bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefits from hazards, benefits from nothing, and benefits from benefits: the combined effects of five quaternary ammonium compounds to Vibrio qinghaiensis Q67
Authors: Mo Ling-Yun , Liu Yong-An , Zhu Jie , Qin Li-Tang , Liang Yan-Peng , Zeng Hong-Hu
Published: March 2020

Background

Co-exposure of multiple quaternary ammonium compounds (QACs) is widely present in the aquatic environment. The knowledge about their toxicities to microorganism at low concentration is lacking. This study aims to test the toxic response of Vibrio qinghaiensis Q67 (12-h exposure) to individual and mixtures of QACs by the long-term microplate toxicity analysis method (L-MTA).

Results

Hormetic effects were observed for five individual QACs at 12-h exposure of Vibrio qinghaiensis Q67. The maximum stimulation effect of − 339.66% was present in the 0.00561 mol/L tetraethylammonium bromide solution. A stimulation effect (− 23.55%) was detected when each of QACs in the five-component mixture was present at 50% effect concentration (“benefits from hazards”). In addition, significant stimulation effects (− 96.28%) were observed for five QACs combined at the zero-effect point concentration (“benefits from nothing”). Further, a significant stimulation effect (− 406.16%) was observed when each of QACs was co-exposed at its maximum stimulation effect concentration. This phenomenon was termed “benefits from benefits”.

Conclusions

The results suggest that both single and mixture of QACs presented hormetic effects. Benefits from hazards, benefits from nothing, and benefits from benefits were observed for the QACs mixtures.
Mobility styles and car sharing use in Europe: attitudes, behaviours, motives and sustainability
Authors: Ramos Érika Martins Silva , Bergstad Cecilia Jakobsson , Chicco Andrea , Diana Marco
Published: March 2020

What are the profiles of both users and non-users of car sharing in European cities regarding their travel patterns and psychological aspects? Two subsamples (1519 users and 3695 non-users of car sharing) participated in a survey, translated into seven languages, with 36 questions regarding attitudes towards car sharing, the environment, political orientation, personal norms, frequency of use of different transport modes and transport mode choice for different travel purposes. Through a hierarchical cluster analysis, five distinct mobility styles were identified, with no a priori restriction of the number of clusters. The mobility styles were further characterised by sociodemographic variables and by the motives for making use of car sharing. This paper discusses the implications of research based decision-making and urban planning in a way that guarantees long-term human and environmental security.
Correction to: Minicircle DNA vector expressing interferon-lambda-3 inhibits hepatitis B virus replication and expression in hepatocyte-derived cell line
Authors: Guo Xiaoyan , Chen Dianke , Cai Qingxian , Huang Zhanlian , Xu Wenxiong , Peng Liang , Chen Ping
Published: March 2020

Following publication of the original article [1], the authors reported an error that occurred during the production process.
Genome-wide identification of CNGC genes in Chinese jujube (Ziziphus jujuba Mill.) and ZjCNGC2 mediated signalling cascades in response to cold stress
Authors: Wang Lixin , Li Min , Liu Zhiguo , Dai Li , Zhang Mengling , Wang Lili , Zhao Jin , Liu Mengjun
Published: March 2020

Backgrounds

Cyclic nucleotide gated channels (CNGCs) play multifaceted roles in plant physiological processes, especially with respect to signalling processes, plant development, and responses to environmental stresses. However, little information is known about the CNGC family in the large cosmopolitan familyRhamnaceae, which has strong tolerance to biotic and abiotic stresses.

Results

In the current study, a total of 15ZjCNGCswhich located on 7 chromosomes were firstly identified in Chinese jujube (Ziziphus jujubaMill.), the most important species ofRhamnaceaein terms of economic and ecological values. Phylogenetic analysis showed that theseZjCNGCscould be classified into four groups,ZjCNGC12belonged to group IVA, andZjCNGC13,14,15belonged to group IVB. In addition, the paralogous and orthologous homology duplication ofZjCNGC15occurred during the evolutionary process. The characteristics ofZjCNGCsregarding to exon-intron numbers and post-translational modifications showed diversified structures and functions. Motif composition and protein sequence analysis revealed that the phosphate-binding cassette and hinge regions were conserved among ZjCNGCs. Prediction of thecis-acting regulatory elements and expression profiles by real-time quantitative PCR analysis showed that some of theZjCNGCsresponded to environmental changes, especiallyZjCNGC2, which was significantly downregulated in response to cold stress, andZjCNGC4was highly induced in response to cold, salt and alkaline stresses.ZjCNGC13and14were highly induced in the phytoplasma-resistant cultivar and downregulated in the susceptible cultivar. Furthermore,ZjCNGC2could be regulated by cAMP treatment, microtubule changes and interact with ZjMAPKK4, which suggested that cAMP and microtubule might play important roles inZjCNGC2mediatedZjMAPKK4signalling transduction involved in cold stress.

