bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired liver regeneration and lipid homeostasis in CCl4 treated WDR13 deficient mice
Authors: Mishra Arun Prakash , Siva Archana B , Gurunathan Chandrashekaran , Komala Y , Lakshmi B Jyothi
Published: September 2019

Background and Aim

WDR13 - a WD repeat protein, is abundant in pancreas, liver, ovary and testis. Absence of this protein in mice has been seen to be associated with pancreatic β-cell proliferation, hyperinsulinemia and age dependent mild obesity. Previously, we have reported that the absence of WDR13 in diabetic Leprdb/db mice helps in amelioration of fatty liver phenotype along with diabetes and systemic inflammation. This intrigued us to study direct liver injury and hepatic regeneration in Wdr13−/0 mice using hepatotoxin CCl4.

Methods

Mice were injected with CCl4 twice a week for 8 consecutive weeks. Controls were injected with vehicle (olive oil) similarly. After the last injection, mice were given a 10-days of recovery period and then sacrificed for physiological and molecular analyses.

Results

In the present study we report slower hepatic regeneration in Wdr13−/0 mice as compared to their wild type littermates after CCl4 administration. Interestingly, during the regeneration phase, hepatic hypertriglyceridemia was observed in Wdr13−/0 mice. Further analyses revealed an upregulation of PPAR pathway in the liver of CCl4-administered Wdr13−/0 mice, causing de novo lipogenesis.

Conclusions

The slower hepatic regeneration observed in CCl4 administered Wdr13−/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.
Linker Histone H1 subtypes specifically regulate neutrophil differentiation
Authors: Sollberger Gabriel , Streeck Robert , Caffrey Brian E. , Skoultchi Arthur I. , Zychlinsky Arturo
Published: September 2019

Neutrophils are important innate immune cells that tackle invading pathogens with different effector mechanisms. They acquire this antimicrobial potential during their maturation in the bone marrow, where they differentiate from hematopoietic stem cells in a process called granulopoiesis. Mature neutrophils are terminally differentiated and short-lived with a high turnover rate. Here, we show a critical role for linker histone H1 on the differentiation and function of neutrophils using a genome-wide CRISPR/Cas9 screen in the human cell line PLB-985. We systematically disrupted expression of somatic H1 subtypes to show that individual H1 subtypes affect PLB-985 maturation in opposite ways. Importantly, H1 subtypes also affect neutrophil differentiation of murine bone marrow stem cells, demonstrating an unexpected subtype-specific role for H1 in granulopoiesis.
Local network determinants of spontaneously emerging cortical maps
Authors: Fekete Tomer , Omer David B. , Grinvald Amiram , van Leeuwen Cees
Published: September 2019

Spontaneously emerging cortical maps related to the functional architecture of visual cortex have been observed initially in anesthetized cats and, subsequently, in monkey, albeit only under certain anesthetic regimes, and not in the awake state. Here we propose a network model that can accommodate these diverse findings. The model identifies two crucial determinants for the emergence of spontaneous map-like activity – local balance between excitatory and inhibitory activity, and the strength of feature-specific synaptic connections (e.g. orientation, ocularity). Our model further shows that dynamically, map-like activity patterns could be triggered either by standing or travelling waves, a mode of operation which is determined by the spatial extent of lateral connections within a given network. Our results suggest that careful pharmacological intervention can unveil the prevalence of maps – recurring spatial patterns of inhomogeneous lateral connectivity - in cortex without the need to explicitly identify area specific optimal features.
Transcriptomic profiling of plaque psoriasis and cutaneous T cell subsets during treatment with secukinumab
Authors: Liu Jared , Chang Hsin-Wen , Beck Kristen M. , Sekhon Sahil , Schmidt Timothy H. , Yan Di , Huang Zhi-Ming , Yang Eric J. , Sanchez Isabelle M. , Nakamura Mio , Bhattarai Shrishti , Thibodeaux Quinn , Ahn Richard , Bhutani Tina , Rosenblum Michael D. , Liao Wilson
Published: September 2019

