bluuebunny/crossref_metadata_2025 huggingface dataset:
The center of olfactory bulb‐seeded α‐synucleinopathy is the limbic system and the ensuing pathology is higher in male than in female mice
Authors: Mason Daniel M. , Wang Yaqin , Bhatia Tarun N. , Miner Kristin M. , Trbojevic Sara A. , Stolz John F. , Luk Kelvin C. , Leak Rehana K.
Published: March 2019

At early disease stages, Lewy body disorders are characterized by limbic vs. brainstem α‐synucleinopathy, but most preclinical studies have focused solely on the nigrostriatal pathway. Furthermore, male gender and advanced age are two major risk factors for this family of conditions, but their influence on the topographical extents of α‐synucleinopathy and the degree of cell loss are uncertain. To fill these gaps, we infused α‐synuclein fibrils in the olfactory bulb/anterior olfactory nucleus complex—one of the earliest and most frequently affected brain regions in Lewy body disorders—in 3‐month‐old female and male mice and in 11‐month‐old male mice. After 6 months, we observed that α‐synucleinopathy did not expand significantly beyond the limbic connectome in the 9‐month‐old male and female mice or in the 17‐month‐old male mice. However, the 9‐month‐old male mice had developed greater α‐synucleinopathy, smell impairment and cell loss than age‐matched females. By 10.5 months post‐infusion, fibril treatment hastened mortality in the 21.5‐month‐old males, but the inclusions remained centered in the limbic system in the survivors. Although fibril infusions reduced the number of cells expressing tyrosine hydroxylase in the substantia nigra of young males at 6 months post‐infusion, this was not attributable to true cell death. Furthermore, mesencephalic α‐synucleinopathy, if present, was centered in mesolimbic circuits (ventral tegmental area/accumbens) rather than within strict boundaries of the nigral pars compacta, which were defined here by tyrosine hydroxylase immunolabel. Nonprimate models cannot be expected to faithfully recapitulate human Lewy body disorders, but our murine model seems reasonably suited to (i) capture some aspects of Stage IIb of Lewy body disorders, which displays a heavier limbic than brainstem component compared to incipient Parkinson’s disease; and (ii) leverage sex differences and the acceleration of mortality following induction of olfactory α‐synucleinopathy.
Use of Delphian lymph node metastasis to predict central and lateral involvement in papillary thyroid carcinoma: A systematic review and meta‐analysis
Authors: Huang Jiapeng , Sun Wei , Zhang Hao , Zhang Ping , Wang Zhihong , Dong Wenwu , He Liang , Zhang Ting
Published: March 2019

Objective

Whether Delphian lymph node (DLN) metastasis is a reliable predictor of widespread lymph node metastasis in papillary thyroid carcinoma (PTC) remains controversial. This meta‐analysis investigated the value of DLN metastasis for predicting central and lateral involvement in PTC.

Design and Methods

A literature search using the PubMed, SCIE and the Chinese National Knowledge Infrastructure (CNKI) databases was conducted. Two reviewers independently extracted data and evaluated the studies for inclusion. Fixed‐effects and random‐effects models were used to analyse the data based on their heterogeneity. A sensitivity analysis was performed, and publication bias was assessed using Begg's funnel plot and Egger's linear regression test.

Results

Data from 10 studies were analysed. The risk of central lymph node (CLN) metastasis was significantly higher in the DLN‐positive group than in the DLN‐negative group (OR = 9.05, 95% CI: 5.13‐15.99) with moderate heterogeneity (P = 0.022, I2 = 53.5%). The risk of lateral lymph node (LLN) metastasis was significantly higher in the DLN‐positive group than in the negative group (OR = 10.88, 95% CI: 7.60‐15.58), with low heterogeneity (P = 0.603, I2 = 0.0%). Sensitivity analysis indicated that the results were stable and credible, and no publication bias was found.

Conclusions

Delphian lymph node metastasis is valuable for predicting central and lateral compartment involvement in patients with PTC. The DLN of PTC patients should be dissected intraoperatively and sent for frozen section consultation. If the result is positive, the CLNs should be thoroughly dissected and the LLNs should be further evaluated.
Hand eczema patients’ knowledge of skin protection following a guided talk—A retrospective study with a follow‐up questionnaire
Authors: Topal Yasemin , Agner Tove , van der Heiden Janique , Ebbehøj Niels E. , Clemmensen Kim K. B.
Published: March 2019

Background

Several studies have assessed the effect of patient education regarding hand eczema (HE) severity and quality of life. Few studies, however, have evaluated patients’ knowledge.

Objectives

To examine knowledge of skin protection in HE patients following a guided talk, and to identify variables associated with knowledge.

Methods

HE patients referred to the outpatient dermatological clinic, Bispebjerg Hospital, between January 2013 and July 2014 were offered a guided talk on HE prevention. HE severity and the Dermatology Life Quality Index (DLQI) score were assessed. A questionnaire comprising 10 questions about skin protection was sent 1 to 2.5 years later.

Results

One hundred and twenty patients responded to the questionnaire (response 53.5%). The mean percentage of correct answers was 74.7%. Sixty per cent responded correctly to at least eight questions. Male sex, older age and education for >5 years were associated with a low level of knowledge. Education for 3 to 4 years (P = 0.045) was associated with a higher level of knowledge. No significant impact of previous/current atopic dermatitis, HE severity or previous information on skin protection was found with respect to level of knowledge.