Conclusions

The identification and classification analysis ofZjCNGCswere firstly reported, and some key individualZjCNGCsmight play essential roles in the response to biotic and abiotic stresses, especiallyZjCNGC2mediatedZjMAPKK4signalling transduction involved in cold stress. This systematic analysis could provide important information for further functional characterization ofZjCNGCswith the aim of breeding stress-resistant cultivars.
Enterococcus faecalis-associated lung abscess in a male adolescent- a case report
Authors: Mendes Ana Raquel , Costa António , Ferreira Helena , Ferreira Cristina
Published: March 2020

Background

Enterococci are rarely considered pulmonary pathogens; they are usually regarded as colonizers of the airway. The authors present the case of a previously healthy male adolescent, with complaints of fatigue and chest pain, who was diagnosed with Enterococcus faecalis-associated acute primary lung abscess.

Case presentation

A previously healthy 17-year old boy was admitted to the pediatric ward due to a one-week history of fatigue, inspiratory left side chest pain, dry cough and nasal obstruction. On admission at the emergency department, he was afebrile, with no signs of respiratory distress, but with diminished breath sounds on the left side. A chest x-ray showed a round opacity on the posterior basal segment of the left lower lobe; he was discharged with oral amoxicillin 1000 mg three times a day with the diagnosis of community-acquired pneumonia. Due to the worsening of the productive cough with purulent stinking sputum he was re-evaluated after 4 days. Laboratory studies showed a leukocyte count of 15200/uL and a c-reactive protein of 172 mg/l. The chest computed tomography scan was suggestive of a consolidation of the left lower lobe base and a central abscess. An intravenous course of ceftriaxone and clindamycin was initiated, with a favourable clinical evolution. The bronchofibroscopy performed on day four after his admission revealed the presence of a tracheal bronchus and numerous purulent secretions. Culture examination of bronchoalveolar lavage fluid samples was positive (> 10^5) for Enterococcus faecalis. No complications were registered during his stay in the pediatric ward. He was discharged after a 14-day course of intravenous ceftriaxone and clindamycin, with the recommendation to complete a four-week course of oral amoxicillin/clavulanic acid. On his reevaluation 4 weeks after his discharge, he was asymptomatic.

Conclusion

This case report highlights the importance of considering Enterococcus faecalis as an etiologic agent in cases of non-resolving or complicated cases of pneumonia, such as lung abscesses, even in young patients with no comorbidities or risk factors.
Development and validation of knowledge, attitude and practice questionnaire for prevention of respiratory tract infections among Malaysian Hajj pilgrims
Authors: Goni Mohammed Dauda , Naing Nyi Nyi , Hasan Habsah , Wan-Arfah Nadiah , Deris Zakuan Zainy , Arifin Wan Nor , Hussin Tengku Mohammad Ariff Raja , Abdulrahman Abdulwali Sabo , Baaba Aisha Abubakar , Arshad Muhammad Rafie
Published: March 2020

Background

Hajj pilgrimage faces numerous challenges including a high prevalence of respiratory tract infection as well as its prevention strategies. The aim of this study was to develop and validate a questionnaire to evaluate knowledge, attitude and practice (KAP) towards respiratory tract infections (RTIs) prevention among Malaysian Hajj pilgrims.

Methods

This study was conducted among Malaysian Umrah pilgrims in Malaysia from Kuala Lumpur and Kelantan. The questionnaire then underwent a series of validation process that included content, face validity and exploratory part. Item response theory (IRT) analysis was utilized for the validation of the knowledge domain. The attitude and practice were validated using the exploratory factor analysis (EFA).

Results

The validation process resulted in a questionnaire that comprised of four main sections: demography, knowledge, attitude, and practice. Following IRT analysis of the knowledge domain, all items analyzed were within the acceptable range of difficulty and discrimination. The Kaiser-Meyer-Olkin measure of sampling adequacy (KMO) was 0.72 and 0.84 for attitude and practice domain respectively and Bartlett’s test of Sphericity for both domains were highly significant (P < 0.001). The factor analysis resulted in two factors with total of 12 items in attitude domain, and 2 factors with total of 13 items in the practice domain with satisfactory factor loading (> 0.3). The Cronbach’s alpha for reliability of the knowledge, attitude and practice domains all showed acceptable values of > 0.6 (0.92, 0.77 and 0.85).

Conclusion

The findings of this validation and reliability study showed that the developed questionnaire had a satisfactory psychometric property for measuring KAP of Malaysian Hajj pilgrims.
Ectopic bronchogenic cyst of the gastric cardia considered to be a gastrointestinal stromal tumor before surgery: a case report
Authors: Xiao Jianchun , Zhang Ruopeng , Chen Wanqi , Wu Bin
Published: March 2020

Background

We herein report a rare case of an ectopic bronchogenic cyst of the gastric cardia. The initial diagnosis was a gastrointestinal stromal tumor (GIST); however, postoperative pathologic examination confirmed that it was a bronchogenic cyst.

Case presentation

A 62-year-old woman visited our hospital for abdominal pain. The diagnosis prior to surgery was a GIST. Computed tomography imaging showed that the mass was located in the gastric cardia on the side of the lesser curvature. During the surgical exploration, it was noted that the tactility of the mass was not consistent with a GIST. Thus, we decided to perform local resection of the mass and part of the gastric wall without wedge resection. The pathological examination revealed a bronchogenic cyst.

