of ∼1,300 proteins examined in two cohorts, levels of GDF-15/MIC1, IL-18RA, CRELD1, NogoR, FAS, and ENPP7 were associated with faster progression, whilst SMAC/DIABLO, COTL1, SPOCK1 and HEMK2 predicted lower progression rates. Strikingly, identified proteins and lipids were also associated with diabetes incidence and prevalence in external replication cohorts. Implicating roles in disease compensation, NogoR/RTN4R improved glucose tolerance in high fat-fed mice and tended to improved insulin signalling in liver cells whilst IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. Conversely, high NogoR levels led to islet cell apoptosis. This comprehensive, multi-disciplinary approach thus identifies novel biomarkers with potential prognostic utility, provides evidence for new disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
Traumatic dislocation of the eye into the maxillary sinus: Case report and literature review
Authors: Vránová Kateřina , Chytilová Karin , Dobiáš Martin , Tvrdý Peter , Handlos Petr
Published: April 2021

Traumatic dislocation of the eye is usually encountered in high‐energy injuries. These include traffic accidents, accidents at work, sporting accidents, falling from a height, impact of the hooves or horns of animals, gunshot injuries, and physical assault. Such incidents are accompanied by facial soft tissue damage and injuries to the facial skeleton, especially the orbit, and can be associated with varying degrees of dislocation of the eye. We describe a rare case of non‐fatal traumatic eye dislocation into the maxillary sinus, coupled with an orbital fracture resulting from a physical assault on a 63‐year‐old woman. The cause of death was asphyxiation due to manual strangulation and mechanical asphyxia. Even though dislocations of the eye are relatively rare, forensic pathologists should be aware of such injuries to correct assessment of injury mechanism. The available literature regarding eye dislocation is summarized, and the forensic issues applicable to the assessment of such cases are reviewed.
Uterine natural killer cells and recurrent spontaneous abortion
Authors: Fu Yao‐Yao , Ren Chun‐E. , Qiao Peng‐Yun , Meng Yu‐Han
Published: April 2021

Recurrent spontaneous abortion (RSA), termed as two or more consecutive pregnancy loss is a great problem for some women of childbearing age. A large number of evidence confirm that there may be an immune background of RSA. As a member of the innate immune system, uterine natural killer (uNK) cells account for about 70% of total lymphocytes during pregnancy and play a critical role in the establishment and maintenance of pregnancy. This review mainly introduces the phenotype, origin, receptor, and function of uNK cells to illuminate its relationship with RSA.
Sulfonylurea antidiabetics are associated with lower risk of out‐of‐hospital cardiac arrest: Real‐world data from a population‐based study
Authors: Eroglu Talip E. , Jia Lixia , Blom Marieke T. , Verkerk Arie O. , Devalla Harsha D. , Boink Gerard J.J. , Souverein Patrick C. , de Boer Anthonius , Tan Hanno L.
Published: April 2021

Aims

Out‐of‐hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP‐regulated K+ channels (KATP channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes.

Methods

We conducted a population‐based case–control study in 219 VT/VF‐documented OHCA cases with diabetes and 697 non‐OHCA controls with diabetes. We studied the association of SU drugs (alone or in combination with metformin) with OHCA risk compared to metformin monotherapy, and of individual SU drugs compared to glimepiride, using multivariable logistic regression analysis. We studied the effects of these drugs on APD during simulated ischaemia using patch‐clamp studies in human induced pluripotent stem cell‐derived cardiomyocytes.

Results

Compared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (ORSUdrugs‐alone 0.6 [95% CI 0.4–0.9], ORSUdrugs + metformin 0.6 [95% CI 0.4–0.9]). We found no differences in OHCA risk between SU drug users who suffered OHCA inside or outside the context of AMI. Reduction of OHCA risk compared to glimepiride was found with gliclazide (ORadj 0.5 [95% CI 0.3–0.9]), but not glibenclamide (ORadj 1.3 [95% CI 0.6–2.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (ORadj 0.6 [95% CI 0.3–1.002]). Glibenclamide attenuated simulated ischaemia‐induced APD shortening, while the other SU drugs had no effect.