Conclusions

Females and patients with education for 3 to 4 years showed the highest level of knowledge, whereas males, older patients and patients with education for >5 years should be brought more into focus in skin protection programmes.
Induction of neutrophil extracellular traps during tissue injury: Involvement of STING and Toll‐like receptor 9 pathways
Authors: Liu Li , Mao Ye , Xu Bocheng , Zhang Xiangxian , Fang Chunju , Ma Yu , Men Ke , Qi Xiaorong , Yi Tao , Wei Yuquan , Wei Xiawei
Published: March 2019

Objectives

Neutrophils are thought to release neutrophil extracellular traps (NETs) to form in response to exogenous bacteria, viruses and other pathogens. However, the mechanisms underlying NET formation during sterile inflammation are still unclear. In this study, we would like to identify neutrophil extracellular traps formation during sterile inflammation and tissue injury and associated pathways and its mechanism.

Materials and methods

We identified different injuries such as chemical‐induced and trauma‐induced formation of NETs and investigated mechanism of the formation of NETs in vitro and in vivo during the treatment of mtDNA.

Results

Here, we find the release of mitochondrial DNA (mtDNA) and oxidized mtDNA in acute peripheral tissue trauma models or other chemically induced lung injury, and moreover, endogenous mtDNA and oxidized mtDNA induce the formation of NETs and sterile inflammation. Oxidized mtDNA is a more potent inducer of NETs. Mitochondrial DNA activates neutrophils via cyclic GMP‐AMP synthase (cGAS)‐STING and the Toll‐like receptor 9 (TLR9) pathways and increases the production of neutrophil elastase and extracellular neutrophil‐derived DNA in NETs. Mitochondrial DNA also increases the production of reactive oxygen species (ROS) and expression of the NET‐associated proteins Rac 2 and peptidylarginine deiminase 4 (PAD4).

Conclusions

Altogether, these findings highlight that endogenous mitochondrial DNA inducted NETs formation and subsequent sterile inflammation and the mechanism associated with NET formation.
Primary cutaneous diffuse large B‐cell lymphoma, NOS and leg type: Clinical, morphologic and prognostic differences
Authors: Felcht Moritz , Klemke Claus‐Detlev , Nicolay Jan Peter , Weiss Christel , Assaf Chalid , Wobser Marion , Schlaak Max , Hillen Uwe , Moritz Rose , Tantcheva‐Poor Iliana , Nashan Dorothee , Beyer Marc , Dippel Edgar , Müller Cornelia Sigrid Lissi , Sachse Michael Max , Meiss Frank , Géraud Cyrill , Marx Alexander , Goerdt Sergij , Geissinger Eva , Kempf Werner
Published: March 2019

Background and objectives

Primary cutaneous diffuse large B‐cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl‐2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT) and help to assess the clinical course/prognosis.

Patients and methods

Bcl‐2– PCLBCL/NOS) cases (n = 14 were compared with Bcl‐2+ PCLBCL/LT cases (n = 29).

Results

PCLBCL/NOS patients were younger, predominantly male and had better survival rates than patients with PCLBCL/LT. Patients with PCLBCL/NOS presented more often with larger plaques limited to one or two contiguous body regions, whereas PCLBCL/LT cases often presented with disseminated lesions. Neoplastic cells had a higher proliferation rate (Ki67) in PCLBCL/LT patients. The tumor microenvironment of PCLBCL/NOS had a more prominent CD3+ infiltrate. Overall survival data for the whole cohort (n = 37) revealed that female gender and Bcl‐2 expression correlated with a worse survival rate. Bcl‐6 expression and centroblastic subtype correlated with better outcomes. None of the other markers studied (e.g. GCB/non‐GCB subtype) correlated with survival rate.

Conclusions

PCLBCL/NOS and PCLBCL/LT differ in their clinical behavior and outcomes. Bcl‐2 still seems to be the best marker for discriminating between these two subgroups. Bcl‐2, female gender and Bcl‐6 represent prognostic markers for PCLBCL.
Take Control: A randomized trial evaluating the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes
Authors: Russell‐Jones David , Dauchy Arnaud , Delgado Elías , Dimitriadis George , Frandsen Hans A. , Popescu Luiza , Schultes Bernd , Strojek Krzysztof , Bonnemaire Mireille , Roborel de Climens Aude , Davies Melanie
Published: March 2019

Aim

To compare the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL (Gla‐300) in people with inadequately controlled type 2 diabetes.

Methods

Take Control (EudraCT number: 2015‐001626‐42) was a 24‐week, multi‐national, open‐label, controlled, two‐arm, parallel‐group study in insulin‐naïve and pre‐treated participants, randomized 1:1 to a self‐ or physician‐managed titration of Gla‐300. The fasting self‐monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant‐reported outcomes (PROs).