The IL17A inhibitor secukinumab is efficacious for the treatment of psoriasis. In order to define its mechanism of action, it is important to understand its impact on psoriatic whole skin tissue as well as specific skin-resident immune cell populations such as T lymphocytes. In this study, we treated 15 moderate-to-severe plaque psoriasis patients with secukinumab and characterized the longitudinal transcriptomic changes of whole lesional skin tissue and cutaneous CD4+ T effector cells (Teffs), CD4+ T regulatory cells (Tregs), and CD8+ T effector cells during 12 weeks of treatment. Secukinumab was clinically effective, with 100%, 47%, and 27% of patients in the study achieving PASI75, PASI90, and PASI100 by week 12, respectively. At baseline prior to treatment, we observed that IL17A overexpression predominates in psoriatic CD8+ T cells rather than Teffs, supporting the importance of IL-17-secreting CD8+ T cells (Tc17) compared to IL-17-secreting CD4+ T cells (Th17) cells in the pathogenesis of psoriasis. Although secukinumab targets only IL17A, we observed rapid reduction of IL17A, IL17F, IL23A, IL23R, and IFNG expression in lesional skin as soon as 2 weeks after initiation of treatment and normalization of expression by week 12. Secukinumab treatment resulted in resolution of 89-97% of psoriasis-associated expression differences in both bulk tissue and T cell subsets by week 12 of treatment. Overall, secukinumab appears to rapidly reverse many of the molecular hallmarks of psoriasis.
A glycogenin homolog controls Toxoplasma gondii growth via glycosylation of an E3 ubiquitin ligase
Authors: Mandalasi Msano , Kim Hyun W. , Thieker David , Osman Sheikh M. , Gas-Pascual Elisabet , Rahman Kazi , Zhao Peng , Daniel Nitin G. , van der Wel Hanke , Ichikawa H. Travis , Glushka John N. , Wells Lance , Woods Robert J. , Wood Zachary A. , West Christopher M.
Published: September 2019

Skp1, a subunit of E3 Skp1/Cullin-1/F-box protein ubiquitin ligases, is uniquely modified in protists by an O2-dependent prolyl hydroxylase that generates the attachment site for a defined pentasaccharide. Previous studies demonstrated the importance of the core glycan for growth of the parasite Toxoplasma gondii in fibroblasts, but the significance of the non-reducing terminal sugar was unknown. Here, we find that a homolog of glycogenin, an enzyme that can initiate and prime glycogen synthesis in yeast and animals, is required to catalyze the addition of an α-galactose in 3-linkage to the subterminal glucose to complete pentasaccharide assembly in cells. A strong selectivity of the enzyme (Gat1) for Skp1 in extracts is consistent with other evidence that Skp1 is the sole target of the glycosyltransferase pathway. gat1-disruption results in slow growth attesting to the importance of the terminal sugar. Molecular dynamics simulations provide an explanation for this finding and confirm the potential of the full glycan to control Skp1 organization as in the amoebozoan Dictyostelium despite the different terminal disaccharide assembled by different glycosyltransferases. Though Gat1 also exhibits low α-glucosyltransferase activity like glycogenin, autoglycosylation is not detected and gat1-disruption reveals no effect on starch accumulation. A crystal structure of the ortholog from the crop pathogen Pythium ultimum explains the distinct substrate preference and regiospecificity relative to glycogenin. A phylogenetic analysis suggests that Gat1 is related to the evolutionary progenitor of glycogenin, and acquired a role in glycogen formation following the ancestral disappearance of the underlying Skp1 glycosyltransferase prior to amoebozoan emergence.
In situ depth-resolved synchrotron radiation X-ray spectroscopy study of radiation-induced Au deposition
Authors: Chen Guang , Du Yonghua , An Pengfei , Zheng Lirong , Chu Shengqi , Zhang Jing
Published: September 2019

To illustrate the process of synchrotron radiation induced reduction of tetrachloroauric solutions, a confocal synchrotron radiation X-ray spectroscopy experiments system has been introduced to monitor the depth-resolved elemental Au distribution and chemical species during the Au reduction reaction. Combining the results from confocal X-ray spectroscopy with that from X-ray contrast imaging, the mechanism of synchrotron radiation induced Au reduction, along with the process of Au deposition, were proposed. These demonstrations provide novel avenues to spatially resolved analysis of in situ solution radiolysis.
Comparative analysis of sample preparation protocols of soft biological tissues for morphometric studies using synchrotron-based X-ray microtomography
Authors: Dias Carlos Sato Baraldi , Neto Dionísio Pedro Amorim , Baraldi Giovanni Lenzi , Fonseca Matheus de Castro
Published: September 2019

