bluuebunny/crossref_metadata_2025 huggingface dataset:
Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K‐AKT‐NFATc1 pathway
Authors: Cui Jin , Li Xiaoqun , Wang Sicheng , Su Yiming , Chen Xiao , Cao Liehu , Zhi Xin , Qiu Zili , Wang Yao , Jiang Hao , Huang Biaotong , Ji Fang , Su Jiacan
Published: April 2020

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro‐architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti‐cancer, anti‐inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL‐induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K‐AKT‐NFATc1 pathway is one of the most important downstream pathways of RANKL‐induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K‐AKT‐NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM‐p53‐induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy‐induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti‐cancer drug triptolide was demonstrated to be anti‐osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.
Can mandatory certification promote greenwashing? A signaling approach
Authors: Garrido Dolores , Espínola‐Arredondo Ana , Munoz‐Garcia Felix
Published: April 2020

This paper examines how positive or negative perceptions about innovation affect firms' strategic behavior when certifying their products. In particular, we consider two types of firm (innovative and noninnovative) which choose between three signals: (a) certified claim, (b) uncertified claim, and (c) no claim. The consumer, either exhibiting positive or negative perceptions, is uninformed about the firm's type and only observes the firm's claim. We find that a separating equilibrium arises in which information about the innovation is revealed to consumers. We also identify a pooling equilibrium in which both types of firm choose the same claim, concealing information from consumers. We show that regulation requiring mandatory certification can hinder information transmission. Our results also indicate that changes in product perceptions do not necessarily facilitate information transmission.
Precision dosing-based optimisation of paroxetine during pregnancy for poor and ultrarapid CYP2D6 metabolisers: a virtual clinical trial pharmacokinetics study
Authors: Almurjan Aminah , Macfarlane Hannah , Badhan Raj K S
Published: April 2020

Objective

Paroxetine has been demonstrated to undergo gestation-related reductions in plasma concentrations, to an extent which is dictated by the polymorphic state of CYP 2D6. However, knowledge of appropriate dose titrations is lacking.

Methods

A pharmacokinetic modelling approach was applied to examine gestational changes in trough plasma concentrations for CYP 2D6 phenotypes, followed by necessary dose adjustment strategies to maintain paroxetine levels within a therapeutic range of 20–60 ng/ml.

Key findings

A decrease in trough plasma concentrations was simulated throughout gestation for all phenotypes. A significant number of ultrarapid (UM) phenotype subjects possessed trough levels below 20 ng/ml (73–76%) compared to extensive metabolisers (EM) (51–53%).

Conclusions

For all phenotypes studied, there was a requirement for daily doses in excess of the standard 20 mg dose throughout gestation. For EM, a dose of 30 mg daily in trimester 1 followed by 40 mg daily in trimesters 2 and 3 is suggested to be optimal. For poor metabolisers (PM), a 20 mg daily dose in trimester 1 followed by 30 mg daily in trimesters 2 and 3 is suggested to be optimal. For UM, a 40 mg daily dose throughout gestation is suggested to be optimal.
Pharmacokinetic, bioavailability and tissue distribution study of astilbin in rats
Authors: Shi Meiyun , Xu Mengyao , Yin Lei
Published: April 2020

Objective

The purpose of this study is to reveal the pharmacokinetic profiles of astilbin with various doses in rats and investigate the oral absolute bioavailability and tissue distribution of astilbin after oral administration.

Methods

Wistar rats were orally administered astilbin 12, 24 mg/kg and intravenous administered astilbin 6 mg/kg randomly. The concentration of astilbin in rat plasma and various tissue samples was determined by LC-MS/MS method. Noncompartmental pharmacokinetic parameters including AUC and t1/2 were calculated from plasma concentration–time data of astilbin with the DAS 3.0.

Key findings

After oral administration of astilbin 12 and 24 mg/kg to rats, the oral absolute bioavailability of astilbin were 1.16 ± 0.695% and 1.27 ± 0.379%; the plasma elimination half-lives (t1/2) were 101 ± 35.8 and 109 ± 25.3 min, respectively. Astilbin had a rapid absorption and a wide distribution throughout the whole body except liver and fat following oral administration. Astilbin could penetrate the blood–brain barrier of rat.

Conclusions

The oral absolute bioavailability of astilbin is poor because of the low permeability and solubility. Both oral absorption and clearance of astilbin in rats are rapid after oral administration.
Revival of Ancient Marine Dinoflagellates Using Molecular Biostimulation
Authors: Delebecq Gaspard , Schmidt Sabine , Ehrhold Axel , Latimier Marie , Siano Raffaele
Published: April 2020