Results

At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self‐ and physician‐managed groups, respectively, with an LS mean difference of −0.13% [95% confidence interval −0.2619 to −0.0004] (–1.4 mmol/mol [–2.863 to –0.004]), demonstrating non‐inferiority (P < 0.0001) and superiority (P = 0.0247) of self‐ versus physician‐managed titration. Significantly more of the self‐ than physician‐managed group achieved SMPG target without hypoglycaemia (67% vs 58%; P = 0.0187). Overall, hypoglycaemia incidence was similar in each group. No safety concerns were reported. In both groups, similar PRO improvements were observed for distress related to diabetes disease burden and for confidence in diabetes self‐management, with even more individuals achieving a clinically relevant reduction in emotional burden and fewer individuals with high emotional burden in the self‐managed group.

Conclusions

Self‐managed titration of Gla‐300 was superior to physician‐managed titration in terms of HbA1c reduction, accompanied by similar total PRO scores, with a clinically relevant reduction in emotional burden, and similar hypoglycaemia frequency.
Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials
Authors: Verma Subodh , Bain Stephen C. , Monk Fries Tea , Mazer C. David , Nauck Michael A. , Pratley Richard E. , Rasmussen Søren , Saevereid Hans A. , Zinman Bernard , Buse John B.
Published: March 2019

Cardiovascular risk reduction with liraglutide and semaglutide in patients with type 2 diabetes was demonstrated in the LEADER (ClinicalTrials.gov: NCT01179048) and SUSTAIN 6 (ClinicalTrials.gov: NCT01720446) cardiovascular outcome trials. This post hoc analysis assessed the impact of diabetes duration (<5, 5 to <15, 15 to <25 and ≥25 years at baseline) on cardiorenal efficacy of these human glucagon‐like peptide‐1 analogues using a Cox proportional hazards model. Proportions of patients in the LEADER trial across diabetes duration strata were 15% (<5 years, n = 1377), 50% (5 to <15 years, n = 4692), 27% (15 to <25 years, n = 2504) and 8% (≥25 years, n = 748); corresponding proportions in the SUSTAIN‐6 trial were 13% (<5 years, n = 422), 48% (5 to <15 years, n = 1582), 30% (15 to <25 years, n = 977) and 10% (≥25 years, n = 316). Overall, longer diabetes duration was associated with higher age; higher prevalence of females; history of ischaemic stroke, peripheral arterial disease and insulin use; and inferior renal function. There was an increased frequency of major adverse cardiovascular events (MACE), expanded MACE and nephropathy events with increasing diabetes duration. Liraglutide and semaglutide consistently reduced the risk of cardiorenal outcomes across categories of diabetes duration (P‐interaction was not significant for all endpoints analysed).
Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7)
Authors: Pratley Richard E. , Emerson Scott S. , Franek Edward , Gilbert Matthew P. , Marso Steven P. , McGuire Darren K. , Pieber Thomas R. , Zinman Bernard , Hansen Charlotte T. , Hansen Melissa V. , Mark Thomas , Moses Alan C. , Buse John B. ,   on behalf of the DEVOTE Study Group
Published: March 2019

Aims

The aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older.

Materials and methods

A total of 7637 patients in the DEVOTE trial, a treat‐to‐target, randomized, double‐blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50‐64 years, n = 3682; 65‐74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all‐cause mortality, severe hypoglycaemia and serious adverse events (SAEs).

Results

Patients with increasing age had higher risks of CV death, all‐cause mortality and SAEs, and there were non‐significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all‐cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non‐significant interactions between treatment and age with regard to these outcomes.

Conclusions

There were higher risks of CV death, all‐cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all‐cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all‐cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.
The spectrum of neuroimaging findings in febrile infection‐related epilepsy syndrome (FIRES): A literature review
Authors: Culleton Sinead , Talenti Giacomo , Kaliakatsos Marios , Pujar Suresh , D'Arco Felice
Published: March 2019

Febrile infection‐related epilepsy syndrome (FIRES) is a rare severe epileptic syndrome occurring in previously healthy children and characterized by refractory status epilepticus (SE) following a febrile illness. Brain imaging findings in affected patients have been reported in few case series and some case reports. This article is a comprehensive review of the magnetic resonance imaging (MRI)characteristics in all reported patients with a diagnosis ofFIRES, describing the findings in the acute and chronic phases of the disease, and discussing possible pathogenesis and radiologic differential diagnoses. Most of the patients had normal brain scans in the acute phase (61%) and about 25% of the patients reported in literature had abnormalities in the temporal lobes. Changes in the basal ganglia and rarely in thalami or brainstem have also been described, as well as diffuse cerebral edema in a minority of patients during the acute phase. The chronic phase of the disease was characterized by atrophic changes and evidence of mesiotemporal sclerosis. An understanding of theseMRIabnormalities is necessary to support the diagnosis ofFIRESand exclude mimics.
Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective
Authors: Dogan Muhammed Fatih , Yildiz Oguzhan , Arslan Seyfullah Oktay , Ulusoy Kemal Gokhan
Published: March 2019