The spread of microtomography as a tool for visualization of soft tissues has had a significant impact on a better understanding of complex biological systems. This technique allows a detailed three-dimensional quantitative view of the specimen to be obtained, correlating its morphological organization with its function, providing valuable insights on the functionality of the tissue. Regularly overlooked, but of great importance, proper sample mounting and preparation are fundamental for achieving the highest possible image quality even for the high-resolution imaging systems currently under development. Here, a quantitative analysis compares some of the most common sample-mounting strategies used for synchrotron-based X-ray microtomography of soft tissues: alcoholic-immersion, paraffin-embedding and critical-point drying. These three distinct sample-mounting strategies were performed on the same specimen in order to investigate their impact on sample morphology regardless of individual sample variation. In that sense, the alcoholic-immersion strategy, although causing less shrinkage to the tissue, proved to be the most unsuitable approach for a high-throughput high-resolution imaging experiment due to sample drifting. Also, critical-point drying may present some interesting advantages regarding image quality but is also incompatible with a high-throughput experiment. Lastly, paraffin-embedding is shown to be the most suitable strategy for current soft tissue microtomography experiments. Such detailed analysis of biological sample-mounting strategies for synchrotron-based X-ray microtomography are expected to offer valuable insights on the best approach for using this technique for 3D imaging of soft tissues and following morphometric analysis.
The effective volumes of waters of crystallization: non-ionic pharmaceutical systems
Authors: Glasser Leslie
Published: September 2019

The physical properties of organic solids are altered when hydrated (and, more generally, when solvated) and this is of particular significance for pharmaceuticals in application; for instance, the solubility of a hydrate is less than that of its parent. The effective volumes of waters of crystallization for non-ionic pharmaceuticals (where the `effective' volume is the difference per water molecule between the hydrate volume and the volume of the anhydrous parent) are here examined. This investigation contrasts with our earlier study of effective volumes of waters of crystallization for ionic materials where the coulombic forces are paramount. Volumetric properties are significant since they correlate strongly with many thermodynamic properties. Twenty-nine hydrate/parent systems have been identified, and their volumetric properties are reported and analysed (apart from aspartame and ephedrine for which the structural data are inconsistent). Among these systems, the data for paracetamol are extensive and it is possible to differentiate among the volumetric properties of its three polymorphs and to quantify the effect of temperature on their volumes. The effective volumes in both ionic and non-ionic systems are similar, with a median effective volume of 22.8 Å3 for the non-ionic systems compared with 24.2 Å3 for the ionic systems, and both are smaller than the molecular volume of 30 Å3 of ambient liquid water – which appears to be an upper limit to the effective volumes of waters of crystallization under ambient conditions. These results will be supportive in checking and confirmation of hydrated crystal structures and in assessing their thermodynamic properties.
Variability aware FinFET SRAM cell with improved stability and power for low power applications
Authors: Birla Shilpi
Published: September 2019

Purpose

Major area of a die is consumed in memory components. Almost 60-70% of chip area is being consumed by “Memory Circuits”. The dominant memory in this market is SRAM, even though the SRAM size is larger than embedded DRAM, as SRAM does not have yield issues and the cost is not high as compared to DRAM. At the same time, the other attractive feature for the SRAM is speed, and it can be used for low power applications. CMOS SRAM is the crucial component in microprocessor chips and applications, and as the said major portion of the area is dedicated to SRAM arrays, CMOS SRAM is considered to be the stack holders in the memory market. Because of the scaling feature of CMOS, SRAM had its hold in the market over the past few decades. In recent years, the limitations of the CMOS scaling have raised so many issues like short channel effects, threshold voltage variations. The increased thrust for alternative devices leads to FinFET. FinFET is emerging as one of the suitable alternatives for CMOS and in the region of memory circuits.

Design/methodology/approach

In this paper, a new 11 T SRAM cell using FinFET technology has been proposed, the basic component of the cell is the 6 T SRAM cell with 4 NMOS access transistors to improve the stability and also makes it a dual port memory cell. The proposed cell uses a header scheme in which one extra PMOS transistor is used which is biased at different voltages to improve the read and write stability thus, helps in reducing the leakage power and active power.

Findings

The cell shows improvement in RSNM (read static noise margin) with LP8T by 2.39× at sub-threshold voltage 2.68× with D6T SRAM cell, 5.5× with TG8T. The WSNM (write static noise margin) and HM (hold margin) of the SRAM cell at 0.9 V is 306 mV and 384  mV. It shows improvement at sub-threshold operation also. The leakage power is reduced by 0.125× with LP8T, 0.022× with D6T SRAM cell, TG8T and SE8T. The impact of process variation on cell stability is also discussed.

Research limitations/implications

The FinFet has been used in place of CMOS even though the FinFet has been not been a matured technology; therefore, pdk files have been used.

Practical implications

SRAM cell has been designed which has good stability and reduced leakage by which we can make an array and which can be used as SRAM array.

Social implications

The cell can be used for SRAM memory for low power consumptions.

Originality/value

The work has been done by implementing various leakage techniques to design a stable and improved SRAM cell. The advantage of this work is that the cell has been working for low voltage without degrading the stability factor.
Study on curved surface design of sliding pair based on stepped topography model
Authors: Wu Zhenpeng , Nguyen Vanliem , Zhang Zhihong , Zeng Liangcai
Published: September 2019

Purpose

The stepped topography of the friction pairs mainly causes the fluid film thickness to change in the direction of motion. In this region, there have very few topographical design methods for continuous or non-linear distribution of the fluid film. The purpose of this study is to analyze the effect of the curved surface on the performance of the liquid film.

