bluuebunny/crossref_metadata_2025 huggingface dataset:
Do cooperatively breeding mammals live longer? A re-appraisal
Authors: Thorley Jack
Published: September 2019

Recent comparative studies have suggested that cooperative breeding is associated with increases in maximum lifespan among mammals, replicating a pattern also seen in birds and insects. In this study, I re-examine the case for increased lifespan in mammalian cooperative breeders by analysing a large dataset of maximum longevity records. Unlike one previous study, I found no consistent, strong evidence that cooperative breeders have longer lifespans than other mammals, after having controlled for variation in body mass, mode of life and data quality. The only exception to this general trend was displayed by the African mole-rats (the Bathyergid family): all members of this family are relatively long-lived, but the social, cooperatively breeding species appear to be much longer-lived than the solitary species, the latter having not been known to live beyond 11 years in captivity. However, solitary mole-rat species have rarely been kept in captivity or followed longitudinally in the wild, and so it seems likely that their maximum lifespan has been grossly underestimated when compared to the highly researched social species. As few other subterranean species have received much attention in a captive or wild setting, I also suggest that current data also makes it impossible to rule out a causal role of subterranean living on lifespan extension in mammals, and that any future studies wanting to test for such an association should wait until more high quality longevity data is available from a wider range of permanently subterranean species.
Remodeling of the H3 nucleosomal landscape during mouse aging
Authors: Chen Yilin , Bravo Juan I. , Benayoun Bérénice A.
Published: September 2019

In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin: cellular chromatin states (i.e. the ‘epigenome’) can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, though alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mice tissues (i.e. heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs with aging.
Characterization of OA development between sexes in the rat medial meniscal transection model
Authors: Pucha Krishna A. , McKinney Jay M. , Fuller Julia M. , Willett Nick J.
Published: September 2019

Objective

Osteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While there are clear sex differences in OA development in humans, most pre-clinical research has been conducted solely in male animals thus limiting the ability of these findings to be generalized to both sexes in the context of this disease. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical animal model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery.

Design

A MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure.

Results

Quantitative analysis of the medial 1/3 articular cartilage via EPIC-μCT showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Additionally, both male and female animals in the MMT group had increased subchondral bone mineral density and larger total osteophyte volumes due to MMT.

Conclusion

These data demonstrate that OA can be induced in both sexes using the rat MMT model. Moving forward, adding sex as a factor in preclinical OA studies should be standard practice in pre-clinical studies in order to elucidate more inclusive and translatable results into the clinic.
Mosquito species and age influence thermal performance of traits relevant to malaria transmission
Authors: Miazgowicz KL , Mordecai EA , Ryan SJ , Hall RJ , Owen J , Adanlawo T , Balaji K , Murdock CC
Published: September 2019

Models predicting disease transmission are a vital tool in the control of mosquito populations and malaria reduction as they can target intervention efforts. We compared the performance of temperature-dependent transmission models when mosquito life history traits were allowed to change across the lifespan of Anopheles stephensi, the urban malaria mosquito, to models parameterized with commonly derived estimates of lifetime trait values. We conducted an experiment on adult female An. stephensi to generate daily per capita values for lifespan, egg production, and biting rate at six constant temperatures. Both temperature and age significantly affected trait values. Further, we found quantitative and qualitative differences between temperature-trait relationships estimated based on daily rates versus directly observed lifetime values. Incorporating these temperature-trait relationships into an expression governing transmission suitability, relative R0(T), model resulted in minor differences in the breadth of suitable temperatures for Plasmodium falciparum transmission between the two models constructed from only An. stephensi trait data, but a substantial increase in breadth compared to a previously published model consisting of trait data from multiple mosquito species. Overall this work highlights the importance of considering how mosquito trait values vary with mosquito age and mosquito species when generating temperature-based environmental suitability predictions of transmission.
Proteostasis and Energetics as Proteome Hallmarks of Aging and Influenza Challenge in Pulmonary Disease
Authors: Loguercio Salvatore , Hutt Darren M. , Campos Alexandre Rosa , Stoeger Thomas , Grant Rogan A. , McQuattie-Pimentel Alexandra C , Abdala-Valencia Hiam , Lu Ziyan , Joshi Nikita , Ridge Karen , Chandel Navdeep S , Sznajder Jacob I. , Morimoto Richard I , Misharin Alexander V. , Budinger G.R. Scott , Balch William E.
Published: September 2019