Potassium (K+) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2‐activated K+ channels (BKCa), voltage‐dependent K+ channels (KV), ATP‐sensitive K+ channels (KATP), inward rectifier K+ channels (Kir), and tandem two‐pore K+ channels (K2P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.
Woody vegetation dynamics in the tropical and subtropical Andes from 2001 to 2014: Satellite image interpretation and expert validation
Authors: Aide T. Mitchell , Grau H. Ricardo , Graesser Jordan , Andrade‐Nuñez Maria Jose , Aráoz Ezequiel , Barros Ana P. , Campos‐Cerqueira Marconi , Chacon‐Moreno Eulogio , Cuesta Francisco , Espinoza Raul , Peralvo Manuel , Polk Molly H. , Rueda Ximena , Sanchez Adriana , Young Kenneth R. , Zarbá Lucía , Zimmerer Karl S.
Published: March 2019

The interactions between climate and land‐use change are dictating the distribution of flora and fauna and reshuffling biotic community composition around the world. Tropical mountains are particularly sensitive because they often have a high human population density, a long history of agriculture, range‐restricted species, and high‐beta diversity due to a steep elevation gradient. Here we evaluated the change in distribution of woody vegetation in the tropical Andes of South America for the period 2001–2014. For the analyses we created annual land‐cover/land‐use maps using MODIS satellite data at 250 m pixel resolution, calculated the cover of woody vegetation (trees and shrubs) in 9,274 hexagons of 115.47 km2, and then determined if there was a statistically significant (p < 0.05) 14 year linear trend (positive—forest gain, negative—forest loss) within each hexagon. Of the 1,308 hexagons with significant trends, 36.6% (n = 479) lost forests and 63.4% (n = 829) gained forests. We estimated an overall net gain of ~500,000 ha in woody vegetation. Forest loss dominated the 1,000–1,499 m elevation zone and forest gain dominated above 1,500 m. The most important transitions were forest loss at lower elevations for pastures and croplands, forest gain in abandoned pastures and cropland in mid‐elevation areas, and shrub encroachment into highland grasslands. Expert validation confirmed the observed trends, but some areas of apparent forest gain were associated with new shade coffee, pine, or eucalypt plantations. In addition, after controlling for elevation and country, forest gain was associated with a decline in the rural population. Although we document an overall gain in forest cover, the recent reversal of forest gains in Colombia demonstrates that these coupled natural‐human systems are highly dynamic and there is an urgent need of a regional real‐time land‐use, biodiversity, and ecosystem services monitoring network.
Automated FRET quantification shows distinct subcellular ERK activation kinetics in response to graded EGFR signaling in Drosophila
Authors: Ogura Yosuke , Sami Mustafa M. , Wada Housei , Hayashi Shigeo
Published: March 2019

Threshold responses to an activity gradient allow a single signaling pathway to yield multiple outcomes. Extracellular signal‐regulated kinase (ERK) is one such signal, which couples receptor tyrosine kinase signaling with multiple cellular responses in various developmental processes. Recent advances in the development of fluorescent biosensors for live imaging have enabled the signaling activities accompanying embryonic development to be monitored in real time. Here, we used an automated computational program to quantify the signals of a fluorescence resonance energy transfer (FRET) reporter for activated ERK, and we used this system to monitor the spatio‐temporal dynamics of ERK during neuroectoderm patterning in Drosophila embryos. We found that the cytoplasmic and nuclear ERK activity gradients show distinct kinetics in response to epidermal growth factor receptor activation. The ERK activation patterns implied that the cytoplasmic ERK activity is modulated into a threshold response in the nucleus.
Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages
Authors: Takemasu Shinya , Ito Masaaki , Morioka Shin , Nigorikawa Kiyomi , Kofuji Satoshi , Takasuga Shunsuke , Eguchi Satoshi , Nakanishi Hiroki , Matsuoka Isao , Sasaki Junko , Sasaki Takehiko , Hazeki Kaoru
Published: March 2019

Lysophosphatidylinositol‐acyltransferase‐1 (LPIAT1) specifically catalyzes the transfer of arachidonoyl‐CoA to lysophosphoinositides. LPIAT−/− mice have been shown to have severe defects in the brain and liver; however, the exact molecular mechanisms behind these conditions are not well understood. As immune cells have been implicated in liver inflammation based on disfunction of LPIAT1, we generated Raw264.7 macrophages deficient in LPIAT1, using shRNA and CRISPR/Cas9. The amount of C38:4 species in phosphoinositides, especially in PtdInsP2, was remarkably decreased in these cells. Unlike in wild‐type cells, LPIAT1‐deficient cells showed prolonged oscillations of intracellular Ca2+ upon UDP stimulation, which is known to activate phospholipase Cβ through the Gq‐coupled P2Y6 receptor, even in the absence of extracellular Ca2+. It is speculated that the prolonged Ca2+ response may be relevant to the increased risk of liver inflammation induced by LPIAT1 disfunction.
Metabolic regulation of inflammasomes in inflammation
Authors: Yang Qiuli , Liu Ruichen , Yu Qing , Bi Yujing , Liu Guangwei
Published: March 2019