Design/methodology/approach

First, a numerical simulation is used to solve the optimal bearing capacity and friction coefficient of the liquid film under the condition of the minimum film thickness. Then, the curved surface described by the sinusoidal curve equation is applied in the transitional region of maximum and minimum film thickness. The bearing capacity and the friction coefficient of the liquid film are respectively simulated and compared in the same condition of the minimum film thickness.

Findings

The research results show that the liquid film using the curved surface transition model, the optimal bearing capacity is significantly increased by 32 per cent while the optimal friction coefficient is clearly reduced by 38 per cent in comparison with using stepped surface model.

Originality/value

The friction pair with curved transition enables better lubrication performance of the liquid film and better adaptability under unstable conditions.
Effect of percolation on hydrodynamic lubrication of rough bilayer porous bearing with circular contact
Authors: Zhang Guotao , Tong Baohong , Yang Shubao , Shi Liping , Yin Yanguo
Published: September 2019

Purpose

The purpose of this paper was to study the hydrodynamic lubrication of rough bilayer porous bearing to reveal the effect of percolation.

Design/methodology/approach

The seepage lubrication model of the circular bilayer porous bearing was established in polar coordinates. The digital filtering technique and Darcy’s law were used to simulate the rough surface and the percolation characteristic of the oil bearing, respectively. The influence of the structural parameters on the lubrication performance was analyzed.

Findings

Compared with the ordinary monolayer oil bearing with high porosity, the bilayer bearing can reduce the whole porosity, prevent oil infiltrating into the porous medium and have better lubrication performance. The lubrication performance of bilayer oil bearing is better than that of the single-layer oil bearing which has a higher porosity. With increasing root-mean-square roughness or decreasing surface porosity, the lubrication performance of the bilayer bearing improves. The lower the porosity of the surface layer, the better the lubrication performance.

Originality/value

This research provides a theoretical basis for clarifying the lubrication mechanism and influence the mechanism of the bilayer oil bearing.
Effects of privacy policy visualization on users’ information privacy awareness level
Authors: Soumelidou Aikaterini , Tsohou Aggeliki
Published: September 2019

Purpose

The purpose of this paper is to propose visualization techniques as a new representation for privacy policies instead of traditional textual representation and to examine empirically their effects on users’ information privacy awareness level.

Design/methodology/approach

The authors selected as a case the privacy policy of Instagram and conducted two empirical investigations, each one with three interventions and each representing a different version of the Instagram privacy policy to users. Through a pre- and a post-questionnaire, the authors examined the effects that each representation technique had on the users’ privacy awareness level.

Findings

The paper finds that visualized privacy policies lead to higher privacy awareness levels than conventional textual ones, especially when icons are included.

Research limitations/implications

The authors implemented two new representation techniques offering beneficial guidelines for designing more attractive privacy policy representations. However, the samples are rather limited for generalization to the wide population; nonetheless, they are significant to demonstrate the effect of visualized techniques. The findings might also be subject to bias (e.g. brand bias), although the authors took necessary methodological actions to prevent bias.

Practical implications

The results and the methodology of the paper could guide practitioners for the representation of a privacy policy, given that the authors provide systematic and concrete steps.

Originality/value

This paper examines the value of privacy policy visualization as a new approach for enabling user privacy awareness, as well as implements two visualization techniques for a given privacy policy. The paper and its findings should be useful for researchers, as well as for practitioners.
Investigation of crack in beams using anti-resonance technique and FEA approach
Authors: Bhaurkar Vyankatesh Prabhakar , Thakur Ajaykumar Gulabsing
Published: September 2019

Purpose

In the case of machines, structures and assemblies, the crack generation and propagation is becoming a great concern, especially in airplane wings, turbine blades and such other applications. This is because these parts are very large in size and the crack size is very small, i.e. in microns. Hence, there is an important need to locate the crack and to find its severity before it starts to propagate and also to detect these parameters by on-site non-destructive testing methods. This paper aims to develop and test the methodology to locate an unknown single open crack in steel cantilever beam along with its severity.

Design/methodology/approach

This study covers analytical, numerical and experimental analysis for healthy and cracked beams. Vibration-based approach and finite element analysis (FEA) approach is used for analytical and numerical study respectively. Own designed and dedicated experimental set-up is used for testing purpose along with fast fourier transform analyzer. An anti-resonance technique is used to locate and to find the severity of unknown crack. The statistical approach helps to validate the results.