Aging is associated with an increased risk for the development of many diseases. This is exemplified by the increased incidence of lung injury, muscle dysfunction and cognitive impairment in the elderly following influenza infection. Because the infectious cycle of flu is dependent upon the properties of the host, we examined the proteome ofalveolarmacrophages (AM) and type 2 cells (AT2) obtained from young (3 months) and old (18 months) naïve mice and mice exposed to influenza A. Our proteomics data show that there is a maladaptive collapse of the proteostasis network (PN) and changes in mitochondrial pathways in the aged naïve AM and AT2 proteomes. The mitochondrial imbalance and proteostatic collapse seen in aged cells places an excessive folding burden on these cells, which is further exacerbated following exposure to influenza A. Specifically, we see an imbalance in Hsp70 co-chaperones involved in protein folding and Hsp90 co-chaperones important for stress signaling pathways that are essential for cellular protection during aging. The acute challenge of influenza A infection of young and aged AM and AT2 cells reveals that age-associated changes in the chaperome affect the ability of these cells to properly manage the infection and post-infection biology, contributing to cytotoxicity. We posit that proteomic profiling of individual cell type specific responses provides a high impact approach to pinpoint fundamental molecular relationships that may contribute to the susceptibility to aging and environmental stress, providing a platform to identify new targets for therapeutic intervention to improve resiliency in the elderly.
Evolutionary dynamics of the SKN-1 → MED → END-1,3 regulatory gene cascade inCaenorhabditisendoderm specification
Authors: Maduro Morris F.
Published: September 2019

Gene regulatory networks (GRNs) with GATA factors are important in animal development, and evolution of such networks is an important problem in the field. In the nematode,Caenorhabditis elegans, the endoderm (gut) is generated from a single embryonic precursor, E. The gut is specified by an essential cascade of transcription factors in a GRN, with the maternal factor SKN-1 at the top, activating expression of the redundantmed-1,2divergent GATA factor genes, with the combination of all three contributing to activation of the paralogousend-3andend-1canonical GATA factor genes. In turn, these factors activate the GATA factors geneselt-2andelt-7to regulate intestinal fate. In this work, genome sequences from over two dozen species within theCaenorhabditisgenus are used to identify putative orthologous genes encoding the MED and END-1,3 factors. The predictions are validated by comparison of gene structure, protein conservation, and putativecis-regulatory sites. The results show that all three factors occur together, but only within the Elegans supergroup of related species. While all three factors share similar DNA-binding domains, the MED factors are the most diverse as a group and exhibit unexpectedly high gene amplifications, while the END-1 orthologs are highly conserved and share additional extended regions of conservation not found in the other GATA factors. The MEME algorithm identified both known and previously unrecognizedcis-regulatory motifs. The results suggest that all three genes originated at the base of the Elegans supergroup and became fixed as an essential embryonic gene regulatory network with several conserved features, although each of the three factors is under different evolutionary constraints. Based on the results, a model for the origin and evolution of the network is proposed. The set of identified MED, END-3 and END-1 factors form a robust set of factors defining an essential embryonic gene network that has been conserved for tens of millions of years, that will serve as a basis for future studies of GRN evolution.
Aggregatibacter actinomycetemcomitansLtxA hijacks endocytic trafficking pathways in human lymphocytes
Authors: Lally Edward T , Boesze-Battaglia Kathleen , Dhingra Anuradha , Gomez Nestor M , Mitchell Claire H , Giannakakis Alexander , Fahim Syed A , Benz Roland , Balashova Nataliya
Published: September 2019

Leukotoxin (LtxA) from oral pathogenAggregatibacter actinomycetemcomitansis a secreted membrane-damaging protein. LtxA is internalized by β2 integrin LFA-1 (CD11a/CD18) expressing leukocytes and ultimately causes cell death; however toxin localization in the host cell is poorly understood and these studies fill this void. We investigated LtxA trafficking using multi-fluor confocal imaging, flow cytometry and Rab5 knockdown in human T lymphocyte Jurkat cells. Planar lipid bilayers were used to characterize LtxA pore-forming activity at different pH. Our results demonstrate that LtxA/LFA-1 complex gains an access to the cytosol of Jurkat cells without evidence of plasma membrane damage utilizing dynamin-dependent and clathrin-independent mechanism. Upon internalization LtxA follows the LFA-1 endocytic trafficking pathways as identified by co-localization experiments with endosomal and lysosomal markers (Rab5, Rab11A, Rab7, and Lamp2) and CD11a. Knockdown of Rab5a resulted in loss of susceptibility of Jurkat cells to LtxA cytotoxicity suggesting that late events of LtxA endocytic trafficking are required for toxicity. The toxin trafficking via the degradation endocytic pathway may culminate in delivery of the protein to lysosomes or its accumulation in Rab11A-dependent recycling endosomes. The ability of LtxA to form pores at acidic pH may result in permeabilization of the endosomal and lysosomal membranes.
De Novo Protein Design for Novel Folds using Guided Conditional Wasserstein Generative Adversarial Networks (gcWGAN)
Authors: Karimi Mostafa , Zhu Shaowen , Cao Yue , Shen Yang
Published: September 2019

Motivation

Facing data quickly accumulating on protein sequence and structure, this study is addressing the following question: to what extent could current data alone reveal deep insights into the sequence-structure relationship, such that new sequences can be designed accordingly for novel structure folds?