Conclusions

SU drugs were associated with reduced OHCA risk compared to metformin monotherapy, with gliclazide having a lower risk than glimepiride. The differential effects of SU drugs are not explained by differential effects on APD.
What do we know about corporate philanthropy? A review and research directions
Authors: Cha Wonsuk , Rajadhyaksha Ujvala
Published: April 2021

During the past decades, academics and practitioners have been extensively focusing on corporate philanthropy as an important part of corporate social responsibility and a vast number of papers have been published on this topic in various disciplines. To have a better understanding of the evolution of corporate philanthropy, this paper critically reviews some 60 years of research covering 228 corporate philanthropy documents (including 214 journal articles, 5 dissertations, and 9 books and book chapters) across and between disciplines, and analyzes their content in a systematic and comprehensive manner. A multi‐level and multidisciplinary theoretical framework that synthesizes and integrates the corporate philanthropy literature at micro‐, meso‐, and macro‐levels of analysis is offered. Specifically, the framework presents antecedents, intermediaries (moderators and mediators), consequences of corporate philanthropy, and the underlying mechanisms of the corporate philanthropy–firm performance relationship. This paper helps bridge important knowledge gaps of corporate philanthropy and its relation with firm performance by studying corporate philanthropy at a multi‐level of analysis and applying diverse theoretical frameworks of corporate philanthropy. The paper concludes by offering several suggestions for future research on corporate philanthropy.
When were the straits between the Baltic Sea and the Kattegat inundated by the sea during the Holocene?
Authors: Bennike Ole , Jensen Jørn Bo , Nørgaard‐Pedersen Niels , Andresen Katrine Juul , Seidenkrantz Marit‐Solveig , Moros Matthias , Wagner Bernd
Published: April 2021

The timing of the flooding of the Danish/German/Swedish straits and the first marine influence in the Baltic Basin after the Ancylus Lake stage has been much debated. Here we present 47 new radiocarbon ages from sediment cores retrieved from Danish waters, ages that record the marine transgression of the area. Most of the ages are based on shells of marine molluscs, hence the ages are uncertain because we do not know the precise reservoir age in the past. We use a reservoir age of 400 years, which is based on dating of museum specimens collected live before testing of nuclear bombs. It appears from the ages that the Great Belt (Storebælt) was inundated before The Sound (Øresund). The oldest ages on marine shells from the northern part of the Great Belt region are about 8.9 cal. ka BP. From the central part of the Great Belt, the oldest ages are about 8.2 cal. ka BP, in Mecklenburg Bay 8.1 cal. ka BP and in the Arkona Basin 7.1 cal. ka BP. Sediments deposited prior to the occurrence of marine molluscs contain brackish‐water ostracods (Cyprideis torosa and Cytheromorpha fuscata); the sediments are usually laminated and non‐bioturbated mud. The brackish‐water phase may have lasted 500–1000 years. The youngest lake deposits without signs of marine influence are dated to c. 8.8 cal. ka BP (central Great Belt), 8.7 cal. ka BP (Little Belt) and 8.5 cal. ka BP (Arkona Basin). We see no evidence for marine influence at c. 10 cal. ka BP as recorded by some studies from the Baltic Basin.
Evidence for an Early Novelty Orientation in Bilingual Learners
Authors: Singh Leher
Published: April 2021

Bilingual environments are more complex than monolingual environments. To adapt to this complexity, bilingual infants may navigate their environment in fundamentally different ways than monolingual infants. Drawing from visual, social, and linguistic processing, in this article, I present evidence to suggest that bilingual and monolingual learners demonstrate basic differences in the distribution of attention. Across these areas, bilingual learners appear to orient to novel information over familiar information, more so than monolingual learners. Attending more broadly within one’s environment may support flexibility of learning within a complex environment, where underlying structure is harder to detect. However, broad exploration may also protract the process by which underlying structure is detected and learned. This may introduce developmental costs, such as delayed specialization in the native language observed in bilingual infants. In this way, bilingual infants may explore their surroundings in a manner distinct from monolingual infants that is both responsive to and adaptive for a relatively complex environment.
Patch testing with aluminium Finn Chambers could give false‐positive reactions in patients with contact allergy to aluminium
Authors: Rosholm Comstedt Lisbeth , Dahlin Jakob , Bruze Magnus , Hedberg Yolanda , Matura Mihály , Svedman Cecilia
Published: April 2021

Background

Earlier laboratory studies have shown that sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride trigger the release of aluminium (Al) from Finn Chambers (FC).