Summary

Inflammasome activation and subsequent inflammatory cytokine secretion are essential for innate immune defence against multiple stimuli and are regarded as a link to adaptive immune responses. Dysfunction of inflammasome activation has been discovered at the onset or progression of infectious diseases, autoimmune diseases and cancer, all of which are also associated with metabolic factors. Furthermore, many studies concerning the metabolic regulation of inflammasome activation have emerged in recent years, especially regarding the activity of the NLRP3 inflammasome under metabolic reprogramming. In this review, we discuss the molecular mechanisms of the interactions between metabolic pathways and inflammasome activation, which exerts further important effects on various diseases.
Population growth potential of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) on tomato, potato, and eggplant
Authors: Kanle Satishchandra Nitin , Chakravarthy Akshay Kumar , Özgökçe Mehmet Salih , Atlihan Remzi
Published: March 2019

The influence of host plant on population dynamics of an invasive pest, Tuta absoluta was studied on three economically important solanaceous crops. Experiments were conducted in laboratory (29 ± 0.5°C, 75 ± 5% RH and a photoperiod of 14:10 hr [L:D]) using tomato (Solanum lycopersicum L.), potato (Solanum tuberosum L.) and eggplant (Solanum melongena L.). Results indicated that intrinsic rate of increase (r), finite rate of increase (λ) and net reproductive rate (R0) were higher, and mean generation time (T) was the shortest on tomato. Results suggested that T. absoluta developed on all the three plants, and tomato plant was most preferred one. Results suggested that T. absoluta has a potential to become a serious pest on potato and even on eggplant under favourable conditions. We used the life tables of 0.025th and 0.975th percentiles of bootstraps to project the uncertainty of population growth, a new concept.
Identification and functional characterization of Histone‐like DNA‐binding protein in Nocardia seriolae (NsHLP) involved in cell apoptosis
Authors: Wang Wenji , Chen Jianlin , Liao Baoshan , Xia Liqun , Hou Suying , Wang Zhiwen , Lu Yishan
Published: March 2019

Nocardia seriolae, a facultative intracellular bacterium, is the main pathogen of fish nocardiosis. Bioinformatic analysis showed that the histone‐like DNA‐binding protein (HLP) gene of N. seriolae (nshlp) encoded a secreted protein and might target the mitochondria in the host cell. To further study the preliminary function of HLP in N. seriolae (NsHLP), the gene cloning, extracellular products identification, subcellular localization, overexpression and apoptosis detection assay were carried out in this study. Mass spectrometry analysis of the extracellular products from N. seriolae showed that NsHLP was a secreted protein. Subcellular localization of HLP‐GFP fusion proteins mainly assembled in the nucleus, which indicated that the NsHLP was co‐located with the nucleus rather than mitochondria in fathead minnow (FHM) cells. Notably, the expression of NsHLP had changed the distribution of mitochondria into lumps in the FHM cell. In addition, apoptotic features were found in the transfected FHM cells by overexpression of NsHLP. Quantitative assays of mitochondrial membrane potential value, caspase‐3 activity and pro‐apoptotic genes mRNA (Bad, Bid and Bax) expression level demonstrated that the cell apoptosis was induced in the transfected FHM cells. All the results presented in this study provided insight on the function of NsHLP, which suggested that it may participate in the cell apoptosis regulation and play an important role in the pathogenesis of N. seriolae.
First report of isolation and complete genome of Vibrio rotiferianus strain SSVR1601 from cage‐cultured black rockfish (Sebastes schlegelii) associated with skin ulcer
Authors: Zhang Zheng , Yu Yong‐xiang , Jiang Yong , Wang Yin‐geng , Liao Mei‐jie , Rong Xiao‐jun , Wang Kai , Zhang Hao , Chen Jing
Published: March 2019

Vibrio rotiferianus is an important marine pathogen of various aquatic organisms and can be found widely distributed in the marine environment. To further characterize this pathogen, the pathogenic properties and genome of V. rotiferianus SSVR1601 isolated from Sebastes schlegelii with skin ulcer were analysed. SSVR1601 was shown to be short rod‐shaped cell with a single polar flagellum. Different degrees of pathological changes in fish kidney, intestine, gills and liver were observed after SSVR1601 challenge. The SSVR1601 genome consists of two chromosomes and two plasmids with a total of 5,717,113 bp, 42.04%–44.93% GC content, 5,269 predicted CDSs, 134 tRNAs and 40 rRNAs. The common virulence factors including OMPs, haemolysin, flagellin, DNase, entF, algU, tcpI, acfB and rfaD were found in strain SSVR1601. Furthermore, factors responsible for iron uptake (fur, fepC and ccmC) and types II, IV and VI secretion systems were detected, which are likely responsible for the pathogenicity of SSVR1601. The antimicrobial resistance genes, bacA, tet34 and norM, were detected based on Antibiotic Resistance Genes Database. The phylogenetic analysis revealed SSVR1601 to be most closely related to V. rotiferianus strains CAIM577 and B64D1.
Genetic parameters for resistance against Vibrio anguillarum in turbot Scophthalmus maximus
Authors: Wang Xin‐An , Ma Ai‐Jun
Published: March 2019