Results

We have developed novel deep generative models, constructed low-dimensional and generalizable representation of fold space, exploited sequence data with and without paired structures, and developed ultra-fast fold predictor as an oracle providing feedback. The resulting semi-supervised gcWGAN is assessed with the oracle over 100 novel folds not in the training set and found to generate more yields and cover 3.6 times more target folds compared to a competing data-driven method (cVAE). Assessed with structure predictor over representative novel folds (including one not even part of basis folds), gcWGAN designs are found to have comparable or better fold accuracy yet much more sequence diversity and novelty than cVAE. gcWGAN explores uncharted sequence space to design proteins by learning from current sequence-structure data. The ultra fast data-driven model can be a powerful addition to principle-driven design methods through generating seed designs or tailoring sequence space.

Availability

Data and source codes will be available upon request.

Contact

yshen@tamu.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Sex Lability and Dimorphism in Dioecious Palmer Amaranth (Amaranthus palmeri)
Authors: Mesgaran Mohsen B. , Matzrafi Maor , Ohadi Sara
Published: September 2019

Dioecious weeds (separate sexes) may benefit from a maximized outcrossing and optimal sex-specific resource allocation but there are costs associated with the evolution of this breeding system which can be exploited for long-term management of dioecious weeds. That is, seed production in dioecious species is contingent upon the co-occurrence and co-flowering of the two genders and can be further complicated by biases in sex ratio. We therefore explored the sex ratio and dimorphism in secondary sex characters in three populations of Palmer amaranth (Amaranthus palmeri) from California, Kansas and Texas and tested if water stress can change the sex expression and/or the synchrony of flowering (anthesis) between male and female plants. Sex ratio (proportion of males) was balanced and did not deviate from 1:1 in all experiments and populations (California, Kansas, Texas) when plants received normal watering. Male and female plants of A. palmeri did not differ in timing of emergence, plant height and relative growth rate. While the initiation of flowering (emergence of inflorescence) occurred earlier in males than females, females preceded males in timing of anthesis. Water stress delayed anthesis in males to a larger extent than females giving rise to an anthesis mismatch as large as seven days between the two sexes. Water stress induced a female sex expression in Kansas population giving rise to a female to male ratio of 1.78 which significantly differed from the equal 1:1 sex ratio. Our data provide the first evidence of sex lability and environment sex determination (ESD) in A. palmeri, suggesting manipulation of sex expression and phenological asynchrony as novel tools for ecological management of dioecious weeds.
Look‐ahead vertical seismic profiling inversion approach for density and compressional wave velocity in Bayesian framework
Authors: Daoud Ahmed M. , Abd El Dayem Muhammad A.
Published: September 2019

To reduce drilling uncertainties, zero‐offset vertical seismic profiles can be inverted to quantify acoustic properties ahead of the bit. In this work, we propose an approach to invert vertical seismic profile corridor stacks in Bayesian framework for look‐ahead prediction. The implemented approach helps to successfully predict density and compressional wave velocity using prior knowledge from drilled interval. Hence, this information can be used to monitor reservoir depth as well as quantifying high‐pressure zones, which enables taking the correct decision during drilling. The inversion algorithm uses Gauss–Newton as an optimization tool, which requires the calculation of the sensitivity matrix of trace samples with respect to model parameters. Gauss–Newton has quadratic rate of convergence, which can speed up the inversion process. Moreover, geo‐statistical analysis has been used to efficiently utilize prior information supplied to the inversion process. The algorithm has been tested on synthetic and field cases. For the field case, a zero‐offset vertical seismic profile data taken from an offshore well were used as input to the inversion algorithm. Well logs acquired after drilling the prediction section was used to validate the inversion results. The results from the synthetic case applications were encouraging to accurately predict compressional wave velocity and density from just a constant prior model. The field case application shows the strength of our proposed approach in inverting vertical seismic profile data to obtain density and compressional wave velocity ahead of a bit with reasonable accuracy. Unlike the commonly used vertical seismic profile inversion approach for acoustic impedance using simple error to represent the prior covariance matrix, this work shows the importance of inverting for both density and compressional wave velocity using geo‐statistical knowledge of density and compressional wave velocity from the drilled section to quantify the prior covariance matrix required during Bayesian inversion.
Draper, the “Conflict Thesis” and Secularising Politics in Late Nineteenth‐Century Argentina
Authors: de Asúa Miguel
Published: September 2019