Objectives

To investigate whether aluminium realease from FC could influence the diagnostic outcome of patch testing with FC.

Method

A retrospective analysis of patch test results from 2010 to 2019 was performed. A two‐sided Fisher's exact test was used to calculate any overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride.

Results

A total of 5446 patients had been tested with FC during the study period. There was a significant overrepresentation of contact allergy to Al among patients with positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride. Patients with a strong Al allergy had significantly higher amounts of concomitant reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride compared to patients with weak Al allergy. These results were not seen for patients tested with Finn Chambers AQUA.

Conclusion

In patients with contact allergy to Al, patch testing with Finn chambers could give false‐positive reactions to sodium tetrachloropalladate, Myroxylon pereirae, caine mix II, and palladium chloride.
Laboratory predictors of severe Coronavirus Disease 2019 and lung function in followed‐up
Authors: Pan Min , Wang Rui‐rui , Chen Xu , Han Jun , Li Qiang , Miao Manli , Rao Jianguo , Huang Jizheng , Yu Long , Xu Yufei , Li Lingli , Shao Qiang , Ma Hengli , Han Mingfeng , Fan Xiaoyun
Published: April 2021

Background

A pandemic caused by SARS‐CoV‐2 has infected more than 79 million people and killed exceeding 1.7 million people around the world by the end of 2020.

Method

We obtained the clinical data of all diagnosed patients and lung function test of followed‐up patients in Fuyang, Anhui province to investigate laboratory predictors of severe Coronavirus Disease 2019 (COVID‐19) and the impairment of lung function.

Results

Of the 155 patients, 87 (56.13%) were males. The mean age was 41.95 (SD 15.34) years. Only 30 (19.35%) patients had the critical condition. Fever (84.52%) was the most common symptoms, and short of breath was more common in severe patients (p < 0.01). Lymphopenia was observed in most patients (74, 47.7%). It showed the elevation of CRP in 100 (64.5%) patients, the elevation of SAA or IL‐6 in 104 (67.1%) patients. The calculated cut‐off value of CRP was 19.35 mg/ml, the AUC was 0.777, sensitivity was 73.3%, specificity was 69.6%; SAA was 73.55 mg/L, 0.679, 83.3%, 56.8%, respectively; IL‐6 was 18.85 pg/ml, 0.797, 83.3%, 64.8%; D‐Dimer was 0.325 mg/L, 0.673, 66.7% and 68.8%. The combination of CRP, SAA, IL‐6, and D‐Dimer was 0.823 in AUC, 73.3% in sensitivity, and 78.4% in specificity. 12 (42.86%) followed‐up patients had completely normal lung function indicators.

Conclusion

Elevated CRP, SAA, IL‐6 and D‐Dimer can be predictors to severe COVID‐19. The combination of these four indicators can improve the effectivity and specificity of assessing severe COVID‐19. Most of the followed‐up patients showed no abnormalities in lung function test. Abnormal lung function is mainly reflected in the diffusion function.
Analyzing the clinical outcomes of switching from cyclosporine to tacrolimus in pediatric hematopoietic stem cell transplantation
Authors: Yalcin Koray , Celen Suna , Zhumatayev Suleimen , Daloglu Hayriye , Pashayev Dayanat , Öztürkmen Seda , Uygun Vedat , Karasu Gulsun , Yesilipek Akif
Published: April 2021

Objective

The selection of graft‐vs. ‐host disease (GvHD) prophylaxis is vital for the success of hematopoetic stem cell transplantation (HSCT), and calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. The aim of this study is to analyze the results of switching cyclosporine (CSA) to tacrolimus because of acute GvHD, engraftment syndrome (ES), persistent low level of CSA, or various CSA‐associated adverse events in the first 100 days of pediatric HSCT.

Materials and Methods

This is a retrospective analysis of 192 patients who underwent allogeneic hematopoietic stem cell transplantation at Medicalpark Göztepe and Antalya Hospitals between April 2014 and May 2019 had therapy switched from CSA to tacrolimus‐based immunosuppression within 100 days of transplant.