The biological processes involved in the preservation, viability, and revival of long‐term dormant dinoflagellate cysts buried in sediments remain unknown. Based on studies of plant seed physiology, we tested whether the revival of ancient cysts preserved in century‐old sediments from the Bay of Brest (France) could be stimulated by melatonin and gibberellic acid, two molecules commonly used in seed priming. Dinoflagellates were revived from sediments dated to approximately 150 years ago (156 ± 27, 32 cm depth), extending the known record age of cyst viability previously established as around one century. A culture suspension of sediments mixed with melatonin and gibberellic acid solutions as biostimulants exhibited germination of 11 dinoflagellate taxa that could not be revived under controlled culture conditions. The biostimulants revived some dinoflagellates from century‐old sediments, including the potentially toxic species Alexandrium minutum. The biostimulants showed positive effects on germination on even more ancient cysts, showing dose‐dependent effects on the germination of Scrippsiella acuminata. Concentrations of 1, 10, and 100 µM melatonin and gibberellic acid promoted germination. In contrast, 1,000 µM solutions, particularly for melatonin, drastically decreased germination, suggesting a potential noxious effect of high doses of these molecules on dinoflagellate revival. Our findings suggest that melatonin and gibberellic acid are involved in the stimulation of germination of dinoflagellate cysts. These biostimulants can be used to germinate long‐term stored dinoflagellate cysts, which may promote studies of ancient strains in the resurrection ecology research field.
On the three‐step non‐Gaussian quasi‐maximum likelihood estimation of heavy‐tailed double autoregressive models
Authors: Gong Huan , Li Dong
Published: April 2020

This note considers a three‐step non‐Gaussian quasi‐maximum likelihood estimation (TS‐NGQMLE) of the double autoregressive model with its asymptotics, which improves efficiency of the GQMLE and circumvents inconsistency of the NGQMLE when the innovation is heavy‐tailed. Under mild conditions, the estimator not only can achieve consistency and asymptotic normality regardless of density misspecification of the innovation, but also outperforms the existing estimators, such as the GQMLE and the (weighted) least absolute deviation estimator, when the innovation is indeed heavy‐tailed.
Combined Application of Dexamethasone and Tranexamic Acid to Reduce the Postoperative Inflammatory Response and Improve Functional Outcomes in Total Hip Arthroplasty
Authors: An Yu‐zhang , Xu Ming‐deng , An Yu‐cheng , Liu Huan , Zheng Ming , Jiang Dian‐ming
Published: April 2020

Objective

To evaluate the efficacy and safety of combined use of tranexamic acid (TXA) and dexamethasone (DEX) for anti‐inflammatory and clinical outcomes after total hip arthroplasty (THA).

Methods

A total of 100 patients were included in this randomized, controlled study. Patients in the TXA + DEX group were administered TXA at a dose of 15 mg/kg, which was repeated 3 h after THA, and received 20 mg DEX. In contrast, patients in the TXA group were administered TXA at a dose of 15 mg/kg, which was repeated at 3 h postoperatively. C‐reactive protein (CRP), interleukin‐6 (IL‐6) and pain levels, incidence of postoperative nausea and vomiting (PONV), total blood loss and transfusion rates, postoperative fatigue, range of motion (ROM), length of hospital stay (LOS), analgesic rescue and antiemetic rescue consumption, and complications were compared in both groups.

Results

The CRP and IL‐6 levels were lower in the TXA + DEX group than in the TXA group (all P < 0.001) at 24 h, 48 h, and 72 h postoperatively. Patients in the TXA + DEX group had lower pain scores at rest and walking at 24 h postoperatively (all P < 0.001). In the TXA + DEX group, the incidence of PONV was lower (P = 0.005), postoperative fatigue (P < 0.001) was reduced, and analgesia and antiemetic rescue consumption were also reduced. The total blood loss, transfusion rate, LOS and hip ROM were similar in the two groups. There was no thrombosis, infection, or gastrointestinal bleeding in either group.

Conclusion

Compared to TXA alone, the combination of TXA + DEX can reduce postoperative inflammatory response, relieve pain, and reduce PONV and fatigue, without increasing the risk of complications. Therefore, the present study suggested that the combination of TXA + DEX is an effective and safe accelerated rehabilitation strategy for patients receiving primary unilateral THA.
The changing resistance patterns of bacterial uropathogens in children
Authors: Kurt‐Şükür Eda Didem , Özçakar Zeynep Birsin , Doğan Özlem , Öztürk Musa , Karaman Merve , Çakar Nilgün , Güriz Haluk , Yalçınkaya Fatoş
Published: April 2020

Background

Increased antimicrobial resistance is a problem in managing urinary tract infections (UTI). With this study we assessed the resistance patterns of urinary isolates in children with UTI between January 2017 and January 2018.

Methods

A retrospective cohort study was conducted. Among 5,443 isolates, a total of 776 UTI episodes in 698 patients were included. Patients' gender, age, voiding dysfunction, UTI history, prophylaxis status, and presence of vesicoureteral reflux were noted. Patients were divided into three age groups: group 1 for ages ≤12 months; group 2 for ages 13–60 months; and group 3 for ages >60 months. The susceptibilities of etiologic agents to different antimicrobials were explored.