Despite appearances to the contrary, late nineteenth‐century Buenos Aires (Argentina) seems to be a suitable scale model to explore the relationships between the “conflict thesis” and secularisation. John W. Draper's History of the Conflict between Religion and Science (1874) arrived in the country in the midst of political battles over the shape of the future relationships between the state and the majoritarian Catholic Church. In the decade between 1875 and 1885 variants of the “conflict thesis” were expounded, discussed, and used as rhetorical weapons in the battles over the issue of religious teaching in elementary schools. This article analyses the discussions over the “conflict thesis” between liberal secularists and Catholics in newspaper articles, public speeches, parliamentary debates, and other forms of public discourse during that period. Against the backdrop of a weak institutional church, a vigorous growth of nascent scientific institutions, and a cultural atmosphere permeated by positivism, the opposing parties argued about the “conflict thesis” while each reclaimed for itself the legitimacy of science. The episode permits a close look at how the intellectual leaders who conceived the project of a secularised state utilised science‐based philosophies for purposes of political argument and ideological legitimation.
Radiation dose and risk to the lens of the eye during CT examinations of the brain
Authors: Poon Rebekah , Badawy Mohamed K
Published: September 2019

Cataracts are the leading cause of blindness and visual disability worldwide. Of the known contributing factors to this condition, ionising radiation is considered the primary concern in a radiological context given the particular radiosensitivity of the lens of the eye. In light of the substantially increased application of computed tomography in brain imaging, an investigation of the relevent literature is warranted to assess thresholds, lens radiation doses and dose reduction techniques in respect to the cataractogenic risk of such examinations. The value and very existence of a lens dose threshold is debatable given different considerations of radiation dose, latency, opacity classifications and historical sample populations, though ICRP guidelines suggest a threshold of 0.5 Gy. Documented CT‐specific radiation doses to the eye following scans of the brain are highly variable between studies (2–130 mGy), primarily owing to discrepancies in scanning technique. These findings, when coupled with the relative ambiguity of known threshold values, present difficulties in assessing the overall risk of cataracts following serial CT examinations to the head. In the absence of definitive risk evaluations, a cautionary approach is advised. The implementation of gantry tilt along the supraorbital margin is recommended as standard practice on account of its highly effective radiation dose reduction outcomes. Organ‐based tube modulation and reductions in tube current may also be considered beneficial. Bismuth eye shielding is only advised where gantry tilting is unachievable, and in such cases, ensure careful adherence to appropriate shield placement and infection control measures.
Monitoring antibody binding to T cells in a pembrolizumab‐treated patient with lung adenocarcinoma on hemodialysis
Authors: Osa Akio , Uenami Takeshi , Naito Yujiro , Hirata Haruhiko , Koyama Shohei , Takimoto Takayuki , Shiroyama Takayuki , Futami Shinji , Nakatsubo Saeko , Sawa Nobuhiko , Yano Yukihiro , Nagatomo Izumi , Takeda Yoshito , Mori Masahide , Kida Hiroshi , Kumanogoh Atsushi
Published: September 2019

Recent clinical trials have demonstrated that anti‐PD‐1 blocking antibodies showed remarkable clinical efficacy in a subset of non‐small cell lung cancer (NSCLC) patients. Clinical trials usually exclude patients with renal dysfunction who are receiving hemodialysis (HD). Therefore, it is unclear whether these patients can be safely and effectively treated with pembrolizumab. Here, we present a non‐small cell lung cancer patient on HD who achieved complete remission after one dose of pembrolizumab without severe adverse events. We assessed pembrolizumab binding to peripheral blood T cells in this patient using a method that we recently developed. This is the first report to visualize pembrolizumab binding to T cells in a patient on HD during and after pembrolizumab treatment. The pharmacokinetics of pembrolizumab in this case were similar to those in patients with normal renal function, suggesting that severe renal dysfunction has little influence on the metabolism of pembrolizumab, and is not a contraindication for anti‐PD‐1 treatment. Immune checkpoint inhibitors, including pembrolizumab, may be a vital therapeutic option for lung cancer patients on HD.
EAACI position paper on diet diversity in pregnancy, infancy and childhood: Novel concepts and implications for studies in allergy and asthma
Authors: Venter Carina , Greenhawt Matthew , Meyer Rosan W. , Agostoni Carlo , Reese Imke , du Toit George , Feeney Mary , Maslin Kate , Nwaru Bright I. , Roduit Caroline , Untersmayr Eva , Vlieg‐Boerstra Berber , Pali‐Schöll Isabella , Roberts Graham C. , Smith Peter , Akdis Cezmi A. , Agache Ioana , Ben‐Adallah Miriam , Bischoff Stephan , Frei Remo , Garn Holger , Grimshaw Kate , Hoffmann‐Sommergruber Karin , Lunjani Nonhlanhla , Muraro Antonella , Poulsen Lars K. , Renz Harald , Sokolowska Milena , Stanton Catherine , O'Mahony Liam
Published: September 2019