Findings

The comparison of the natural frequency of healthy and cracked steel cantilever beam shows that the crack in the beam reduces its natural frequency. The accuracy of results is achieved by finding actual density and Young's modulus of steel specimen under consideration. It is helpful to verify the health of the non-cracked beam by applying dye testing. The study of natural frequency and anti-resonance gives the location of crack and its depth also. The FEA approach proved to be an important tool for numerical analysis of cracked beam.

Research limitations/implications

The research is limited to steel material and surface cracks only.

Practical implications

Practically, this study highlights how to locate a surface crack in steel beam along with its depth, i.e. severity with great accuracy. Identification of the factors such as location and depth of a crack provide the severity of damage in airplane wings, turbine blades, bridges and many more, and thereby, it helps in safety at working vicinity.

Social implications

The identification and solutions of current research helps to predict the operational life of machine elements such as airplane wings, turbine blades, bridges and many more, and thereby, it helps in the safety of people in working vicinity of such structures.

Originality/value

The work presented, is based on original research and experimentation. This work is valued contribution in the field of methodologies applied for fault detection in structures and also determining its correctness by numerical and experimental work.
Sharia motivation in Muslim tourism definition, is it matter?
Authors: Usman Hardius , Sobari Nurdin , Sari Lia Estika
Published: September 2019

Purpose

This study aims to identify the terminology that is in accordance with the reality of Muslim tourism market, especially from the perspective of Sharia motivation, between Halal tourism and Islamic tourism; provide information on the special needs of Muslim travelers based on the dominant motivational differences; and find the impact of Sharia motivation and the special needs of Muslim tourists to their satisfaction.

Design/methodology/approach

The target population in this study is Muslim traveler at least 18 years old who has been traveling throughout Indonesia. Paired samplet-Test, multivariate analysis of variance and the multiple linier regression are applied for data analysis.

Findings

This study finds that Sharia motivation is less dominant in encouraging Muslims to travel; Sharia motivation has no impact on the importance of Sharia transportation, generic transportation and generic activities; and the dominance of Sharia motivation does not affect Muslim tourist satisfaction. However, the dominance of Sharia motivation has an influence on the importance of Sharia accommodation and Sharia activities, where both variables have positive effect on satisfaction. In the end, this study concludes that it is better to use the concept of Halal tourism than Islamic tourism.

Originality/value

This paper investigates the term of Halal tourism and Islamic tourism that are still ambiguous; even some researchers consider that the definition of both is similar.
Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti‐topoisomerase I‐positive systemic sclerosis‐associated interstitial lung disease
Authors: Ebata Satoshi , Yoshizaki Ayumi , Fukasawa Takemichi , Miura Shunsuke , Takahashi Takehiro , Sumida Hayakazu , Asano Yoshihide , Sato Shinichi
Published: September 2019

Systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) is the most frequent cause of death for SSc but there is still no sufficient treatment available. Although cyclophosphamide (CYC) therapy is a common treatment which has shown statistical efficacy against SSc‐ILD to date, its effects are temporary and not enough. Rituximab (RTX), the anti‐CD20 monoclonal antibody, has recently shown efficacy in many autoimmune diseases. In SSc‐ILD, RTX is also considered to be one of the novel treatment candidates. However, studies of SSc‐ILD in Japanese treated with RTX have only a few case reports. Therefore, in this study, we retrospectively compared nine patients treated with RTX and 30 patients treated with CYC to investigate the efficacy of RTX treatment for Japanese anti‐topoisomerase I‐positive SSc‐ILD patients. At the 24‐month evaluation, the improvement rates of percent predicted of forced vital capacity and percent predicted of diffusing capacity of the lung carbon monoxide in the RTX‐treated group were significantly higher than those in the CYC‐treated group (20.6 ± 8.8% vs 1.1 ± 3.9%; P < 0.05 and 34.0 ± 6.0% vs −1.5 ± 2.8%; P < 0.01, respectively). In addition, skin thickness scores also showed a marked improvement from 13.5 points before the start of treatment to 5.8 points after 24 months by RTX therapy (P < 0.05). These results suggest that RTX treatment is more effective for Japanese SSc‐ILD patients than CYC treatment. In the future, it is expected that large‐scale clinical trials will show the usefulness of RTX treatment for SSc‐ILD.
The global distribution and evolutionary history of the pT26‐2 archaeal plasmid family
Authors: Badel Catherine , Erauso Gaël , Gomez Annika L. , Catchpole Ryan , Gonnet Mathieu , Oberto Jacques , Forterre Patrick , Da Cunha Violette
Published: September 2019