Results

The reasons for conversion to tacrolimus were low level of CSA (n = 70), aGvHD (n = 63), CSA‐associated neurotoxicity (n = 15), CSA‐associated nephrotoxicity (n = 10), hypertension (n = 10), allergic reactions (n = 9), ES (n = 7), CSA‐associated hepatotoxicity (n = 5), and vomiting (n = 3). The median day after transplant for conversion to tacrolimus for all patients was day 20 (range 0‐100 days). Response rates to conversion were 38% for GvHD, 86% for neurotoxicity, 50% for nephrotoxicity, 60% for hepatotoxicity, 80% for hypertension, 66% for vomiting, and 57% for ES. Twenty‐nine patients (15%) experienced tacrolimus‐associated toxicities after therapy conversion to tacrolimus. Neurotoxicity emerged as posterior reversible encephalopathy syndrome (PRES), which was the most common toxicity observed after conversion (18/29 patients).

Conclusion

Our data support the quick conversion to tacrolimus in the condition of persistent low CSA levels with acceptable efficacy and safety. Although both drugs are CNI and share a very similar mechanism of action, the conversion could be preferred especially in specific organ toxicities with special attention for neurotoxicity after conversion.
Damping‐off, root rot and wilting caused by Pythium myriotylum on Acacia crassicarpa in Sumatra, Indonesia
Authors: Oliveira Leonardo Sarno Soares , Jung Thomas , Milenković Ivan , Tarigan Marthin , Horta Jung Marília , Lumbangaol Pantun David Mangatas , Sirait Betti Andriany , Durán Álvaro
Published: April 2021

Acacia crassicarpa is a legume tree of rapid growth and high pulp yield and fibre quality, making this species the basis of large commercial plantations for pulpwood production in Southeast Asian countries. Since a disease has caused significant economic losses in a nursery in the province of Riau, Sumatra, Indonesia, this study aimed to identify the causal agent of the root rot, damping‐off and wilting symptoms of A. crasicarpa seedlings. Isolations were made from infested soil by baiting with young leaves of native Quercus spp. from northern Sumatra. Classical identification using colony growth patterns and morphological characters, molecular identification based on ITS sequence analysis and direct PCR with specific primers, and pathogenicity tests were performed. All isolates formed typical Pythium structures and had fast growth, with optimum and maximum temperatures of 35 and 42°C, respectively. ITS sequence analysis of seven selected isolates showed 99.7–99.9% homology with Pythium myriotylum, the causal agent of nursery diseases on many crops. In addition, species‐specific primers Pmy5/ITS2 successfully yielded an expected amplicon of approximately 144 bp. A soil infestation trial under controlled conditions confirmed the pathogenicity of P. myriotylum to A. crassicarpa, with typical symptoms starting six days after inoculation. The pathogen was re‐isolated only from diseased inoculated plants fulfilling Koch's postulates. This is the first report of P. myriotylum as a pathogen on A. crassicarpa.
Brain‐specific functions of the endocytic machinery
Authors: Camblor‐Perujo Santiago , Kononenko Natalia L.
Published: April 2021

Endocytosis is an essential cellular process required for multiple physiological functions, including communication with the extracellular environment, nutrient uptake, and signaling by the cell surface receptors. In a broad sense, endocytosis is accomplished through either constitutive or ligand‐induced invagination of the plasma membrane, which results in the formation of the plasma membrane‐retrieved endocytic vesicles, which can either be sent for degradation to the lysosomes or recycled back to the PM. This additional function of endocytosis in membrane retrieval has been adopted by excitable cells, such as neurons, for membrane equilibrium maintenance at synapses. The last two decades were especially productive with respect to the identification of brain‐specific functions of the endocytic machinery, which additionally include but not limited to regulation of neuronal differentiation and migration, maintenance of neuron morphology and synaptic plasticity, and prevention of neurotoxic aggregates spreading. In this review, we highlight the current knowledge of brain‐specific functions of endocytic machinery with a specific focus on three brain cell types, neuronal progenitor cells, neurons, and glial cells.
Inhibition of receptor‐interacting protein kinase‐3 in the necroptosis pathway attenuates inflammatory bone loss in experimental apical periodontitis in Balb/c mice
Authors: Liu Jie , Wang Jiajia , Ren Jie , Yang Qin , Zhan Weicheng , Wang Min , Hao Liang , Yue Yuan
Published: April 2021

Aim

To explore the role of necroptosis in apical periodontitis (AP), this study investigated necroptosis in a Fusobacterium nucleatum (Fn)‐induced AP model of Balb/c mice and explored related intracellular signalling pathways in L929 cells affected by Fn.