To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.
Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study
Authors: Gravesteijn B. Y. , Sewalt C. A. , Ercole A. , Lecky F. , Menon D. , Steyerberg E. W. , Maas A. I. R. , Lingsma H. F. , Klimek M. ,   the CENTER‐TBI collaborators
Published: September 2019

Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER‐TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed‐effects multinomial regression to quantify the effects on pre‐hospital or in‐hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre‐hospital and 483 (13%) in‐hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre‐hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1–4.3) for pre‐hospital intubation, and 2.7 (95%CI 1.9–3.5) for in‐hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre‐hospital intubation (OR 2.9, 95%CI 1.3–6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3–0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between‐centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.
Balancing values and obligations when obtaining informed consent: Healthcare professionals' experiences in Swedish paediatric oncology
Authors: Schröder Håkansson Anna , Pergert Pernilla , Abrahamsson Jonas , Stenmarker Margaretha
Published: September 2019

Aim

To explore Swedish healthcare professionals’ (HCPs) clinical experiences of the informed consent process (ICP) and to compare experiences between the professions.

Methods

In this nationwide study six paediatric oncologists (POs) and eight research nurses (ReNs) from all Swedish paediatric oncology centres were interviewed. The material was analysed using Grounded theory, a qualitative constant comparative method.

Results

The participants’ main concern was how to fulfil research obligations without putting too much strain on a family in acute crisis, which led to the core category of balancing values and obligations of both healthcare and research. To handle the challenges the participants’ struggled to safeguard the families from psychological harm, tried to adjust to the families, and gradually introduced research while building trust. The conceptual model developed in the study highlights potential consequences of this balancing act with a risk of diminishing the family's autonomy through HCPs acting authoritatively (in particular POs) or with overprotection (in particular ReNs).

Conclusion

Paediatric oncology is a research integrated healthcare environment. The HCPs need personal, professional and institutional support regarding ICP‐related ethical issues, decisions and implications in this intertwined context. Furthermore, HCPs need to be aware of the potential long‐term risk of developing professional moral distress.
Correlation of registered drug packs with Maastricht V/Florence Consensus Report and national treatment guidelines for management of Helicobacter pylori infection
Authors: Jukic Ivana , Rusic Doris , Vukovic Jonatan , Zivkovic Piero Marin , Bukic Josipa , Leskur Dario , Seselja Perisin Ana , Luksic Marko , Modun Darko
Published: September 2019

High prevalence of Helicobacter pylori infection, the complexity for its treatment, poor correlation of registered drug packs or poor patient adherence to the treatment may contribute to antibiotic resistance and healthcare costs. The aim of the present study was to investigate whether registered drug packs are in accordance with European and national guidelines for H pylori eradication with reference to the number of drug units. In this study, we considered treatment options for the management of H pylori infection recommended by the Maastricht V/Florence Consensus Report and by national guidelines in the United Kingdom (UK), Croatia, Italy and Slovenia for adults. Drugs proposed by the guidelines were identified in national drug databases in July of 2019. When considering correlation for 10‐day treatment regimens, drug packs registered in Croatia could not be matched with recommendations for sequential therapies. A number of proposed treatments could not be matched due to small variety of drug packs in Croatia. Drug packs registered in the UK more often matched recommended 14‐day treatment regimens and national guidelines. With reference to European guidelines, 10‐day treatments could more frequently be matched in Italy and in Slovenia. Furthermore, results of this study indicate that there is smaller variety in drug pack sizes registered in Croatia and Slovenia when compared to UK and Italy. Considering poor correlation of drug packs with treatment guidelines for H pylori, adherence to antimicrobial treatment and proper disposal of antimicrobials is warrant. Discussing adherence to antimicrobial treatment with patients should be introduced as a standard of patient care and education.
Effects of aripiprazole on circadian prolactin secretion related to pharmacogenetics in healthy volunteers
Authors: Koller Dora , Belmonte Carmen , Saiz‐Rodríguez Miriam , Zubiaur Pablo , Román Manuel , Ochoa Dolores , Abad‐Santos Francisco
Published: September 2019