Although plasmids play an important role in biological evolution, the number of plasmid families well‐characterized in terms of geographical distribution and evolution remains limited, especially in archaea. Here, we describe the first systematic study of an archaeal plasmid family, the pT26‐2 plasmid family. The in‐depth analysis of the distribution, biogeography and host–plasmid co‐evolution patterns of 26 integrated and 3 extrachromosomal plasmids of this plasmid family shows that they are widespread in Thermococcales and Methanococcales isolated from around the globe but are restricted to these two orders. All members of the family share seven core genes but employ different integration and replication strategies. Phylogenetic analysis of the core genes and CRISPR spacer distribution suggests that plasmids of the pT26‐2 family evolved with their hosts independently in Thermococcales and Methanococcales, despite these hosts exhibiting similar geographic distribution. Remarkably, core genes are conserved even in integrated plasmids that have lost replication genes and/or replication origins suggesting that they may be beneficial for their hosts. We hypothesize that the core proteins encode for a novel type of DNA/protein transfer mechanism, explaining the widespread oceanic distribution of the pT26‐2 plasmid family.
Refining the prognosis of fetuses infected with Cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: a single‐centre retrospective study
Authors: Faure‐Bardon V , Millischer A‐E , Deloison B , Sonigo P , Grévent D , Salomon L , Stirnemann J , Nicloux M , Magny J‐F , Leruez‐Ville M , Ville Y
Published: September 2019

Objective

To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT).

Design

A retrospective study.

Setting

Reference fetal medicine unit.

Population

Sixty‐two fetuses infected <14 weeks of gestation.

Methods

We defined second‐trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA.

Main outcome measures

For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow‐up were reported.

Results

The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false‐positive findings at MRI were mostly the result of hypersignals of white matter.

Conclusions

Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy.

Tweetable abstract

Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks.
Methylation‐Based Age Prediction Using Pyrosequencing Platform from Seminal Stains in Han Chinese Males
Authors: Li Luyao , Song Feng , Lang Min , Hou Jiayi , Wang Zheng , Prinz Mechthild , Hou Yiping
Published: September 2019

Various methods have been performed to predict an unknown individual's age from biological traces in forensic investigations. A considerably accurate age prediction for the semen donor can help narrow down the search in a sexual assault case. The aim of this study was to develop an assay for age prediction from seminal stains in Han Chinese males. We built a sperm‐specific linear regression model using bisulfite pyrosequencing. Validations were conducted with a Mean Absolute Deviation from the chronological age (MAD) of 4.219 years in liquid semen, 4.158 years in fresh seminal stains, 4.393 years in aged seminal stains, and 3.880 years in mixed stains, respectively. Furthermore, our strategy enables accurate age prediction using a forensic casework sample. The strategy indicated that we produced an accurate and reliable age prediction tool for the semen donors in Han Chinese males for forensic purposes.
Impact of early nausea on varenicline adherence and smoking cessation
Authors: Peng Annie R. , Swardfager Walter , Benowitz Neal L. , Ahluwalia Jasjit S. , Lerman Caryn , Nollen Nicole L. , Tyndale Rachel F.
Published: September 2019

Background and aims

Varenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible effect of nausea on smoking cessation outcomes mediated by adherence.

Design

Mediation path analysis.

Setting

Multiple sites within Canada and the United States.

Participants

Treatment‐seeking smokers receiving varenicline from two smoking cessation clinical trials: Quit2Live (NCT01836276; n = 449) and Pharmacogenetics of Nicotine Addiction Treatment (PNAT) (NCT01314001; n = 421).

Measurements

Nausea severity was collected through self‐report and adherence was biologically assessed using varenicline concentrations (Quit2Live, plasma sample at week 4; PNAT, saliva sample at week 2). In Quit2Live, the end‐points were cotinine‐verified abstinence at weeks 4, 12 and 26. In PNAT, the end‐points were carbon monoxide‐verified abstinence at weeks 2, 12 and 26.

Findings

Early nausea was not directly associated with abstinence [odds ratio (OR) ranging from 0.73–1.28; P ≥ 0.26]. However early nausea was indirectly associated with lower cessation rates at multiple timepoints (ORs ranging from 0.92–0.94; 95% CI between 0.83–0.99) in a relationship mediated by reduced varenicline adherence (assessed by plasma varenicline concentrations) in the primary trial (Quit2Live). This relationship between nausea, adherence and cessation was similar in direction but weaker in effect size (ORs ranging from 0.98–0.99; 95% CI between 0.90–1.03) in a secondary trial (PNAT), where adherence was assessed using salivary varenicline concentrations.