Methodology

For the in vivo experiments, expression of receptor‐interacting protein kinase‐3 (RIP3) was inhibited using an adeno‐associated virus and then the Balb/c mice model of AP was established by injecting Fn into the root canal of the first mandibular molars. Bone loss and number of osteoclasts were measured via micro‐computed tomography and tartrate‐resistant acid phosphatase staining, respectively; expression of RIP3 and phosphorylated mixed lineage kinase domain‐like protein (pMLKL) was detected by immunohistochemistry and western blotting; expression of mRNA of inflammatory cytokines was evaluated using quantitative real‐time polymerase chain reaction (qRT‐PCR). For the in vitro experiments, L929 cells transfected with RIP3‐Mus‐siRNA or negative control siRNA were co‐cultured with Fn; thereafter, western blotting, detection of cell death and viability and qRT‐PCR analyses were performed to assess the activation of necroptosis pathway and expression of mRNA of inflammatory cytokines. Data were analysed with unpaired t‐test and one‐way analysis of variance with significance set at p < .05.

Results

The Fn‐induced apical lesions were associated with apical bone loss, an increased number of osteoclasts, enhanced expression of pMLKL and increased mRNA levels of inflammatory cytokines(IL‐1α and IL‐1β); all these effects were alleviated by RIP3 inhibition (p < .05). L929 cells infected with Fn displayed increased expression of pMLKL and increased cell death (p < .05), together with decreased cell viability (p < .05), whilst transfection with RIP3‐Mus‐siRNA decreased the mRNA expression of inflammatory cytokines(TNF‐α and IL‐6, p < .05).

Conclusions

Necroptosis may be involved in AP progression. RIP3 inhibition ameliorated the expression of inflammatory cytokines and bone resorption in Fn‐induced AP lesions in Balb/c mice.
The impact of lesional inflammatory cellular infiltrate on the phenotype of bullous pemphigoid
Authors: Ständer S. , Hammers C.M. , Vorobyev A. , Schmidt E. , Zillikens D. , Ghorbanalipoor S. , Bieber K. , Ludwig R.J. , Kridin K.
Published: April 2021

Background

The influence of cutaneous cellular infiltration on the phenotype of bullous pemphigoid (BP) remains to be established.

Objectives

To evaluate the main histopathological characteristics of patients with BP and to assess the association between the composition of lesional inflammatory infiltrate and the various clinical, immunological and immunopathological aspects of the disease.

Methods

Retrospective study encompassing patients diagnosed with BP throughout the years 2009–2020 in a specialized tertiary referral centre.

Results

The study encompassed 136 patients with BP, of whom 27 (19.9%) demonstrated a cell‐poor inflammatory infiltrate in lesional skin specimens. Overall, 78 (57.4%), 71 (52.2%) and 5 (3.7%) specimens were found to include eosinophil‐predominant, lymphocyte‐predominant and neutrophil‐predominant inflammatory infiltrates, respectively. Relative to the remaining patients with BP, those with an eosinophil‐predominant inflammatory infiltrate had higher (90.8% vs. 77.2%; P = 0.030) whilst those with a cell‐poor inflammatory infiltrate lower (70.3% vs. 88.7%; P = 0.017) seropositivity of anti‐BP180 NC16A IgG. The latter subgroup presented with higher prevalence of mucosal involvement (25.9% vs. 8.3%; P = 0.011) and a non‐inflammatory clinical phenotype (50.0% vs. 17.1%; P = 0.041). Patients with lymphocyte‐predominant inflammatory infiltrate manifested with higher severity BPDAI scores and a lower frequency of the non‐inflammatory subtype (11.1% vs. 36.4%; P = 0.035), whilst those with a neutrophilic infiltrate presented with lower mean (SD) levels of anti‐BP180 NC16A IgG [269.3 (227.6) vs. 722.7 (1499.6) U/mL; P = 0.003].