Aripiprazole treatment in schizophrenic patients was previously associated with lower or normalized prolactin levels. Genetic variants in cytochrome P450 (CYP) (CYP2D6), dopamine receptor (DRD2, DRD3) and serotonin receptor (HTR2A, HTR2C) genes were previously associated with antipsychotic‐induced hyperprolactinaemia. Our aim was to evaluate whether aripiprazole affects prolactin secretion and its relationship with pharmacogenetics. Thirty‐one healthy volunteers receiving a 10‐mg single oral dose of aripiprazole were genotyped for 12 polymorphisms in CYP2D6, DRD2, DRD3, HTR2A and HTR2C genes by qPCR. Aripiprazole and dehydro‐aripiprazole plasma concentrations were measured by HPLC‐MS/MS. Prolactin concentrations of the 31 volunteers taking aripiprazole and 12 volunteers receiving ibuprofen were determined by ELISA. Prolactin concentrations after ibuprofen intake were considered as control, since it is known to cause no effect. Prolactin concentrations were slightly higher in the aripiprazole group compared to the ibuprofen group. All prolactin pharmacokinetic parameters were higher in females than in males. CYP2D6 poor and intermediate metabolizers had notably higher prolactin Cmax and AUC0‐12 than normal and ultrarapid metabolizers. The DRD3 rs6280 polymorphism affected prolactin levels: volunteers carrying Ser/Ser genotype had significantly lower prolactin levels than volunteers carrying the Gly allele. Furthermore, HTR2C rs3813929 C/C homozygotes had significantly lower prolactin levels than T allele carriers. Nevertheless, aripiprazole did increase prolactin levels compared to ibuprofen.
microRNA‐218‐5p plays a protective role in eosinophilic airway inflammation via targeting δ‐catenin, a novel catenin in asthma
Authors: Liang Yuxia , Feng Yuchen , Wu Wenliang , Chang Chenli , Chen Dian , Chen Shengchong , Zhen Guohua
Published: September 2019

Background

microRNA (miR)‐218‐5p is involved in cigarette smoke‐induced airway inflammation. In our earlier asthma epithelial miRNA profiling data, miR‐218‐5p was the top 2 down‐regulated miRNA. We hypothesize that miR‐218‐5p plays a role in asthma airway inflammation.

Objective

To unveil the role of miR‐218‐5p and its target gene in asthma airway inflammation.

Methods

We measured miR‐218‐5p expression in bronchial brushings of asthma patients (n = 50) and healthy controls (n = 15), and analysed the correlations between miR‐218‐5p expression and airway eosinophilia. We examined whether CTNND2 was a target of miR‐218‐5p, and the expression of 12 catenin family members in bronchial brushings, in cultured human bronchial epithelial (HBE) cells and BEAS‐2B cells. We explored the role of miR‐218‐5p‐CTNND2 pathway using a murine model of allergic airway inflammation.

Results

Epithelial miR‐218‐5p expression was significantly decreased and negatively correlated with eosinophils in induced sputum and bronchial biopsies, and other type 2 biomarkers in asthma patients. We verified that CTNND2 (encoding δ‐catenin) was a target of miR‐218‐5p. Remarkably, CTNND2 was the most significantly up‐regulated catenin compared with the other 11 catenin family members in bronchial brushings of asthma patients, IL‐13‐stimulated HBE and BEAS‐2B cells. Moreover, epithelial CTNND2 expression positively correlated with airway eosinophilia in asthma. Airway mmu‐miR‐218‐5p expression was also decreased, and Ctnnd2 expression was increased in a murine model of allergic airway inflammation. Intriguingly, mmu‐miR‐218‐5p overexpression suppressed airway hyperresponsiveness, eosinophilic airway inflammation and Ctnnd2 up‐regulation in the mouse model. Finally, perturbation of miR‐218‐5p or CTNND2 expression significantly altered chemokine CCL26 expression in the cell cultures and the mouse model.

Conclusions and Clinical Relevance

Epithelial miR‐218‐5p plays a protective role in eosinophilic airway inflammation via targeting CTNND2, a novel catenin in asthma, and suppressing chemokine CCL26 expression.
Diazoxide‐induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: Recommendations from a multicentre study in the United Kingdom
Authors: Chen Suet Ching , Dastamani Antonia , Pintus Donatella , Yau Daphne , Aftab Sommayya , Bath Louise , Swinburne Craig , Hunter Lindsey , Giardini Alessandro , Christov Georgi , Senniappan Senthil , Banerjee Indraneel , Shaikh Mohamad Guftar , Shah Pratik
Published: September 2019

Objective

Diazoxide is first‐line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide‐induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide‐induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide‐treated patients with HH.

Design and Patients

Retrospective cohort study involving four UK regional HH centres; review of case notes of HH patients on diazoxide.

Measurements

The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment‐related risk factors were analysed for association.

Results

Thirteen (6 men) of 177 HH diazoxide‐treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months. Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019).