Conclusions

These data suggest that early nausea during varenicline treatment may be indirectly associated with lower likelihood of smoking cessation through reducing varenicline adherence. Differences in robustness between the trials may be due to the different biological matrices (plasma vs. saliva) and/or timing used to assess varenicline adherence. The results of the first study suggest that improved management of early nausea during varenicline treatment may positively impact smoking cessation success through increasing varenicline adherence.
Late‐onset hypogonadism: metabolic impact
Authors: Grossmann M. , Ng Tang Fui M. , Cheung A. S.
Published: September 2019

Background

Obesity and dysglycemia (comprising insulin resistance, the metabolic syndrome and type 2 diabetes), that is diabesity, are associated with reduced circulating testosterone and, in some men, clinical features consistent with androgen deficiency.

Objective

To review the metabolic impact of late‐onset hypogonadism.

Methods

Comprehensive literature search with emphasis on recent publications.

Results

Obesity is one of the strongest modifiable risk factors for late‐onset hypogonadism, and coexisting diabetes leads to further hypothalamic‐pituitary‐testicular axis suppression. The hypothalamic‐pituitary‐testicular axis suppression is functional and hence potentially reversible, and occurs predominantly at the level of the hypothalamus. While definitive mechanistic data are lacking, the evidence suggests that hypothalamic‐pituitary‐testicular axis suppression is mediated by dysregulation of pro‐inflammatory cytokines leading to hypothalamic inflammation. Dysregulation of central leptin and insulin signaling may also contribute. In contrast, recent data challenge the paradigm that estradiol excess is a major contributor to hypothalamic‐pituitary‐testicular axis suppression. Instead, relative estradiol signaling deficiency may contribute to metabolic dysregulation in men with diabesity. While weight loss and optimization of comorbidities can reverse functional hypothalamic‐pituitary‐testicular axis suppression, testosterone treatment leads to metabolically favorable changes in body composition and to improvements in insulin resistance.

Discussion

The relationship between diabesity and late‐onset hypogonadism is bidirectional. Preliminary evidence suggests that, in carefully selected men, lifestyle measures and testosterone treatment may have additive effects.

Conclusions

While recent research has provided new insights into mechanistic and clinical aspects of diabesity‐associated late‐onset hypogonadism, more evidence from well‐designed large trials is needed to guide the optimal clinical approach to such men.
Narratives of Transfer, Dependence, and Resistance: Rastafarian Perspectives on US Colonialism in the Virgin Islands
Authors: Benard Akeia A. F.
Published: September 2019

In 1917, the United States purchased the Virgin Islands—and the people living on them—for $25 million from Denmark. The US Virgin Islands is currently one of 16 remaining non‐self‐governing territories in the world. This political (and necessarily) economic status is fundamentally identical to the “colony.” The territorial status of the Virgin Islands severely hampers the human rights and social, economic, and political potential and autonomy of the dependents of the Virgin Islands. My work focuses on the ways in which Rastafarians on St. Croix, USVI resist, negotiate, accommodate, and internalize their dependent territorial status and the ways in which they critique Western cultural, economic, and political imperialism through historical narrative, personal history, and political commentary during ritual reasonings or sessions. Much of the following article is in narrative form, so that Rastas can speak on colonialism and hegemony in their own words.
Emotions of Felt Memories: Looking for Interplay of Emotions and Histories in Iranian Political Consciousness Since Iran–Iraq War (1980–1988)
Authors: Saramifar Younes
Published: September 2019

Emotions and feelings overwhelm mnemonic practices of any collective with traces of violence in its history. The violent history has become the means for the Iranian regime to regulate the nation's political consciousness. The regime formulates the political consciousness by way of politics of memory and enforcing a master narrative drawn from Shi'i history. I trace elicited emotions, within the war veterans’ memoirs, to explain feelings and consciousness in the realm of situated bodies. By way of those emotions, the article outlines an anthropology of emotions that rejects universal codes of emotions and instead proposes following an embodied consciousness through emotions along with histories that evoke them. My argument broadens Sarah Ahmed's idea of history and emotions to arrive at the assemblage of mnemonic practices in post‐war Iran and advocate a historically informed anthropology of emotions.
Low physical activity and higher use of screen devices are associated with myopia at the age of 16‐17 years in the CCC2000 Eye Study
Authors: Hansen Mathias Hvidtfelt , Laigaard Poul Pedersen , Olsen Else Marie , Skovgaard Anne Mette , Larsen Michael , Kessel Line , Munch Inger Christine
Published: September 2019

Purpose

To determine the myopia prevalence in a Danish cohort aged 16–17 years and its relation to physical activity and use of screen‐based electronic devices.

Methods

The Copenhagen Child Cohort 2000 Eye Study is a prospective, population‐based, observational study. Information about use of screen devices and physical activity was obtained using questionnaires. Myopia was defined as non‐cycloplegic subjective spherical equivalent refraction ≤−0.50 D in right eye.