Results

Median age was 54 months (range 1 month–21 years); male to female ratio was 1:5. The most common causative agent was Escherichia coli (83% of the cases), followed by Klebsiella pneumoniae (7.5%). Resistance to ampicillin (62.6%) and co‐trimoxazole (39.8%) were remarkable in all isolates. Overall extended‐spectrum beta‐lactamase (ESBL) positivity was 23.5%. The highest resistance rates, higher ESBL positivity (28.6%), and K. pneumoniae frequency (13.5%) were observed in group 1. Ceftriaxone resistance was significantly low (0.5%) in the ESBL (−) group, which constituted the majority of the isolates. Higher resistance rates were observed among the patients on prophylaxis compared to those off prophylaxis (P < 0.001).

Conclusion

Ceftriaxone can still be used for empirical treatment; however, initial urine culture results are crucial due to high ESBL positivity. Special consideration must be taken for patients under 1 year of age. Periodical surveillance studies are needed to explore the changing resistance patterns of uropathogens and modify treatment plans.
Genome‐wide association study for spot blotch resistance in Afghan wheat germplasm
Authors: Bainsla Naresh K. , Phuke Rahul M. , He Xinyao , Gupta Vikas , Bishnoi Santosh K. , Sharma Rajiv K. , Ataei Najibeh , Dreisigacker Susanne , Juliana Philomin , Singh Pawan K.
Published: April 2020

Spot blotch (SB), caused by Bipolaris sorokiniana, is a devastating disease of wheat globally, especially in South Asia and South America. Understanding the genetics of resistance to SB is important for developing breeding strategies to improve resistance. A panel of 301 genotypes from Afghanistan was phenotyped over two crop seasons using a mixture of virulent B. sorokiniana isolates and genotyped using DArTSeq to obtain genome‐wide markers. Fifty genotypes (16.6%) showed disease scores less than the resistant control. Principal component analysis using the genotypic data clustered the genotypes into five different groups. Among models used for genome‐wide association mapping, the multilocus mixed model, and fixed and random model circulating probability unification algorithms were most effective in identifying significant marker‐trait associations (MTA). Twenty‐five MTAs at p ≤ .001 were identified on chromosomes 1A, 1B, 1D, 2B, 2D, 3A, 3B, 4A, 5A, 5B, 6A, 7A, and 7D, indicating the quantitative nature of resistance to SB. Phenotypic variation explained by these markers ranged from 2.0% to 17.7%, and genomic regions on the chromosomes 1D, 2D, 3A, 3B, 4A, 5A, and 5B coincided with loci identified in previous studies. Three single nucleotide polymorphism (SNP) markers on chromosomes 1B (SNP 1113207) and 5A (SNPs 5411867 and 998276) were significant in both crop seasons as well as in the combined analysis across seasons. Marker 5411867 is close to Vrn‐A1, shown to be associated with SB in previous studies. Furthermore, among known SB resistance genes, Sb2 on chromosome 5B was predicted to be significant in this panel.
Paediatric acute lymphoblastic leukaemia and caesarean section: A report from the United Kingdom Childhood Cancer Study (UKCCS)
Authors: Bonaventure Audrey , Simpson Jill , Ansell Pat , Roman Eve
Published: April 2020

Background

Reports have suggested that children born by caesarean initiated before labour onset may be at increased risk of developing acute lymphoblastic leukaemia (ALL). However, with most data being derived from case‐control study interviews, information on the underpinning reasons for caesarean section is sparse, and evidence is conflicting.

Objectives

Use clinical records compiled at the time of delivery to investigate the association between childhood ALL and caesarean delivery; examining timing in relation to labour onset, and reasons for the procedure.

Methods

Data are from the UK Childhood Cancer Study, a population‐based case‐control study conducted in the 1990s, when caesarean section rates were relatively low, in England, Scotland, and Wales. Children with ALL were individually matched to two controls on sex, date of birth, and region of residence. Information on mode of delivery and complications was abstracted from obstetric records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models adjusted for matching variables and relevant covariates.

Results

Around 75% of the 1034 cases and 1914 controls were born through unassisted vaginal delivery. Caesarean delivery was as frequent in cases and controls (OR 1.07, 95% CI 0.84, 1.36). No association was observed between ALL and caesarean delivery either during or before labour, with adjusted ORs of 1.08 (95% CI 0.78, 1.48) and 1.09 (95% CI 0.78, 1.53), respectively. For B‐cell ALL, the ORs were 1.14 (95% CI 0.81, 1.59) for caesarean during labour and 1.21 (95% CI 0.85, 1.72) for prelabour. The underpinning reasons for caesarean delivery differed between cases and controls; with preeclampsia, although very rare, being more common amongst cases born by caesarean (OR 8.91, 95% CI 1.48, 53.42).