Conclusion

Pulmonary hypertension can occur in 7% of diazoxide‐treated HH patients. Risk factors include the presence of congenital heart disease and fluid overload. Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops.
Gestational diabetes and acromegaly: Single‐centre experience of 14 pregnancies
Authors: Vialon Magaly , Grunenwald Solange , Mouly Céline , Vezzosi Delphine , Bennet Antoine , Gourdy Pierre , Caron Philippe J.
Published: September 2019

Introduction

The prevalence of gestational diabetes (GD) in women with acromegaly is rarely reported. The aims of this study were to evaluate the prevalence of GD in acromegalic women submitted to a systematic screening for GD and then to compare women with or without GD.

Patients and methods

We studied 14 pregnancies in 11 women (34.0 ± 3.6 years) treated with somatostatin analogues after a pituitary surgery (n = 6) or as primary (n = 5) therapy, and treatment was discontinued at the time of pregnancy diagnosis for 13 pregnancies. One woman was diagnosed with acromegaly during pregnancy and was treated with octreotide LAR between 12 and 18 weeks of gestation. Before pregnancy, no women had diabetes mellitus, and GH/IGF‐1 hypersecretion was uncontrolled in 6 women.

Results

Gestational diabetes was diagnosed during 7 pregnancies (50%) in 6 women (one woman had GD during her 2 pregnancies), according to fasting blood glucose (n = 5) or to an oral glucose tolerance test (n = 2). Before pregnancy, IGF‐1 was not controlled in 4 GD+ and in 2 GD− women. Women with GD were not significantly older and had increased pregestational BMI (P = .02), with a more frequent family history of type 2 diabetes, no personal history of GD but of macrosomia for one patient.

Conclusion

The prevalence of GD in our women is higher than that reported in the literature, probably resulting from the systematic GD screening and to the age of women. Therefore, routine screening of GD should be considered in women with acromegaly, particularly in those with risk factors for GD and with uncontrolled IGF‐1 levels before pregnancy.
Detection of t(14;18)(q32;q21) for IgH/BCL2 in central nervous system tumor‐like lesions with chronic perivascular inflammation
Authors: Shishido‐Hara Yukiko , Yazawa Takuya , Chiba Tomohiro , Kojima Kaoruko , Ishii Jun , Kobayashi Keiichi , Lee Jeung‐Hun , Sumiishi Ayumi , Tsuchiya Kazuhiro , Uchihara Toshiki , Shiokawa Yoshiaki , Takayama Nobuyuki , Nagane Motoo , Kamma Hiroshi
Published: September 2019

Objectives

There exist central nervous system tumor‐like lesions, resembling glioma on magnetic resonance imaging, although pathology shows active perivascular inflammation on biopsied brain tissues. As pathological diagnostic criteria have not been established, the nature of inflammatory cells was analyzed.

Methods

Biopsied brain tissues from tumor‐like inflammatory lesions were first studied histopathologically. Inflammatory cells were evaluated with immunohistochemistry and fluorescence in situ hybridization, and their molecular features were also analyzed with BIOMED‐2 multiplex polymerase chain reaction and sequencing of polymerase chain reaction products.

Results

Both B and T cells were infiltrated in the perivascular area, and BIOMED‐2 multiplex polymerase chain reaction detected the translocation t(14;18)(q32;q21); the fused IgH/BCL2 genes in all four patients. Fluorescence in situ hybridization showed juxtaposed IgH and BCL2 signals in 8% of perivascular cells in case 1, and 15% in case 4. Only a small number of cells were positive for CD10, BCL6 or MUM‐1; whether the translocation‐bearing cells were of nodal germinal center origin was not concluded. The fused IgH/BCL2 gene sequences were the same in four patients, which was contrasted with nodal follicular lymphoma with diversity in t(14;18)(q32;q21) patterns. Analysis of B‐cell receptor and did not show monoclonal proliferation of either B cells, but the T‐cell population appeared to be clonally restricted in one patient.

Conclusions

The chromosomal translocation t(14;18)(q32;q21) for IgH/BCL2 was detected in central nervous system tumor‐like inflammatory lesions. All patients responded well to the corticosteroid therapy and had a good prognosis. As the perivascular cells bearing t(14;18)(q32;q21) are small in number, the pathological significance remains unknown.
The relationship between dental implant papilla and dental implant mucosa around single‐tooth implant in the esthetic area: A retrospective study
Authors: Garabetyan Julia , Malet Jacques , Kerner Stéphane , Detzen Laurent , Carra Maria Clotilde , Bouchard Philippe
Published: September 2019

Objective

The aim of the present study was (a) to evaluate the relationship between dental implant mucosa and dental implant papilla levels; and (b) to identify the clinical parameters associated with peri‐implant soft tissue stability over time.