Conclusions

Eosinophil‐predominance and high cellularity in the lesional inflammatory infiltrate of BP skin are associated with increased seropositivity of anti‐BP180 NC16A IgG. Lymphocyte‐predominant infiltrates predict a more severe phenotype, pointing towards a pathogenic role of autoreactive lymphocytes.
Capital‐based life cycle sustainability assessment: Evaluation of potential industrial symbiosis synergies
Authors: Subramanian Karpagam , Chopra Shauhrat S. , Ashton Weslynne S.
Published: April 2021

Industrial symbiosis (IS) promotes collaboration among traditionally unrelated industries, finding ways to use waste from one as a raw material for another. To enhance IS sustainability, it is essential that involved firms are aware of potential costs and benefits of new exchanges to make informed decisions. Previous assessments have primarily focused on environmental and financial implications of potenial IS synergies, but social implications are rarely addressed. Even when considered, only a limited set of social indicators, such as job creation, development of social ties, and trust among partners, are used. Such an unbalanced focus on sustainability aspects may contribute to problem shifting and suboptimal selection of new synergies. A comprehensive life cycle sustainability assessment (LCSA) of IS, covering all three dimensions is clearly lacking. Conventionally, a triple bottom line (TBL) approach is used to evaluate sustainability; however, we explore the concept of capitals and develop a capital‐based LCSA framework as a means to evaluate sustainability of IS by examining the stocks and flows of eight different types of capital, or resources creating value, in a system. Measuring stocks and flows is conceptually much closer to the actual definition of sustainability (meeting the needs of the present by maintaining the available stocks without compromising the future needs), when compared to the TBL approach of simply aggregating environmental, social, and economic impact assessment results. This novel LCSA approach is tested at a facility with active IS, The Plant in Chicago, considering three alternative fuel usage scenarios for baking bread at an on‐site bakery.
Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice
Authors: Nair Betina B. , Khant Aung Zin , Porteous Robert , Prescott Melanie , Glendining Kelly A. , Jenkins Danielle E. , Augustine Rachael A. , Silva Mauro S.B. , Yip Siew H. , Bouwer Gregory T. , Brown Colin H. , Jasoni Christine L. , Campbell Rebecca E. , Bunn Stephen J. , Anderson Greg M. , Grattan David R. , Herbison Allan E. , Iremonger Karl J.
Published: April 2021

Chronic stress exerts multiple negative effects on the physiology and health of an individual. In the present study, we examined hypothalamic, pituitary and endocrine responses to 14 days of chronic variable stress (CVS) in male and female C57BL/6J mice. In both sexes, CVS induced a significant decrease in body weight and enhanced the acute corticosterone stress response, which was accompanied by a reduction in thymus weight only in females. However, single‐point blood measurements of basal prolactin, thyroid‐stimulating hormone, luteinising hormone, growth hormone and corticosterone levels taken at the end of the CVS were not different from those of controls. Similarly, pituitary mRNA expression of Fshb, Lhb, Prl and Gh was unchanged by CVS, although Pomc and Tsh were significantly elevated. Within the adrenal medulla, mRNA for Th, Vip and Gal were elevated following CVS. Avp transcript levels within the paraventricular nucleus of the hypothalamus were increased by CVS; however, levels of Gnrh1, Crh, Oxt, Sst, Trh, Ghrh, Th and Kiss1 remained unchanged. Oestrous cycles were lengthened slightly by CVS and ovarian histology revealed a reduction in the number of preovulatory follicles and corpora lutea. Taken together, these observations indicate that 14 days of CVS induces an up‐regulation of the neuroendocrine stress axis and creates a mild disruption of female reproductive function. However, the lack of changes in other neuroendocrine axes controlling anterior and posterior pituitary secretion suggest that most neuroendocrine axes are relatively resilient to CVS.
Ontogenetic development of the holocephalan dentition: Morphological transitions of dentine in the absence of teeth
Authors: Johanson Zerina , Manzanares Esther , Underwood Charlie , Clark Brett , Fernandez Vincent , Smith Moya
Published: April 2021