Conclusions

Our obstetric record‐based study found no significant evidence that caesarean delivery increased the risk of childhood ALL, either overall or when carried out before labour.
Modeling Poliovirus Transmission in Borno and Yobe, Northeast Nigeria
Authors: Kalkowska Dominika A. , Franka Richard , Higgins Jeff , Kovacs Stephanie D. , Forbi Joseph C. , Wassilak Steven G. F. , Pallansch Mark A. , Thompson Kimberly M.
Published: April 2020

Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine‐derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security‐compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation‐based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.
Identifiability and estimation of recursive max‐linear models
Authors: Gissibl Nadine , Klüppelberg Claudia , Lauritzen Steffen
Published: April 2020

We address the identifiability and estimation of recursive max‐linear structural equation models represented by an edge‐weighted directed acyclic graph (DAG). Such models are generally unidentifiable and we identify the whole class of DAG s and edge weights corresponding to a given observational distribution. For estimation, standard likelihood theory cannot be applied because the corresponding families of distributions are not dominated. Given the underlying DAG, we present an estimator for the class of edge weights and show that it can be considered a generalized maximum likelihood estimator. In addition, we develop a simple method for identifying the structure of the DAG. With probability tending to one at an exponential rate with the number of observations, this method correctly identifies the class of DAGs and, similarly, exactly identifies the possible edge weights.
Multivariate extremes over a random number of observations
Authors: Hashorva Enkelejd , Padoan Simone A. , Rizzelli Stefano
Published: April 2020

The classical multivariate extreme‐value theory concerns the modeling of extremes in a multivariate random sample, suggesting the use of max‐stable distributions. In this work, the classical theory is extended to the case where aggregated data, such as maxima of a random number of observations, are considered. We derive a limit theorem concerning the attractors for the distributions of the aggregated data, which boil down to a new family of max‐stable distributions. We also connect the extremal dependence structure of classical max‐stable distributions and that of our new family of max‐stable distributions. Using an inversion method, we derive a semiparametric composite‐estimator for the extremal dependence of the unobservable data, starting from a preliminary estimator of the extremal dependence of the aggregated data. Furthermore, we develop the large‐sample theory of the composite‐estimator and illustrate its finite‐sample performance via a simulation study.
Do the Affluent Override Average Americans? Measuring Policy Disagreement and Unequal Influence
Authors: Bowman Jarron
Published: April 2020

Objective

In this article, I seek to adjudicate between contradictory findings in studies of unequal responsiveness that focus on policy issues over which affluent and average Americans disagree.

Methods

I assess the impact of 22 definitions of policy disagreement and two methods of measuring policy influence—based on win rates and policy change rates—on analyses of unequal responsiveness.

Results

Win rates are an unreliable measure of influence and comparing policy change rates across cases of agreement and disagreement minimizes bias and allows for a more direct measure of relative independent policy influence. When income groups disagree over proposed policy changes, the preferences of the affluent—but not those of the middle—significantly impact the likelihood that the policies are implemented.

Conclusion

My results support previous findings that the affluent have substantial influence over policy making while average Americans have little to no influence.
Impact of COVID‐19 on blood centres in Zhejiang province China
Authors: Wang Yongjun , Han Wenjuan , Pan Lingling , Wang Cuier , Liu Yan , Hu Wei , Zhou Huapin , Zheng Xiaofan
Published: April 2020

Background and Objectives

A worldwide pandemic of coronavirus disease 2019 (COVID‐19) has affected millions of people. A ‘closed‐off management’ protocol has been launched nationwide in China to cope with this major public health emergency. However, these procedures may cause a crisis for blood donation and blood supply. In this study, we assessed the impact of the COVID‐19 pandemic on blood donation and supply in Zhejiang province, which could provide reference and insight for developing countermeasures in other countries.

Materials and Methods

Blood donor and supply information from 38 blood centres during the Spring Festival of 2019 and 2020 were reviewed. A self‐administered questionnaire was carried out.

Results

Due to the COVID‐19 pandemic, the number of whole blood donors dropped by 67%. The success rate of recruitment for donations dropped by 60%. Most respondents (81·2%) were worried about the ‘possibility of acquiring COVID‐19 during blood donation’. The total amount of RBCs supply dropped by 65%. In the first week of the outbreak, the weekly amount of issued RBC units (10171·5 u) was almost six times higher than the collected units (1347·5 u). The mean haemoglobin value for RBCs transfusion was about 6·3 g/dl. About 4% of RBCs and 2·8% of frozen plasma were used in COVID‐19 patients.

Conclusion

The secondary consequences of the COVID‐19 pandemic are blood shortages caused by the unavailability of blood donors, and this is likely to be replicated in many countries with high burdens of COVID‐19. Practical actions to broaden sources and reduce use for the global crisis must be taken proactively.
Thermal Stability Analysis of Nonlocal Temperature-Dependent Functionally Graded Tapered Timoshenko Nanobeam
Authors: Lal Roshan , Dangi Chinika
Published: April 2020