Genetic parameters for resistance to Vibrio anguillarum in Scophthalmus maximus were estimated using three different statistical models. Data were recorded from an experimental infection performed on 2,400 individuals from 30 full‐sib groups. Cross‐sectional linear model and cross‐sectional threshold probit model were used to analyse the test‐period survival; the cross‐sectional threshold logit models were used to analyse the test‐day survival. The heritability values estimated by cross‐sectional linear model (CSL), cross‐sectional threshold (probit) model (THRp) and cross‐sectional threshold (logit) model (THRl) were 0.202 ± 0.101, 0.296 ± 0.168 and 0.110 ± 0.023, respectively. The correlation coefficients between the full‐sib families’ estimated breeding values (EBVs) based on these three models were over 0.993. An almost identical ranking of families was generated using any of these models. Accuracy of selection using CSL, THRp and THRl models was 0.783, 0.789 and 0.801, respectively. Accuracy of selection based on the THRl model was higher than that based on CSL and THRp models.
Leech (Myzobdella lugubris) infestations in largemouth bass (Micropterus salmoides) in Back Bay, Virginia, USA
Authors: Pomposini Amanda , Blubaugh Jonathan , Boyce Robert Chad , Gauthier David T.
Published: March 2019

Back Bay is an oligohaline, coastal bay in southeast Virginia, USA. Since 2004, leeches have been observed in the oral cavities of largemouth bass (Micropterus salmoides) in this body of water. Leeches (Myzobdella lugubris) have previously been documented in the oral cavities of largemouth bass in the Currituck Sound, which is confluent with Back Bay on its southern border. Supplemental stocking of largemouth bass in Back Bay since 2009 has resulted in an increasing population; however, concern exists that leech infestation may be negatively affecting health of larger fish, which are still less abundant than expected. Despite the wide distribution of this leech, there is little available literature regarding its health impacts on hosts. In this study, we examine potential impacts of oral leech infestations on stress markers and haematological parameters of largemouth bass in Back Bay. No significant changes in plasma glucose or cortisol were observed between leech‐infested and uninfested fish, and haematological parameters were not significantly different between the groups. Further, there was no evidence of systemic infections associated with leech infestation.
Does Ralstonia eutropha, rich in poly‐β hydroxybutyrate (PHB), protect blue mussel larvae against pathogenic vibrios?
Authors: Van Hung Nguyen , Bossier Peter , Hong Nguyen Thi X. , Ludeseve Christine , Garcia‐Gonzalez Linsey , Nevejan Nancy , De Schryver Peter
Published: March 2019

The natural amorphous polymer poly‐β‐hydroxybutyrate (PHB‐A: lyophilized Ralstonia eutropha containing 75% PHB) was used as a biological agent to control bacterial pathogens of blue mussel (Mytilus edulis) larvae. The larvae were supplied with PHB‐A at a concentration of 1 or 10 mg/L for 6 or 24 hr, followed by exposure to either the rifampicin‐resistant pathogen Vibrio splendidus or Vibrio coralliilyticus at a concentration of 105 CFU/ml. Larvae pretreated 6 hr with PHB‐A (1 mg/L) survived a Vibrio challenge better relative to 24 hr pretreatment. After 96 hr of pathogen exposure, the survival of PHB‐A‐treated mussel larvae was 1.41‐ and 1.76‐fold higher than the non‐treated larvae when challenged with V. splendidus and V. coralliilyticus, respectively. Growth inhibition of the two pathogens at four concentrations of the monomer β‐HB (1, 5, 25 and 125 mM) was tested in vitro in LB35 medium, buffered at two different pH values (pH 7 and pH 8). The highest concentration of 125 mM significantly inhibited the pathogen growth in comparison to the lower levels. The effect of β‐HB on the production of virulence factors in the tested pathogenic Vibrios revealed a variable pattern of responses.
Genotypic and phenotypic characterization of Edwardsiella isolates from different fish species and geographical areas in Asia: Implications for vaccine development
Authors: Dubey Saurabh , Maiti Biswajit , Kim Sung‐Hyun , Sivadasan Sangeetha Madambithara , Kannimuthu Dhamotharan , Pandey Pramod Kumar , Girisha Shivani Kallappa , Mutoloki Stephen , Chen Shih‐Chu , Evensen Øystein , Karunasagar Indrani , Munang´andu Hetron Mweemba
Published: March 2019

The genus Edwardsiella is one of the major causes of fish diseases globally. Herein, we examined 37 isolates from ten different fish species from India, South Korea and Taiwan to gain insight into their phenotypic and genotypic properties, of which 30 were characterized as E. tarda with phenotypic homology estimated at 85.71% based on API‐20E biochemical tests. Genotyping using 16S rRNA put all isolates together with E. anguillarum, E. hoshinae, E. tarda, E. piscicida and E. ictaluri reference strains in a monophyletic group. In contrast, the gyrB phylogenetic tree clearly separated E. ictaluri, E. tarda and E. hoshinae reference strains from our isolates and put our isolates into two groups with group I being homologous with the E. anguillarum reference strain while group II was homologous with the E. piscicida reference strain. Hence, our findings point to E. piscicida and E. anguillarum as species infecting different fish species in Asia. Homology of the ompW protein suggested that strains with broad protective coverage could be identified as vaccine candidates. This study underscores the importance of combining genotyping with phenotyping for valid species classification. In addition, it accentuates the importance of phylogenetic comparison of bacterial antigens for identification of potential vaccine candidates.
Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome
Authors: Halmos Emma P , Gibson Peter R
Published: March 2019