Conclusions

This case suggests that a bronchogenic cyst should be considered as a differential diagnosis of a GIST. It is also a unusual but necessary situation should be considered when explaining the etiology of a bronchogenic cyst.
Anti-melanogenic activity of Myristica fragrans extract against Aspergillus fumigatus using phenotypic based screening
Authors: Hoda Shanu , Vermani Maansi , Joshi Rajesh K. , Shankar Jata , Vijayaraghavan Pooja
Published: March 2020

Background

Aspergillus fumigatus, an opportunistic fungal pathogen is associated with a wide array of diseases. It produces 1, 8-dihydroxy naphthalene (DHN) melanin that imparts greenish grey color to conidia and is an important virulence factor. It masks various molecular patterns associated withA. fumigatusand protects the fungus from host immune system.Myristica fragrans, enriched with secondary metabolites has been traditionally used for the treatment of infectious and inflammatory diseases. The present study was aimed to explore the anti-melanogenic effect ofM. fragransextracts onA. fumigatus.

Methods

M. fragransextracts (hexane, chloroform, methanol and ethanol) were prepared through polarity guided extraction. Phytochemical analysis was performed to detect the chemical constituents of the extracts. The minimum effective concentration (MEC) of the extracts againstA. fumigatusmelanin was determined by broth micro-dilution assay.Various virulence factors were assayed by spectrophotometric methods. Electron microscopic studies were performed to evaluate the effect of the hexane extract ofM. fragransonA. fumigatuscell surface morphology. The major active compounds of the extract were detected by gas chromatography-mass spectrometry (GC-MS). Docking was performed to study the interaction between the major identified compounds and the ketosynthase domain of polyketide synthase protein.

Results

The results indicated that the hexane extract ofM. fragransinhibited melanin production (76.09%), reduced ergosterol content (83.63%) and hydrophobicity of the cell (72.2%) at the MEC of 0.078 mg/mL. Altered conidial surface, disappearance of protrusions and absence of melanin layer on outer cell surface was observed in electron microscopy. Forty-two compounds were identified by GC-MS. The main constituents were identified as sabinene (12.2%), linoleic acid (11.7%), hexadecanoic acid (10.5%), safrole (8.1%) and elemicin (7.8%). Docking studies revealed that hexadecanoic acid, its derivative compound cis-9-hexadecenal and isoeugenol have lower binding energy forming proper hydrogen bond with ketosynthase domain of polyketide synthase protein.

Conclusion

The study concludes that the extract ofM. fragranshas potential antifungal properties that can be explored in combination with available antifungals. This combination approach may be helpful for large number of patients suffering withA. fumigatusinfections.
The draft nuclear genome sequence and predicted mitochondrial proteome of Andalucia godoyi, a protist with the most gene-rich and bacteria-like mitochondrial genome
Authors: Gray Michael W. , Burger Gertraud , Derelle Romain , Klimeš Vladimír , Leger Michelle M. , Sarrasin Matt , Vlček Čestmír , Roger Andrew J. , Eliáš Marek , Lang B. Franz
Published: March 2020

Background

Comparative analyses have indicated that the mitochondrion of the last eukaryotic common ancestor likely possessed all the key core structures and functions that are widely conserved throughout the domain Eucarya. To date, such studies have largely focused on animals, fungi, and land plants (primarily multicellular eukaryotes); relatively few mitochondrial proteomes from protists (primarily unicellular eukaryotic microbes) have been examined. To gauge the full extent of mitochondrial structural and functional complexity and to identify potential evolutionary trends in mitochondrial proteomes, more comprehensive explorations of phylogenetically diverse mitochondrial proteomes are required. In this regard, a key group is the jakobids, a clade of protists belonging to the eukaryotic supergroup Discoba, distinguished by having the most gene-rich and most bacteria-like mitochondrial genomes discovered to date.

Results

In this study, we assembled the draft nuclear genome sequence for the jakobidAndalucia godoyiand used a comprehensive in silico approach to infer the nucleus-encoded portion of the mitochondrial proteome of this protist, identifying 864 candidate mitochondrial proteins. TheA. godoyimitochondrial proteome has a complexity that parallels that of other eukaryotes, while exhibiting an unusually large number of ancestral features that have been lost particularly in opisthokont (animal and fungal) mitochondria. Notably, we find no evidence that theA. godoyinuclear genome has or had a gene encoding a single-subunit, T3/T7 bacteriophage-like RNA polymerase, which functions as the mitochondrial transcriptase in all eukaryotes except the jakobids.

Conclusions

As genome and mitochondrial proteome data have become more widely available, a strikingly punctuate phylogenetic distribution of different mitochondrial components has been revealed, emphasizing that the pathways of mitochondrial proteome evolution are likely complex and lineage-specific. Unraveling this complexity will require comprehensive comparative analyses of mitochondrial proteomes from a phylogenetically broad range of eukaryotes, especially protists. The systematic in silico approach described here offers a valuable adjunct to direct proteomic analysis (e.g., via mass spectrometry), particularly in cases where the latter approach is constrained by sample limitation or other practical considerations.
Evolution of metabolic capabilities and molecular features of diplonemids, kinetoplastids, and euglenids
Authors: Butenko Anzhelika , Opperdoes Fred R. , Flegontova Olga , Horák Aleš , Hampl Vladimír , Keeling Patrick , Gawryluk Ryan M. R. , Tikhonenkov Denis , Flegontov Pavel , Lukeš Julius
Published: March 2020

Background

The Euglenozoa are a protist group with an especially rich history of evolutionary diversity. They include diplonemids, representing arguably the most species-rich clade of marine planktonic eukaryotes; trypanosomatids, which are notorious parasites of medical and veterinary importance; and free-living euglenids. These different lifestyles, and particularly the transition from free-living to parasitic, likely require different metabolic capabilities. We carried out a comparative genomic analysis across euglenozoan diversity to see how changing repertoires of enzymes and structural features correspond to major changes in lifestyles.