Analysis on buckling behavior of functionally graded (FG) Timoshenko nanobeam with cross-sectional variation induced by nonlinear temperature (NLT) field has been presented on the basis of first-order shear deformation theory in conjunction with Eringen's nonlocal elasticity theory. The cross-sectional nonuniformity of the beam is assumed to arise due to linear variation in thickness along the length. The material composition of the beam varies in thickness direction according to a power-law function and depends upon temperature. For the first time in case of nanobeam, the dependency of temperature has been incorporated in the analysis by using an iterative procedure for computing the material properties at current temperature instead of ambient temperature which gives a more accurate approximation for the temperature-dependent material properties. The governing equations of buckling for such a beam model have been developed using minimum energy principle and solved numerically using generalized differential quadrature method (GDQM) for three different edge conditions. A significant contribution of nonuniformity in the cross section on thermal buckling behavior of Timoshenko nanobeam has been noticed.
Leg Joint Stiffness Affects Dynamics of Backward Falling From Standing Height: A Simulation Work
Authors: Qiao Mu , Yang Feng
Published: April 2020

Falling backward can lead to injuries including hip fracture, back injury, and traumatic brain impact among older adults. A loss of consciousness is associated with falling backward and accounts for about 13% of all falls among older adults. Little is known about the dynamics of backward falls, such as the falling duration, the impact severity, and how the fall dynamics are affected by the biomechanical properties of the lower limb joints, particularly the rotational stiffness. The purpose of this study was to investigate the influence of the stiffness of individual leg joints on the dynamics of backward falls after losing consciousness in terms of the falling duration and impact velocities. Based on a 15-segment human model, we simulated the process of falling backward by sweeping the parameter space of ankle, knee, and hip's stiffnesses varying from 0 to 8.73 N·m·deg−1 (or 500 N·m·rad−1). The results revealed that the falling duration and impact speeds of the head and hip ranged from 0.27 to 0.63 s, 2.65 to 7.88 m·s−1, and 0.35 to 3.36 m·s−1, respectively, when the stiffness of the leg joints changed within their limits. Overall, the influence of the joint stiffness on the falling dynamics (falling duration and impact speed) is comparable between hip and knee joints, whereas ankle stiffness showed little influence on the backward falling dynamics. Our findings could provide references for designing protective devices to prevent impact-induced injuries after a backward fall.
CDK13 cooperates with CDK12 to control global RNA polymerase II processivity
Authors: Fan Zheng , Devlin Jennifer R. , Hogg Simon J. , Doyle Maria A. , Harrison Paul F. , Todorovski Izabela , Cluse Leonie A. , Knight Deborah A. , Sandow Jarrod J. , Gregory Gareth , Fox Andrew , Beilharz Traude H. , Kwiatkowski Nicholas , Scott Nichollas E. , Vidakovic Ana Tufegdzic , Kelly Gavin P. , Svejstrup Jesper Q. , Geyer Matthias , Gray Nathanael S. , Vervoort Stephin J. , Johnstone Ricky W.
Published: April 2020

CDK12 and CDK13 regulate POLII elongation rate and processivity and influence the selection of transcription termination sites.
Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition
Authors: Akoumianakis Ioannis , Badi Ileana , Douglas Gillian , Chuaiphichai Surawee , Herdman Laura , Akawi Nadia , Margaritis Marios , Antonopoulos Alexios S. , Oikonomou Evangelos K. , Psarros Costas , Galiatsatos Nikolaos , Tousoulis Dimitris , Kardos Attila , Sayeed Rana , Krasopoulos George , Petrou Mario , Schwahn Uwe , Wohlfart Paulus , Tennagels Norbert , Channon Keith M. , Antoniades Charalambos
Published: April 2020

Vascular oxidative stress in human atherosclerosis is reversed by restoring vascular insulin sensitivity using a dipeptidyl peptidase 4 inhibitor.
An ounce of public health for COVID-19?
Authors: Nadkarni Girish N.
Published: April 2020

Multifaceted nonpharmaceutical interventions supported by data restricted spread of COVID-19 in China.
OpiA, a Type Six Secretion System Substrate, Localizes to the Cell Pole and Plays a Role in Bacterial Growth and Viability inFrancisella tularensisLVS
Authors: Cantlay Stuart , Haggerty Kristen , Horzempa Joseph
Published: April 2020

F. tularensisis a pathogenic intracellular pathogen that is of importance for public health and strategic defense. This study characterizes theopiAgene ofF. tularensisLVS, an attenuated strain that has been used as a live vaccine but that also shares significant genetic similarity to relatedFrancisellastrains that cause human disease. The data presented here provide the first evidence of a T6SS effector protein that affects the physiology ofF. tularensis, namely, the growth, cell size, viability, and aminoglycoside resistance ofF. tularensisLVS. This study also adds insight into our understanding of OpiA as a determinant of virulence. Finally, the fluorescence fusion constructs presented here will be useful tools for dissecting the role of OpiA in infection.
Resolution of Streptococcus suis Serotypes 1/2 versus 2 and 1 versus 14 by PCR-Restriction Fragment Length Polymorphism Method
Authors: Matiasovic Jan , Zouharova Monika , Nedbalcova Katerina , Kralova Natalie , Matiaskova Katarina , Simek Bronislav , Kucharovicova Ivana , Gottschalk Marcelo
Published: April 2020