Materials and methods

This is a retrospective study on a cohort of patients seeking a single‐tooth implant therapy in a private practice in the Paris area. Two independent examiners analyzed photographs and radiographs taken the day of definitive crown load (baseline) and the last follow‐up visit (at least 12 months later) in order to measure four peri‐implant soft and hard tissue parameters.

Results

Seventy‐four patients corresponding to 90 implants were analyzed. During a mean follow‐up of 53.88 months, five implants (5.6%) presented with an apical displacement of the mid‐facial marginal mucosal level of at least 1 mm. Changes in the mid‐facial mucosa level were explained by changes in (a) the keratinized tissue height over time (p < .0001); (b) changes in the papilla height (p < .0001); and (c) by the periodontal phenotype (p = .007). A significant difference between papillae that gain in height (n = 85) and papilla that lost height (n = 78) was observed concerning (a) the timing of the implant placement (p = .019); and (b) the presence of an incomplete papilla fill (distance from the top of the papilla to the contact point) at baseline (p = .004).

Conclusions

The present findings indicate a dependent association between dental implant mucosa and dental implant papilla levels. Stability of peri‐implant soft tissues depends on periodontal phenotype, keratinized tissue height and papilla height.
Uncertainty versus prediction error in Pavlovian fear conditioning: Commentary on Walker et al. (2019)
Authors: Tronson Natalie C.
Published: September 2019

Commentary on Walker RA, Wright KM, Jhou TC, McDannald MA. The ventrolateral periaqueductal grey updates fear via positive prediction error. Eur J Neurosci. 2020;51:866–880. https://doi.org/10.1111/ejn.14536
Lack of gene flow between Phytophthora infestans populations of two neighboring countries with the largest potato production
Authors: Wang Yan‐Ping , Xie Jia‐Hui , Wu E‐Jiao , Yahuza Lurwanu , Duan Guo‐Hua , Shen Lin‐Lin , Liu Hao , Zhou Shi‐Hao , Nkurikiyimfura Oswald , Andersson Björn , Yang Li‐Na , Shang Li‐Ping , Zhu Wen , Zhan Jiasui
Published: September 2019

Gene flow is an important evolutionary force that enables adaptive responses of plant pathogens in response to changes in the environment and plant disease management strategies. In this study, we made a direct inference concerning gene flow in the Irish famine pathogen Phytophthora infestans between two of its hosts (potato and tomato) as well as between China and India. This was done by comparing sequence characteristics of the eukaryotic translation elongation factor 1 alpha (eEF‐1α) gene, generated from 245 P. infestans isolates sampled from two countries and hosts. Consistent with previous results, we found that eEF‐1α gene was highly conserved and point mutation was the only mechanism generating any sequence variation. Higher genetic variation was found in the eEF‐1α sequences in the P. infestans populations sampled from tomato compared to those sampled from potato. We also found the P. infestans population from India displayed a higher genetic variation in the eEF‐1α sequences compared to China. No gene flow was detected between the pathogen populations from the two countries, which is possibly attributed to the geographic barrier caused by Himalaya Plateau and the minimum cross‐border trade of potato and tomato products. The implications of these results for a sustainable management of late blight diseases are discussed.
The influence of MC1R on dermal morphological features of photo‐exposed skin in women revealed by reflectance confocal microscopy and optical coherence tomography
Authors: Guida Stefania , Ciardo Silvana , De Pace Barbara , De Carvalho Nathalie , Peccerillo Francesca , Manfredini Marco , Farnetani Francesca , Chester Johanna , Kaleci Shaniko , Manganelli Michele , Guida Gabriella , Pellacani Giovanni
Published: September 2019

Background

The melanocortin 1 receptor (MC1R) gene is one of the major determinants of skin pigmentation. It is a highly polymorphic gene and some of its polymorphisms have been related to specific skin phenotypes, increased risk of skin cancers and skin photoageing. Currently, its contribution to changes in dermal features in photo‐exposed skin is unknown.

Objective

The main objective of this study is to evaluate the potential correlation between MC1R status and specific healthy photo‐exposed skin characteristics.

Materials and methods

Skin facial features were estimated by evaluation with standard digital photography with automated features count, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in 100 healthy women. Skin of the forearms was used as a control.

Results

The study found an association between RHC MC1R polymorphisms and dermal features in photo‐exposed areas being represented by increased vessel density and pixel density in OCT (P = .025 and P = .001, respectively) and increased coarse collagen in RCM (P = .034), as compared to non‐RHC subjects. To our knowledge this is previously unreported. Additionally, previously reported correlations between light hair colour and pigmented spots with MC1R RHC polymorphisms have been confirmed.

Conclusions

Our results suggest the role of RHC MC1R variants in dermal variations of facial skin, as compared to non‐RHC variants. To our knowledge this is previously unreported.