Since its first trial showing evidence of efficacy for managing symptoms of irritable bowel syndrome, the fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has been gaining popularity but not without criticism. Application of the diet has changed from a rigid list of “allowed” and “not allowed” foods to a structured program of initial FODMAP restriction followed by food reintroduction and finally personalization so that patients are empowered to adjust their diet themselves to achieve good predictability of symptoms. Safety concerns of the diet have centered around its initial elimination leading to compromise of nutritional and psychological health, but careful patient assessment and management, preferably through a FODMAP‐trained dietitian, will reduce the risk of such negative health outcomes. Most negative attention for the FODMAP diet has been the notion that it will ruin the microbiota. Controlled studies have indicated that reducing FODMAP intake has no effects on bacterial diversity but will reduce total bacterial abundance, and higher FODMAP intakes will increase health‐promoting bacteria, supporting the concept of the full FODMAP program, including attaining a minimal “maintenance” level of FODMAP restriction. This review addresses all these concerns in detail and how to overcome them, including the use of a “FODMAP‐gentle” diet, describing restriction of a select few foods very concentrated in FODMAPs. This version of the diet is commonly applied in practice by experienced FODMAP‐trained dietitians but is not clearly described in literature. Careful direction and assessment of response or nonresponse will decrease the risks of over‐restriction and under‐restriction of diet.
Why Amyloid Is Still a Target for Alzheimer Disease Clinical Trials
Authors: McDade Eric
Published: March 2019

See the response from Eric McDade.
Implementing Advance Care Planning in Acute Hospitals: Leading the Transformation of Norms
Authors: Tan Woan Shin , Car Josip , Lall Priya , Low Chan Kee , Ho Andy Hau Yan
Published: March 2019

BACKGROUND

Despite being simply defined as a process to further one's understanding about future medical care, the process of implementing advance care planning (ACP) within acute hospital settings can be complex.

AIM

We describe different ACP service models adopted in Singapore, and the facilitators for, and barriers to, its effective implementation.

DESIGN

Qualitative focus group study with thematic analysis.

SETTINGS/PARTICIPANTS

We purposefully sampled four stakeholder groups involved in the implementation of ACP. Our sample included 63 participants, 12 physicians, 15 nurses, 24 medical social workers, and 12 ACP coordinators from seven public hospitals and one specialist center.

RESULTS

We describe three different acute‐care models adopted in Singapore, differentiated by leadership approach, target population, delivery process, and job roles. Our results revealed nine themes, organized into four categories, including: (1) hospital culture (curative norms, absence of preference‐supportive culture), (2) organizational priority and leadership (low priority on hospital agenda, inappropriate leadership), (3) goals and distinction (lack of shared purpose and goals, no clear differentiation from existing practices), and (4) work practices (pigeonholing of ACP practice, inappropriate resourcing, accountability and feedback).

CONCLUSION

We learned that to implement ACP effectively in an acute‐care setting, there needs to be a cultural and behavioral transformation, led by committed and empowered leaders. Organizations that can create a shared purpose built on an ethos of honoring patients' preferences, and support this with systematic processes and adequate resourcing, will be more equipped to implement ACP effectively.
Ionized calcium in human cerebrospinal fluid and its influence on intrinsic and synaptic excitability of hippocampal pyramidal neurons in the rat
Authors: Forsberg My , Seth Henrik , Björefeldt Andreas , Lyckenvik Tim , Andersson Mats , Wasling Pontus , Zetterberg Henrik , Hanse Eric
Published: March 2019

It is well‐known that the extracellular concentration of calcium affects neuronal excitability and synaptic transmission. Less is known about the physiological concentration of extracellular calcium in the brain. In electrophysiological brain slice experiments, the artificial cerebrospinal fluid traditionally contains relatively high concentrations of calcium (2‐4 mM) to support synaptic transmission and suppress neuronal excitability. Using an ion‐selective electrode, we determined the fraction of ionized calcium in healthy human cerebrospinal fluid to 1.0 mM of a total concentration of 1.2 mM (86%). Using patch‐clamp and extracellular recordings in the CA1 region in acute slices of rat hippocampus, we then compared the effects of this physiological concentration of calcium with the commonly used 2 mM on neuronal excitability, synaptic transmission, and long‐term potentiation (LTP) to examine the magnitude of changes in this range of extracellular calcium. Increasing the total extracellular calcium concentration from 1.2 to 2 mM decreased spontaneous action potential firing, induced a depolarization of the threshold, and increased the rate of both de‐ and repolarization of the action potential. Evoked synaptic transmission was approximately doubled, with a balanced effect between inhibition and excitation. In 1.2 mM calcium high‐frequency stimulation did not result in any LTP, whereas a prominent LTP was observed at 2 or 4 mM calcium. Surprisingly, this inability to induce LTP persisted during blockade of GABAergic inhibition. In conclusion, an increase from the physiological 1.2 mM to 2 mM calcium in the artificial cerebrospinal fluid has striking effects on neuronal excitability, synaptic transmission, and the induction of LTP.