Streptococcus suis
is an important pathogen of pigs but is also transmissible to humans, with potentially fatal consequences. Among 29 serotypes currently recognized, some are clinically and epidemiologically more important than others. This is particularly true for serotypes 2 and 14, which have a large impact on pig production and also on human health. Conventional PCR-based serotyping cannot distinguish between serotype 1/2 and serotype 2 or between serotype 1 and serotype 14.
Draft Genome Sequence of
Clostridium
sp. Strain FP1, with Similarity to
Clostridium tagluense
, Isolated from Spoiled Lamb
Authors: Palevich Nikola , Palevich Faith P. , Maclean Paul H. , Jauregui Ruy , Altermann Eric , Mills John , Brightwell Gale
Published: April 2020

Clostridium
sp. strain FP1 was isolated from vacuum-packaged refrigerated spoiled lamb, and this article describes its 5.4-Mb draft genome sequence. The FP1 genome was sequenced to facilitate source tracking and attribution studies, adding to our understanding of the role of
Clostridium
species in premature spoilage of red meats.
Geological alteration of organic macromolecules by irradiation: Implication for organic matter occurrence on Mars
Authors: Yang Shengyu , Schulz Hans-Martin , Horsfield Brian , Schovsbo Niels H. , Grice Kliti , Zhang Jinchuan
Published: April 2020

The harsh radiation environment on Mars is widely believed to destroy organic matter, but elucidating the systematic degradation pathway and its controlling factors has proved elusive. Here we show the alteration of macromolecular organic matter in the ∼500-m.y.-old uranium-rich Alum Shale Formation (northwestern Europe), which is suggested as a geological analogue on Earth of the Martian surface samples, in response to ⟨-particle irradiation. The composition and quantity of pyrolysates as well as the extractability of immature Alum Shale are governed by uranium content, and this has been confirmed independently using uranium-rich shales of younger geological age. During the course of irradiation, macromolecules undergo cross-linking, demethylation, and aromatization processes, which are active at different stages in the alteration of the organic matter. A comparison of the Martian surface samples with Kolm (carbonaceous nodules with very high uranium content intercalated in the Alum Shale) samples in terms of irradiation dosage and organic geochemical characteristics reveals that they have received similar levels of irradiation. A model of the radiation-induced alteration of organic matter has been developed, which opens a window for understanding the possible pristine nature and composition of the irradiated organic matter on Mars and offers arguments to qualitatively predict potential organic matter in the Martian paleo-lacustrine subsurface.
Radioisotopic and biostratigraphic constraints on the classical Middle–Upper Permian succession and tetrapod fauna of the Moscow syneclise, Russia
Authors: Davydov V.I. , Arefiev M.P. , Golubev V.K. , Karasev E.V. , Naumcheva M.A. , Schmitz M.D. , Silantiev V.V. , Zharinova V.V.
Published: April 2020

The East European Platform and the PreUrals are the regions where the Permian System was first established, but the provincialism of fossils and lack of radioisotopic age control have prevented the use there of the regional Permian subdivisions used outside of the region. We report the first U-Pb zircon chemical abrasion–isotope dilution–thermal ionization mass spectrometry (CA-ID-TIMS) age of 253.95 ± 0.06 Ma for a volcanic tuff from the terrestrial upper part of the lower Vyatkian Regional Stage in the Moscow syneclise (Russia). This age greatly improves the correlation of the East European Platform and the PreUrals with the international geologic time scale, and contributes to our understanding of sedimentation within the Permian-Triassic transition in the studied region. The new radioisotopic age integrated within the regional chronostratigraphic framework reveals the synchrony in extinction of faunas of the Dinocephalian superassemblage in the studied region with that in South Africa.
Diverse rock types detected in the lunar South Pole–Aitken Basin by the Chang’E-4 lunar mission
Authors: Huang (黄俊) Jun , Xiao (肖智勇) Zhiyong , Xiao (肖龙) Long , Horgan Briony , Hu (胡晓依) Xiaoyi , Lucey Paul , Xiao (肖潇) Xiao , Zhao (赵思源) Siyuan , Qian (钱煜奇) Yuqi , Zhang (张昊) Hao , Li (李春来) Chunlai , Xu (徐睿) Rui , He (何志平) Zhiping , Yang (杨建峰) Jianfeng , Xue (薛彬) Bin , He (何琦) Qi , Zhong (钟杰) Jie , Lin (林宏宇) Hongyu , Huang (黄长宁) Changning , Xie (谢剑锋) Jianfeng
Published: April 2020

The South Pole–Aitken (SPA) basin, located between the South Pole and Aitken crater on the far side of the Moon, is the largest confirmed lunar impact structure. The pre-Nectarian SPA basin is a 2400 × 2050 km elliptical structure centered at 53°S, 191°E, which should have exposed lower crust and upper mantle due to the enormous excavation depth. Olivine, the dominant mineral in Earth’s mantle, has only been identified in small and localized exposures in the margins of the SPA basin, and the dominant mafic component is, instead, pyroxene. These mineralogical characteristics could be explained by the recent hypothesis that the lunar upper mantle is dominated by low-calcium pyroxene, not olivine. Here, we present observations from imaging and spectral data from China’s Chang’E-4 (CE-4) lunar mission in the first 4 synodic days, especially the first in situ visible/near-infrared spectrometer observations of an exposed boulder. We identified a variety of rock types, but not the recently reported olivine-rich materials in the landing region. The results are consistent with orbital observations. The obtained mineralogical information provides a better understanding of the nature and origin of SPA materials.
Using speleothems to constrain late Cenozoic uplift rates in karst terranes
Authors: Engel John , Woodhead Jon , Hellstrom John , White Susan , White Nicholas , Green Helen
Published: April 2020