Results

We find a gradual loss of genes encoding enzymes in the evolution of kinetoplastids, rather than a sudden decrease in metabolic capabilities corresponding to the origin of parasitism, while diplonemids and euglenids maintain more metabolic versatility. Distinctive characteristics of molecular machines such as kinetochores and the pre-replication complex that were previously considered specific to parasitic kinetoplastids were also identified in their free-living relatives. Therefore, we argue that they represent an ancestral rather than a derived state, as thought until the present. We also found evidence of ancient redundancy in systems such as NADPH-dependent thiol-redox. Only the genusEuglenapossesses the combination of trypanothione-, glutathione-, and thioredoxin-based systems supposedly present in the euglenozoan common ancestor, while other representatives of the phylum have lost one or two of these systems. Lastly, we identified convergent losses of specific metabolic capabilities between free-living kinetoplastids and ciliates. Although this observation requires further examination, it suggests that certain eukaryotic lineages are predisposed to such convergent losses of key enzymes or whole pathways.

Conclusions

The loss of metabolic capabilities might not be associated with the switch to parasitic lifestyle in kinetoplastids, and the presence of a highly divergent (or unconventional) kinetochore machinery might not be restricted to this protist group. The data derived from the transcriptomes of free-living early branching prokinetoplastids suggests that the pre-replication complex of Trypanosomatidae is a highly divergent version of the conventional machinery. Our findings shed light on trends in the evolution of metabolism in protists in general and open multiple avenues for future research.
Coverage and effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine–pyrimethamine (IPTp-SP) on adverse pregnancy outcomes in the Mount Cameroon area, South West Cameroon
Authors: Anchang-Kimbi Judith K. , Kalaji Laken N. , Mbacham Harry F. , Wepnje Godlove B. , Apinjoh Tobias O. , Ngole Sumbele Irene U. , Dionne-Odom Jodie , Tita Alan T. N. , Achidi Eric A.
Published: March 2020

Background

Growing concerns about the waning efficacy of IPTp-SP warrants continuous monitoring and evaluation. This study determined coverage of IPTp-SP and compared the effectiveness of the 3-dose to 2-dose regimen on placental malaria (PM) infection and low birth weight (LBW) in the Mount Cameroon area.

Methods

Consenting pregnant women were enrolled consecutively through a cross-sectional survey at delivery at four antenatal clinics, two each from semi-rural and semi-urban settings from November 2016 to December 2017. Reported IPTp-SP use, demographic and antenatal clinic (ANC) data of the mothers and neonate birth weights were documented. Maternal haemoglobin concentration was measured using a haemoglobinometer and PM infection diagnosed by placental blood microscopy. Logistic regression analysis was used to model study outcomes.

Results

Among the 465 parturient women enrolled, 47.0% (203), 34.7% (150), 18.3% (79) and 7.1% (33) reported uptake of ≥ 3, 2.1 dose(s) and no SP, respectively. Uptake of ≥ 3 doses varied significantly (p < 0.001) according to type of medical facility, timing of ANC initiation and number of ANC visits. The prevalence of PM was 18.5% where uptake of ≥ 3 SP doses (AOR = 2.36: 95% CI  1.41–4.87), primiparity (AOR = 2.13: 95% CI  1.19–3.81), semi-rural setting (AOR = 1.85: 95% CI  1.12–3.04) increased odds of infection. Also, three or more dosing was associated (p < 0.001) with increased PM density notably among women from semi-urban areas. Compared with third trimester, ANC initiation in the second trimester (AOR: 0.39: 95% CI  0.20–0.74) lower odds of infection. The prevalence of LBW infants was 7.3% and were generally those of anaemic (AOR: 4.6: 95% CI  1.03–20.57) and semi-rural (AOR: 5.29: 95% CI  1.73–16.15) women. Although ≥ 3 (AOR: 0.31: 95% CI  0.11–0.87) and 2 (AOR: 0.32: 95% CI  0.11–0.93) doses of SP was associated with lower odds of LBW, ≥ 3 doses were not associated with additional increase in birth weight nor maternal haemoglobin levels when compared with 2 doses.

Conclusion

In the Mount Cameroon area, reported uptake of IPTp with ≥ 3 SP doses did not provide observable prophylactic benefits. SP resistance efficacy studies are necessary.
LincRNA-EPS in biomimetic vesicles targeting cerebral infarction promotes inflammatory resolution and neurogenesis
Authors: Zhang Benping , Li Qian , Jia Shuwei , Li Feng , Li Qingsong , Li Jiebing
Published: March 2020

Background

Inflammatory damage following stroke aggravates brain damage, resulting in long-term neurological sequelae. The purpose of this study was to identify ways to reduce inflammatory reactions and to accelerate neuron regeneration after cerebral apoplexy.