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Read the Editorial Highlight for this article on page 435.
National survey of uterine rupture in Japan: Annual report of Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2018
Authors: Makino Shintaro , Takeda Satoru , Kondoh Eiji , Kawai Kenta , Takeda Jun , Matsubara Shigeki , Itakura Atsuo , Sago Haruhiko , Tanigaki Shinji , Tanaka Mamoru , Ikeda Tomoaki , Kanayama Naohiro
Published: March 2019

Aim

To clarify the frequency of occurrence of uterine rupture and its prognosis, a nationwide survey was performed.

Methods

Cases of uterine rupture recorded for a period of 5 years were included.

Results

There were 152 cases of uterine rupture with an incidence rate of 0.015%. The scarred uterine rupture cases were found to have a significantly earlier occurrence of uterine ruptures in comparison to the unscarred cases: unscarred 39.0 weeks, cesarean section 37.0 weeks, myomectomy 32 weeks and adenomyomectomy 30–32 weeks. And it became apparent that the frequency of hysterectomy, cerebral palsy and neonatal death were higher in the cases of uterine rupture during labor than before delivery. Among the cases of scarred uterine rupture, neonatal prognosis was poorer in cases of pregnancy after myomectomy or adenomyomectomy in comparison with postcesarean section cases.

Conclusion

This survey revealed the current incidence of uterine rupture in Japan.
Effect of oral supplementation of probiotic strains of Lactobacillus rhamnosus and Enterococcus faecium on the composition of the faecal microbiota of foals
Authors: Urubschurov Vladimir , Stroebel Christina , Günther Elena , Romanowski Kristin , Büsing Kirsten , Zeyner Annette
Published: March 2019

Effects of probiotics on the intestinal microbiota of foals are yet insufficiently studied. The aim of this study was to investigate whether supplementation of Lactobacillus rhamnosus (DSM 7133) and Enterococcus faecium (DSM 7134) influences the bacterial composition of the faecal microbiota of foals. A total of 34 newborn foals were randomly assigned to the placebo group (PG, n = 16) and the treatment group (TG, n = 18). From day 1 to day 14 of life, foals orally received 3 ml of either a probiotic preparation (1.05 × 109 CFU E. faecium and 4.50 × 108 CFU L. rhamnosus) or placebo (carrier) once a day. Faeces were collected directly from the rectum immediately after birth (meconium) and at day 14 and day 56 of life. Samples of 12 foals per group were selected for microbiological analysis. DNA was extracted and used for polymerase chain reaction–denaturing gradient gel electrophoresis (PCR‐DGGE) and quantitative PCR. No DNA or amplicons were obtained from meconium. There were no differences in richness of bands and Shannon index of diversity regarding the Clostridium cluster XIVa between groups. Cluster analysis and principal coordinate analysis of DGGE data showed a clear effect of age. Band‐based similarity of bacterial clusters (Dice coefficient) decreased from day 14 to day 56 of life (p < 0.001) in PG foals only resulting in lower similarity in PG versus TG foals when 2 month old (p < 0.01). Five of thirty re‐amplified bands were identified on species level. Others were assigned either to family (mainly Lachnospiraceae) or genus level (Akkermansia). The bands related to Akkermansia muciniphila or Akkermansia spp. appeared almost in all DGGE profiles. Two‐week supplementation of the probiotic preparation to foals had no significant impact on the composition of the faecal microbiota but it appears to have prevented the reduction of bacterial similarity between 2 and 8 weeks of age observed in not treated foals.
No differences in microbiome changes between anti‐adhesive and antibacterial ingredients in toothpastes during periodontal therapy
Authors: Hagenfeld Daniel , Prior Karola , Harks Inga , Jockel‐Schneider Yvonne , May Theodor W. , Harmsen Dag , Schlagenhauf Ulrich , Ehmke Benjamin
Published: March 2019

Aim

This subgroup analysis of a 12‐week randomized, double‐blind, and two‐center trial aimed to evaluate whether two different toothpaste formulations can differentially modulate the dental microbiome.

Material and Methods

Forty one mild to moderate periodontitis patients used as an adjunct to periodontal treatment either a toothpaste with anti‐adhesive zinc‐substituted carbonated hydroxyapatite (HA) or with antimicrobial and anti‐adhesive amine fluoride/stannous fluoride (AmF/SnF2) during a 12‐week period. Plaque samples from buccal/lingual, interproximal, and subgingival sites were taken at baseline, 4 weeks after oral hygiene phase, and 8 weeks after periodontal therapy. Samples were analyzed with paired‐end Illumina Miseq 16SrDNAsequencing. The differences and changes on community level (alpha and beta diversity) and on the level of single agglomerated ribosomal sequence variants (aRSV) were calculated with analysis of covariance (ANCOVA) and likelihood ratio test (LRT).

Results

Interproximal and subgingival sites harbored predominatelyFusobacteriumandPrevotellaspecies associated with periodontitis, whereas buccal/lingual sites harbored mainlyStreptococcusandVeillonellaspecies associated with periodontal health. Alpha and beta diversity did not change noticeably differently between both toothpaste groups (P > 0.05,ANCOVA). Furthermore, none of theaRSVs showed a noticeably different change between the tested toothpastes during periodontal therapy (Padj .> 0.05,LRT).

Conclusion

The use of a toothpaste containing anti‐adhesiveHAdid not induce statistically noticeably different changes on microbial composition compared to an antimicrobial and anti‐adhesive AmF/SnF2formulation.