The utility of speleothems as environmental and geological archives has greatly expanded with recent advances in geochronology. Here we reevaluate their ability to constrain late Cenozoic uplift in karst terranes. Using combined U-Th and U-Pb speleothem chronologies for the Buchan karst along the passive margin of southeastern Australia, we calculate a maximum uplift rate of 76 ± 7 m m.y.−1 maintained over the past 3.5 m.y. The timing and extent of this process is consistent with independent constraints on Neogene uplift in Australia, possibly in response to increased plate-boundary strain with New Zealand. Speleothem chronologies provide highly precise age control on individual events and the potential for near-continuous records across long periods of geological time, complementing and expanding upon existing uplift proxies.
Pitfalls of using denosumab preoperatively to treat refractory severe hypercalcaemia
Authors: Li Yulong , Fan Chris Y , Manni Andrea , Simonds William F
Published: April 2020

A 40-year-old man, with a history of metastatic parathyroid carcinoma, status post primary tumour resection and lung metastasectomy, was hospitalised for persistent severe hypercalcaemia and elevated parathyroid hormone levels despite conventional management and escalating doses of cinacalcet. A single dose (120 mg) of denosumab was given and his calcium level plummeted from 14.8 mg/dL to 5.5 mg/dL. After second lung metastasectomy, he developed prolonged hypocalcaemia that required calcium and vitamin D supplements for more than 3 years. In patients with severe hypercalcaemia refractory to conventional therapies, denosumab has been used off-label with some success. A known side effect of denosumab is hypocalcaemia, which is often short-lived. The risk of prolonged hypocalcaemia should be fully evaluated before using denosumab preoperatively, especially in patients with renal insufficiency, prolonged hyperparathyroidism or anticipated tumour debulking surgery.
Aggressive angiomyxoma presenting as an ischiorectal fossa tumour
Authors: Cabanilla-Manuntag Ma Corazon Concepcion , Lopez Marc Paul Jose , Tampo Mayou Martin , Gaston Czar Louie
Published: April 2020

This is a case of a young healthy woman who presented with left groin pain. On work-up, she was found to have a large, well-defined mass in the ischiorectal fossa with a percutaneous biopsy of only a benign mesenchymal mass. A multidisciplinary team of surgeons (ie, colorectal, orthopaedic, vascular and urological surgery) collaborated in planning and performing the extirpation of the tumour. Final histopathology identified the tumour to be an aggressive angiomyxoma, a benign tumour with a high predilection for local recurrence. The patient had an uneventful postoperative course, with maintenance of good functional status.
Frontal lobe meningioma presenting with schizophrenia-like symptoms: an organic cause of psychotic disorder
Authors: Suradom Chawisa , Suttajit Sirijit , Soontornpun Atiwat , Pinyopornpanish Manee
Published: April 2020

A 51-year-old woman had been diagnosed and treated for schizophrenia for 10 years. Two weeks prior to admission, she developed headache and diplopia. Then, she was found unconscious and was sent to the hospital. A tumour in the left frontal lobe of the brain, causing brain herniation, was diagnosed and surgical excision of tumour was performed immediately. The psychotic symptoms of the patient were completely resolved after surgery. The histological diagnosis was meningioma. This case demonstrates an uncommon presentation of meningioma, the most common primary brain tumour. Patients presenting with psychotic symptoms may be misdiagnosed with schizophrenia, when a tumour is present, allowing the tumour to grow and causing associated complications. Early diagnosis and treatment could prevent mortality and morbidity. The treating physician should be aware of organic possibilities and carefully search for atypical presentations of psychiatric disorders in their patients.
Transient global amnesia following transoesophageal echocardiography
Authors: Cassar Mark Philip , Balkhausen Katrin
Published: April 2020

Transient global amnesia (TGA) is characterised by the sudden onset of isolated anterograde amnesia, which resolves within 24 hours. Here, we discuss the case of a 63-year-old woman who underwent a transoesophageal echocardiogram (TOE) as part of her workup for pulmonary hypertension. She was well on the morning of the procedure, and following consent, underwent transoesophageal echocardiography without sedation. The procedure was uncomplicated with normal observations throughout, confirming a suspected secundum atrial septal defect. Immediately following oesophageal extubation, it was noted that the patient was disoriented. The physical neurological examination was unremarkable. Urgent MRI of the brain showed normal anatomy; a diagnosis of TGA was made. Within 10 hours of onset, the patient was back to her baseline. Isolated anterograde amnesia following transoesophageal echocardiography should raise the clinical suspicion of TGA. Prompt clinical examination and support from other specialties are paramount in making the right diagnosis.
Role of the pre-hospital treatment team on the UK military exercise SAIF SAREEA 3
Authors: Harper Peter Nicholas , Taylor N , Royal P , Smith MB
Published: April 2020