Methods

We formulated a biomimetic vesicle, the leukosome, constituted by liposome, artificial long intergenic noncoding RNA (lincRNA)-EPS, and membrane proteins derived from macrophages and their physical–chemical characteristics were evaluated. Migration distance and cytotoxic levels were measured to determine the effect of lncEPS-leukosomes on lipopolysaccharide-activated microglia. An in vivo transient middle cerebral artery occlusion/reperfusion (tMCAO) model was established in mice, which were treated with lncEPS-leukosomes. Vesicle seepage, infiltration of inflammatory cells, cytotoxic levels in the cerebrospinal fluid, and neural stem cell (NSC) density were measured.

Results

Biomimetic vesicles with a homogeneous size increased lincRNA-EPS levels in activated microglia by 77.9%. In vitro studies showed that lincRNA-EPS inhibited the migration and cytotoxic levels of activated microglia by 63.2% and 43.6%, respectively, which promoted NSC proliferation and anti-apoptotic ability. In vivo data showed that leukosomes targeted to inflamed sites and lncEPS-leukosomes decreased the infiltration of inflammatory cells and cytotoxic levels by 81.3% and 48.7%, respectively. In addition, lncEPS-leukosomes improved neuron density in the ischemic core and boundary zone after tMCAO.

Conclusions

The biomimetic vesicles formulated in this study targeted inflammatory cells and accelerated neuron regeneration by promoting inflammation resolution. This study may provide a promising treatment approach for accelerated neuron regeneration after cerebral apoplexy.
Comprehensive analysis of differential immunocyte infiltration and the potential ceRNA networks during epicardial adipose tissue development in congenital heart disease
Authors: Ma Li , Shi Wanting , Ma Xun , Zou Minghui , Chen Weidan , Li Wenlei , Zou Rongjun , Chen Xinxin
Published: March 2020

Background

To detect the development, function and therapeutic potential of epicardial adipose tissue (EAT); analyze a related gene expression dataset, including data from neonates, infants, and children with congenital heart disease (CHD); compare the data to identify the codifferentially expressed (DE) mRNAs and lncRNAs and the corresponding miRNAs; generate a potential competitive endogenous RNA (ceRNA) network; and assess the involvement of immunocyte infiltration in the development of the EAT.

Methods

Multiple algorithms for linear models for microarray data algorithms (LIMMA), CIBERSORT, gene-set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used. The miRcode, miRDB, miRTarBase, and TargetScan database were used to construct the ceRNA network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DE mRNAs were performed.

Results

Thirteen co-DE mRNAs and 47 co-DE lncRNAs were subsequently identified. The related categories included negative regulation of myoblast differentiation, regulation of ion transmembrane transport, and heart development, which were primarily identified for further pathway enrichment analysis. Additionally, the hub ceRNA network in EAT development involving MIR210HG, hsa-miR-449c-5p, and CACNA2D4 was generated and shown to target monocyte infiltration.

Conclusion

These findings suggest that the pathways of myoblast differentiation and ion transmembrane transport may be potential hub pathways involved in EAT development in CHD patients. In addition, the network includes monocytes, MIR210HG, and CACNA2D4, which were shown to target the RIG-I-like receptor signaling pathway and PPAR signaling pathway, indicating that these factors may be novel regulators and therapeutic targets in EAT development.
Gender differences in hereditary hemorrhagic telangiectasia severity
Authors: Mora-Luján J. M. , Iriarte A. , Alba E. , Sánchez-Corral M. A. , Cerdà P. , Cruellas F. , Ordi Q. , Corbella X. , Ribas J. , Castellote J. , Riera-Mestre A.
Published: March 2020

Background

Gender differences in organ involvement and clinical severity have been poorly described in hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to describe differences in the severity of HHT manifestations according to gender.

Methods

Severity was measured according to Epistaxis Severity Score (ESS), Simple Clinical Scoring Index for hepatic involvement, a general HHT-score, needing for invasive treatment (pulmonary or brain arteriovenous malformations -AVMs- embolization, liver transplantation or Young’s surgery) or the presence of adverse outcomes (severe anemia, emergency department -ED- or hospital admissions and mortality).

Results

One hundred forty-two (58.7%) women and 100 (41.3%) men were included with a mean age of 48.9 ± 16.6 and 49 ± 16.5 years, respectively. Women presented hepatic manifestations (7.1% vs 0%) and hepatic involvement (59.8% vs 47%), hepatic AVMs (28.2% vs 13%) and bile duct dilatation (4.9% vs 0%) at abdominal CT, and pulmonary AVMs at thoracic CT (35.2% vs 23%) more often than men. The Simple Clinical Scoring Index was higher in women (3.38 ± 1.2 vs 2.03 ± 1.2), and more men were considered at low risk of harboring clinically significant liver disease than women (61% vs 25.3%). These differences were mantained when considering HHT1 and HHT2 patients separetely. Duodenal telangiectasia were more frequent in men than women (21% vs 9.8%). Invasive treatments were more frequently needed in women (28.2% vs 16%) but men needed attention at the ED more often than women (48% vs 28.2%), with no differences in ESS, HHT-score, anemia hospital admissions or mortality.