Among the cartilaginous fishes (Chondrichthyes), the Holocephali are unique in that teeth are absent both in ontogeny and adult regenerative growth. Instead, the holocephalan dentition of ever‐growing nonshedding dental plates is composed of dentine, trabecular in arrangement, forming spaces into which a novel hypermineralized dentine (whitlockin) is deposited. These tissue features form a variety of specific morphologies as the defining characters of dental plates in the three families of extant holocephalans. We demonstrate how this morphology changes through ontogenetic development with continuity between morphologies, through successive growth stages of the dentition represented by the dental plate. For example, rod‐shaped whitlockin appears early, later transformed into the tritoral pad, including a regular arrangement of vascular canals and whitlockin forming with increasing mineralization (95%–98%). While the tritoral pads develop lingually, stacks of individual ovoids of whitlockin replace the rods in the more labial parts of the plate, again shaped by the forming trabecular dentine. The ability to make dentine into new, distinctive patterns is retained in the evolution of the Holocephali, despite the lack of teeth forming in development of the dentition. We propose that developmentally, odontogenic stem cells, retained through evolution, control the trabecular dentine formation within the dental plate, and transition to form whitlockin, throughout lifetime growth. Our model of cellular activity proposes a tight membrane of odontoblasts, having transformed to whitloblasts, that can control active influx of minerals to the rapidly mineralizing dentine, forming whitlockin. After the reduced whitloblast cells transition back to odontoblasts, they continue to monitor the levels of minerals (calcium, phosphate and magnesium) and at a slower rate of growth in the peritubate ‘softer’ dentine. This model explains the unique features of transitions within the holocephalan dental plate morphology.
Palpation of the lateral bands of the extensor apparatus of the fingers. Anatomy of a neglected clinical finding
Authors: Canoso Juan J. , Naredo Esperanza , Martínez‐Estupiñán Lina , Mérida‐Velasco José Ramón , Pascual‐Ramos Virginia , Murillo‐González Jorge
Published: April 2021

This study aimed to determine by ultrasonography, and cadaveric dissection, whether the firm cords felt by palpation at the sides of the proximal phalanx (PP), actively flexing, and extending the proximal interphalangeal (PIP) joint while keeping the metacarpophalangeal (MCP) joint extended are the lateral bands (LBs) of the extensor apparatus. If so, palpation of the LBs could help evaluate hand conditions that impact the digits’ intrinsic muscles. To this end, the PP of the middle and ring fingers of the dominant hand of seven subjects were studied by palpation on both sides. Ultrasonography (US) was performed with a hockey‐stick transducer placed on the ulnar side. Five cadaveric hands were dissected, exposing the dorsal extensor apparatus. On palpation, a firm cord was consistently felt at the PP's sides in all subjects. These cords moved widely forward on PIP flexion and backward with PIP extension. By US scanning, the cords corresponded to the LBs. However, the forward movement had only a median of 1.8 mm (range 0.7–3 mm) in the middle finger and a median of 1.1 mm (range 0.3–2.7 mm) in the ring finger compared with an estimated 5–10 mm upon palpation. Cadaveric dissection confirmed the forward movement of the LBs in PIP flexion. We concluded that the firm cords felt at the PP sides are the LBs of the extensor apparatus. We confirmed their movement with the active flexion/extension of the PIP joint. Comparing the wide palpatory and the meager US motion, a haptic illusion of motion may be present.
Cognitive and social strengths of people living with dementia: Discoveries through Harré’s method
Authors: Sabat Steven R.
Published: April 2021

From the time Alzheimer’s disease (AD) was described and named in the first decades of the 20thCentury, a biomedical lens was used to examine and understand what Oliver Sacks 1970) called ‘the disease the person has’ and the dysfunctions caused by that disease. Treatments were mainly pharmaceutical and neuropsychological tests administered in clinics were among the outcome measures used to quantify dysfunctions and assess the efficacy of drugs. The final decades of the 20thCentury and the first decades of the 21stCentury witnessed the advent of qualitative approaches to understanding what Sacks termed, ‘the person the disease has’. The theoretical contributions of Rom Harré were essential to the identification of important aspects of the subjective experience and selfhood, as well as significant cognitive and social strengths, possessed by people deemed to be in the moderate to severe stages of the disease. I shall explore some of those contributions and their significance herein.