The prehospital treatment team (PHTT) involves a small team working under the clinical supervision of a clinical lead. The clinical lead can be a general duties medical officer (Post Foundation Years Doctor), military nurse practitioner or more senior clinician. The team is mounted in vehicles appropriate to the environment they expect to operate in. A PHTT is closely located to the front line reducing transportation timelines from the point of wounding to more definitive care. The PHTT can provide medical support on the move or when time is available; a more permanent fully erected treatment facility can be established. Either configuration can provide both trauma and primary care. The size of the team allows for multiple trauma subteams enabling care to casualties that arrive simultaneously. The PHTT can move independently which could leave the team vulnerable as there is no integral force protection within the current structure. In such a small team, the right balance of medical and soldiering skills among team members is essential to success. Exercise SAIF SAREEA 3 represented a large-scale battlegroup exercise to the Middle East in the austere desert of Oman. This provided an ideal environment for employing the PHTT concept is a large deployed force undertaking dynamic activity.
Alcohol screening and brief intervention among military service members and veterans: rural–urban disparities
Authors: McDaniel Justin T , Albright D L , Laha-Walsh K , Henson H , McIntosh S
Published: April 2020

Background

Access to screening, brief intervention and referral to treatment programmes for alcohol use have been shown to be effective; however, little is known about access to these services among service members and veterans. We examined the association of service member or veteran rural-dwelling area and the following outcomes: recent general health check-up, alcohol screening and alcohol brief intervention.

Methods

Data on 5080 military service members and veterans were obtained from the 2017 Behavioural Risk Factor Surveillance System of the USA. We estimated rural–urban disparities in the receipt of a recent voluntary general health check-up, as well as the receipt of alcohol screening and brief intervention, using a mixed logit model.

Results

Of the 5080 participants in the study, a total of 4666 (90.49%, 95% CI 89.39% to 91.48%) reported a general health check-up in the last 2 years. Results showed 7.48% of the sample (95% CI 6.64% to 8.41%) exhibited heavy alcohol consumption patterns. Of the 414 participants who did not undergo a general health check-up, 13.80% (95% CI 9.63% to 19.41%) exhibited a pattern of heavy alcohol consumption. Rural individuals were less likely to report a recent health check-up (adjusted OR=0.82, 95% CI 0.79 to 0.87). Rurality was also independently associated with decreased likelihood of receiving an alcohol screening and brief intervention.

Conclusion

Greater access to telehealth or other geographically flexible screening and brief intervention programmes is needed in rural areas for service members and veterans.
Are symptoms of insomnia related to respiratory symptoms? Cross-sectional results from 10 European countries and Australia
Authors: Bjornsdottir Erla , Lindberg Eva , Benediktsdottir Bryndis , Gislason Thorarinn , Garcia Larsen Vanessa , Franklin Karl , Jarvis Debbie , Demoly Pascal , Perret Jennifer L , Garcia Aymerich Judith , Arenas Sandra Dorado , Heinrich Joachim , Torén Kjell , Jögi Rain , Janson Christer
Published: April 2020

Objectives

To compare the prevalence of different insomnia subtypes among middle-aged adults from Europe and Australia and to explore the cross-sectional relationship between insomnia subtypes, respiratory symptoms and lung function.

Design

Cross-sectional population-based, multicentre cohort study.

Setting

23 centres in 10 European countries and Australia.

Methods

We included 5800 participants in the third follow-up of the European Community Respiratory Health Survey III (ECRHS III) who answered three questions on insomnia symptoms: difficulties falling asleep (initial insomnia), waking up often during the night (middle insomnia) and waking up early in the morning and not being able to fall back asleep (late insomnia). They also answered questions on smoking, general health and chronic diseases and had the following lung function measurements: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio. Changes in lung function since ECRHS I about 20 years earlier were also analysed.

Main outcome measures

Prevalence of insomnia subtypes and relationship to respiratory symptoms and function.

Results

Overall, middle insomnia (31.2%) was the most common subtype followed by late insomnia (14.2%) and initial insomnia (11.2%). The highest reported prevalence of middle insomnia was found in Iceland (37.2%) and the lowest in Australia (22.7%), while the prevalence of initial and late insomnia was highest in Spain (16.0% and 19.7%, respectively) and lowest in Denmark (4.6% and 9.2%, respectively). All subtypes of insomnia were associated with significantly higher reported prevalence of respiratory symptoms. Only isolated initial insomnia was associated with lower FEV1, whereas no association was found between insomnia and low FEV1/FVC ratio or decline in lung function.

Conclusion

There is considerable geographical variation in the prevalence of insomnia symptoms. Middle insomnia is most common especially in Iceland. Initial and late insomnia are most common in Spain. All insomnia subtypes are associated with respiratory symptoms, and initial insomnia is also associated with lower FEV1.