Conclusions

HHT women showed more severe hepatic involvement than men, also among HHT1 and HHT2 patients. Women had higher prevalence of pulmonary AVMs and needed invasive procedures more frequently, while men needed attention at the ED more often. These data might help physicians to individualize HHT patients follow-up.
Utilizing minimally purified secreted rAAV for rapid and cost-effective manipulation of gene expression in the CNS
Authors: Goodwin Marshall S. , Croft Cara L. , Futch Hunter S. , Ryu Daniel , Ceballos-Diaz Carolina , Liu Xuefei , Paterno Giavanna , Mejia Catalina , Deng Doris , Menezes Kimberly , Londono Laura , Arjona Kefren , Parianos Mary , Truong Van , Rostonics Eva , Hernandez Amanda , Boye Sanford L. , Boye Shannon E. , Levites Yona , Cruz Pedro E. , Golde Todd E.
Published: March 2020

Background

Recombinant adeno-associated virus (rAAV) is widely used in the neuroscience field to manipulate gene expression in the nervous system. However, a limitation to the use of rAAV vectors is the time and expense needed to produce them. To overcome this limitation, we evaluated whether unpurified rAAV vectors secreted into the media following scalable PEI transfection of HEK293T cells can be used in lieu of purified rAAV.

Methods

We packaged rAAV2-EGFP vectors in 30 different wild-type and mutant capsids and subsequently collected the media containing secreted rAAV. Genomic titers of each rAAV vector were assessed and the ability of each unpurified virus to transduce primary mixed neuroglial cultures (PNGCs), organotypic brain slice cultures (BSCs) and the mouse brain was evaluated.

Results

There was ~ 40-fold wide variance in the average genomic titers of the rAAV2-EGFP vector packaged in the 30 different capsids, ranging from a low ~ 4.7 × 1010 vector genomes (vg)/mL for rAAV2/5-EGFP to a high of ~ 2.0 × 1012 vg/mL for a capsid mutant of rAAV2/8-EGFP. In PNGC studies, we observed a wide range of transduction efficiency among the 30 capsids evaluated, with the rAAV2/6-EGFP vector demonstrating the highest overall transduction efficiency. In BSC studies, we observed robust transduction by wild-type capsid vectors rAAV2/6, 2/8 and 2/9, and by capsid mutants of rAAV2/1, 2/6, and 2/8. In the in vivo somatic brain transgenesis (SBT) studies, we found that intra-cerebroventricular injection of media containing unpurified rAAV2-EGFP vectors packaged with select mutant capsids resulted in abundant EGFP positive neurons and astrocytes in the hippocampus and forebrain of non-transgenic mice. We demonstrate that unpurified rAAV can express transgenes at equivalent levels to lysate-purified rAAV both in vitro and in vivo. We also show that unpurified rAAV is sufficient to drive tau pathology in BSC and neuroinflammation in vivo, recapitulating previous studies using purified rAAV.

Conclusions

Unpurified rAAV vectors secreted into the media can efficiently transduce brain cells in vitro and in vivo, providing a cost-effective way to manipulate gene expression. The use of unpurified virus will greatly reduce costs of exploratory studies and further increase the utility of rAAV vectors for standard laboratory use.
Study protocol for a randomized controlled trial: prophylactic swallowing exercises in head-and-neck cancer patients treated with (chemo)radiotherapy (PRESTO trial)
Authors:   Member of the Belgian PRESTO Group, Baudelet Margot , Van den Steen Leen , Duprez Fréderic , De Bodt Marc , Deschuymer Sarah , Goeleven Ann , Hutsebaut Isabel , Mariën Steven , Meersschout Sabine , Nevens Daan , Nuyts Sandra , Peeters Marc , Specenier Pol , Van den Brekel Michiel , van der Molen Lisette , Vandenbruaene Caroline , Vanderveken Olivier , Van Dinther Joost , Van Laer Carl , Vauterin Tom , Verstraete Hilde , Van Nuffelen Gwen
Published: March 2020

Background

Dysphagia is a common and serious complication after (chemo)radiotherapy (CRT) for head-and-neck cancer (HNC) patients. Prophylactic swallowing exercises (PSE) can have a significantly positive effect on post-treatment swallowing function. However, low adherence rates are a key issue in undermining this positive effect. This current randomized trial will investigate the effect of adherence-improving measures on patients’ swallowing function, adherence and quality of life (QOL).

Methods

This ongoing trial will explore the difference in adherence and swallowing-related outcome variables during and after PSE in HNC patients performing the same therapy schedule, receiving different delivery methods. One hundred and fifty patients treated in various hospitals will be divided into three groups. Group 1 performs PSE at home, group 2 practices at home with continuous counseling through an app and group 3 receives face-to-face therapy by a speech and language pathologist. The exercises consist of tongue-strengthening exercises and chin-tuck against resistance with effortful swallow. The Iowa Oral Performance Instrument and the Swallowing Exercise Aid are used for practicing. Patients are evaluated before, during and after treatment by means of strength measurements, swallowing and QOL questionnaires.

Discussion

Since low adherence rates undermine the positive impact of PSE on post-treatment swallowing function, there is need to develop an efficient PSE protocol maximizing adherence rates.

Trial registration

ISRCTN, ID: ISRCTN98243550. Registered retrospectively on 21 December 2018.
New codon 198 β-tubulin polymorphisms in highly benzimidazole resistant Haemonchus contortus from goats in three different states in Sudan
Authors: Mohammedsalih Khalid M. , Krücken Jürgen , Khalafalla Amna , Bashar Ahmed , Juma Fathel-Rahman , Abakar Adam , Abdalmalaik Abdalhakaim A. H. , Coles Gerald , von Samson-Himmelstjerna Georg
Published: March 2020

Background

Benzimidazole (BZ) resistance in gastrointestinal nematodes is a worldwide problem for livestock production, particularly in small ruminants. Assignment of the emergence of resistance using sensitive and reliable methods is required to adopt the correct strategies for control. In Sudan, BZ resistantHaemonchus contortuspopulations were recently reported in goats in South Darfur. This study aimed to provide additional data regarding albendazole efficacy and to describe the prevailing molecular BZ resistance mechanisms.

Methods

Faecal egg count reduction and egg hatch tests (EHT) were used to evaluate albendazole efficacy in three different areas of South Darfur using naturally (Rehed Al-Birdi and Tulus) and experimentally infected (Tulus and Um Dafuq) goats. Using samples from Central, East and South Darfur, pyro- and Sanger sequencing were used to detect the polymorphisms F167Y, E198A and F200Y inH. contortusisotype 1 β-tubulin in DNA extracted from pooled third-stage larval (L3) samples (n = 36) on days 0 and 10 during trials, and from pooled adult maleH. contortus(treated goats,n = 14; abattoirs,n = 83) including samples from populations previously found to be resistant in South Darfur.

Results

Albendazole efficacies at 5, 7.5 and 10 mg/kg doses were 73.5–90.2% on day 14 in natural and experimental infections while 12.5 mg/kg showed > 96.6% efficacy. EC50in the EHT were 0.8 and 0.11 µg/ml thiabendazole in natural and experimental infection trials, respectively. PCRs detectedHaemonchus,TrichostrongylusandCooperiain L3 samples from albendazole-treated goats.Haemonchus contortusallele frequencies in codons 167 and 200 using pyrosequencing assays were ≤ 7.4% while codon 198 assays failed. Sanger sequencing revealed five novel polymorphisms at codon 198. Noteworthy, an E198L substitution was present in 82% of the samples (L3 and adults) including all post-treatment samples. Moreover, E198V, E198K and potentially E198I, and E198Stop were identified in a few samples.

Conclusions

To our knowledge, this is the first report of E198L in BZ resistantH. contortusand the second where this is the predominant genotype associated with resistance in any strongyle species. Since this variant cannot be quantified using pyrosequencing, the results highlight important limitations in the general applicability of pyrosequencing to quantify BZ resistance genotypes.
Investigating psychometric properties of the Thai version of the Zarit Burden Interview using rasch model and confirmatory factor analysis
Authors: Pinyopornpanish Kanokporn , Pinyopornpanish Manee , Wongpakaran Nahathai , Wongpakaran Tinakon , Soontornpun Atiwat , Kuntawong Pimolpun
Published: March 2020

Objective

The Zarit Burden Interview (ZBI) has been widely used to assess caregiver burden. Few research papers have investigated the Thai version of the ZBI. The study aimed to examine the psychometric properties of the Thai version of both the full length (ZBI-22) and short versions (ZBI-12) using Rasch analysis and confirmatory factor analysis among a sample of Alzheimer’s disease caregivers.

Results

The ZBI-22 fitted the Rasch measurement model regarding unidimensionality but not for ZBI-12. Five items from ZBI-22, and 2 items from ZBI-12 were shown to be misfitting items. Half of ZBI items were shown to be disordered category or threshold, and were locally dependent. CFA revealed three-factor and four-factor fitted the data the best for ZBI-22 and ZBI-12, respectively. Reliability was good for both forms of the ZBI (α = 0.86–0.92). Significant correlations were found with caregiver’s perceived stress, anxiety/depression, pain and mobility but not with self-care and usual activity (p > 0.05), indicating convergent and discriminant validity. To conclude, the Thai version ZBI-22, but not ZBI-12, supported the reliability and unidimensional scale among Alzheimer’s disease caregivers. Some misfitting items of the ZBI undermined the unidimensionality of the scale, and need revision.
The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease
Authors:   the Synaptic Health Endpoints Working Group, Colom-Cadena Martí , Spires-Jones Tara , Zetterberg Henrik , Blennow Kaj , Caggiano Anthony , DeKosky Steven T. , Fillit Howard , Harrison John E. , Schneider Lon S. , Scheltens Phillip , de Haan Willem , Grundman Michael , van Dyck Christopher H. , Izzo Nicholas J. , Catalano Susan M.
Published: March 2020

Background

Synapse damage and loss are fundamental to the pathophysiology of Alzheimer’s disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss.

The key points of this review include the following:

Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.

Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.

Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.

Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.

The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD.

Conclusion

A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes.
The free-living flatworm Macrostomum lignano
Authors: Wudarski Jakub , Egger Bernhard , Ramm Steven A. , Schärer Lukas , Ladurner Peter , Zadesenets Kira S. , Rubtsov Nikolay B. , Mouton Stijn , Berezikov Eugene
Published: March 2020

Macrostomum lignano is a free-living flatworm that is emerging as an attractive experimental animal for research on a broad range of biological questions. One feature setting it apart from other flatworms is the successful establishment of transgenesis methods, facilitated by a steady supply of eggs in the form of single-cell zygotes that can be readily manipulated. This, in combination with the transparency of the animal and its small size, creates practical advantages for imaging and fluorescence-activated cell sorting in studies related to stem cell biology and regeneration. M. lignano can regenerate most of its body parts, including the germline, thanks to the neoblasts, which represent the flatworm stem cell system. Interestingly, neoblasts seem to have a high capacity of cellular maintenance, as M. lignano can survive up to 210 Gy of γ-irradiation, and partially offset the negative consequence of ageing. As a non-self-fertilizing simultaneous hermaphrodite that reproduces in a sexual manner, M. lignano is also used to study sexual selection and other evolutionary aspects of sexual reproduction. Work over the past several years has led to the development of molecular resources and tools, including high-quality genome and transcriptome assemblies, transcriptional profiling of the germline and somatic neoblasts, gene knockdown, and in situ hybridization. The increasingly detailed characterization of this animal has also resulted in novel research questions, such as bio-adhesion based on its adhesion-release glands and genome evolution due to its recent whole-genome duplication.
Transpulmonary thermodilution detects rapid and reversible increases in lung water induced by positive end-expiratory pressure in acute respiratory distress syndrome
Authors: Gavelli Francesco , Teboul Jean-Louis , Azzolina Danila , Beurton Alexandra , Taccheri Temistocle , Adda Imane , Lai Christopher , Avanzi Gian Carlo , Monnet Xavier
Published: March 2020

Purpose

It has been suggested that, by recruiting lung regions and enlarging the distribution volume of the cold indicator, increasing the positive end-expiratory pressure (PEEP) may lead to an artefactual overestimation of extravascular lung water (EVLW) by transpulmonary thermodilution (TPTD).

Methods

In 60 ARDS patients, we measured EVLW (PiCCO2 device) at a PEEP level set to reach a plateau pressure of 30 cmH2O (HighPEEPstart) and 15 and 45 min after decreasing PEEP to 5 cmH2O (LowPEEP15′ and LowPEEP45′, respectively). Then, we increased PEEP back to the baseline level (HighPEEPend). Between HighPEEPstart and LowPEEP15′, we estimated the degree of lung derecruitment either by measuring changes in the compliance of the respiratory system (Crs) in the whole population, or by measuring the lung derecruited volume in 30 patients. We defined patients with a large derecruitment from the other ones as patients in whom the Crs changes and the measured derecruited volume were larger than the median of these variables observed in the whole population.

Results

Reducing PEEP from HighPEEPstart (14 ± 2 cmH2O) to LowPEEP15′ significantly decreased EVLW from 20 ± 4 to 18 ± 4 mL/kg, central venous pressure (CVP) from 15 ± 4 to 12 ± 4 mmHg, the arterial oxygen tension over inspired oxygen fraction (PaO2/FiO2) ratio from 184 ± 76 to 150 ± 69 mmHg and lung volume by 144 [68–420] mL. The EVLW decrease was similar in “large derecruiters” and the other patients. When PEEP was re-increased to HighPEEPend, CVP, PaO2/FiO2 and EVLW significantly re-increased. At linear mixed effect model, EVLW changes were significantly determined only by changes in PEEP and CVP (p < 0.001 and p = 0.03, respectively, n = 60). When the same analysis was performed by estimating recruitment according to lung volume changes (n = 30), CVP remained significantly associated to the changes in EVLW (p < 0.001).

Conclusions

In ARDS patients, changing the PEEP level induced parallel, small and reversible changes in EVLW. These changes were not due to an artefact of the TPTD technique and were likely due to the PEEP-induced changes in CVP, which is the backward pressure of the lung lymphatic drainage.

Trial registration ID RCB: 2015-A01654-45. Registered 23 October 2015
Short- and long-term renal outcomes following severe rhabdomyolysis: a French multicenter retrospective study of 387 patients
Authors:   on behalf of the French Intensive Care Renal Network (F.I.R.N), Candela Nelly , Silva Stein , Georges Bernard , Cartery Claire , Robert Thomas , Moussi-Frances Julie , Rondeau Eric , Rebibou Jean-Michel , Lavayssiere Laurence , Belliere Julie , Krummel Thierry , Lebas Céline , Cointault Olivier , Sallee Marion , Faguer Stanislas
Published: March 2020

Background

Rhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic kidney disease (CKD) transition remain poorly described.

Methods

This multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary end-points included the incidence of AKI to CKD transition.

Results

Among the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2–3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m2in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission.

Conclusions

Severe rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2–3 AKI. The long-term renal decline is correlated to serum myoglobin at admission.
On the spectrum of the weighted p-Laplacian under the Ricci-harmonic flow
Authors: Abolarinwa Abimbola , Edeki Sunday O. , Ehigie Julius O.
Published: March 2020

This paper studies the behaviour of the spectrum of the weightedp-Laplacian on a complete Riemannian manifold evolving by the Ricci-harmonic flow. Precisely, the first eigenvalue diverges in a finite time along this flow. It is further shown that the same divergence result holds on gradient shrinking and steady almost Ricci-harmonic solitons under the condition that the soliton function is nonnegative and superharmonic. We also continue the program in (Abolarinwa, Adebimpe and Bakare in J. Ineq. Appl. 2019:10, 2019) to the case of volume-preserving Ricci-harmonic flow.