Results

We included 1443 participants (45% boys) with a median age (±IQR) of 16.6 years (±0.3). The prevalence of myopia was 25% (CI95% 23–28, n = 360) with no differences between sexes (p = 0.10).

The odds ratio (OR) for myopia was 0.57 (CI95% 0.42–0.76, p = 0.0002) in participants physically active 3–6 hr/week (n = 502) and 0.56 (CI95% 0.42–0.76, p = 0.0002) if active >6 hr/week (n = 506), both compared with participants physically active <3 hr/week (n = 396).

The use of screen devices >6 hr/day was associated with increased OR for myopia compared with screen device use <2 hr/day in both weekdays (OR = 1.95, CI95% 1.16–3.30, p = 0.012) and weekends (OR = 2.10, CI95% 1.17–3.77, p = 0.013).

Conclusion

In this cohort of healthy 16–17‐year olds, lower physical activity and more use of screen devices contributed significantly to the observed 25% prevalence of myopia with a roughly doubled risk of having myopia if physically active <3 hr/week or if using screen devices >6 hr/day. Our results support physical activity being a protective factor and near work a risk factor for myopia in adolescents.
Prevalence of macular complications related to myopia – Results of a multicenter evaluation of myopic patients in eye clinics in France
Authors: Leveziel Nicolas , Marillet Simon , Dufour Quentin , Lichtwitz Olivier , Bentaleb Yacine , Pelen François , Ingrand Pierre , Bourne Rupert
Published: September 2019

Purpose

Uncorrected refractive errors are the first cause of vision impairment worldwide. High myopia is a frequent cause of sight‐threatening chorioretinal complications. The aim of this study was to evaluate the prevalence of macular complications, visual impairment and blindness in patients with myopia.

Methods

A cross‐sectional multicenter study carried out in French eye clinics mainly dedicated to refractive errors. Myopia severity was defined as mild (−0.5 to −3 D), moderate (−3 to −6 D), high (−6 to −10 D) and very high (more than −10 D). Macular complications related to myopia included lacquer cracks, myopic choroidal neovascularization, chorioretinal atrophy and retinoschisis. The prevalences of macular complications, blindness and vision impairment were estimated with respect to degree of myopia and age. Eligibility criteria were myopia on the left eye of −0.5 D or more. Exclusion criteria included any missing data related to subjective refractive error, age, gender and any history of cataract or refractive surgery.

Results

Data files from 198 641 myopic individuals with a mean age of 34 years (SD: 15 years) were analysed. The prevalence of mild, moderate, high and very high myopia was, respectively, 65.95%, 26.14%, 6.72% and 1.19%. The prevalence of macular complications in the high and very high myopia groups was 0.5% [0.39–0.64] and 4.27% [3.49–5.17]. The prevalence of blindness or vision impairment was observed in 10.10% [8.91–11.39%] of the very high myopic group. At 60 years old or over, the prevalences of blindness or vision impairment were, respectively, 9.75% [7.91–11.85%] and 25.71% [21.00–30.87%] in the high and very high myopia groups.

Conclusions

This multicenter cross‐sectional study provides new insights in terms of prevalence of macular complications related to myopia. To our knowledge, this is one of the largest European studies focusing on individuals with myopia, particularly on the macular complications and the functional consequences in relation to myopia.
Shiga toxin 2eB‐transgenic lettuce vaccine is effective in protecting weaned piglets from edema disease caused by Shiga toxin‐producing Escherichia coli infection
Authors: Hamabata Takashi , Sato Toshio , Takita Eiji , Matsui Takeshi , Imaoka Taishi , Nakanishi Nobuo , Nakayama Keizo , Tsukahara Takamitsu , Sawada Kazutoshi
Published: September 2019

Porcine edema disease (ED) is a toxemia that is caused by enteric infection with Shiga toxin 2e (Stx2e)‐producing Escherichia coli (STEC) and is associated with high mortality. Since ED occurs most frequently during the weaning period, preweaning vaccination of newborn piglets is required. We developed stx2eB‐transgenic lettuce as an oral vaccine candidate against ED and examined its protective efficacy using a piglet STEC infection model. Two serially developed Stx2eB‐lettuce strains, 2BN containing ingredient Stx2eB constituting a concentration level of 0.53 mg Stx2eB/g of powdered lettuce dry weight (DW) and 2BH containing ingredient Stx2eB constituting a concentration level of 2.3 mg of Stx2eB/g of powdered lettuce DW, were evaluated in three sequential experiments. Taken the results together, oral administration of Stx2eB‐lettuce vaccine was suggested to relieve the pathogenic symptoms of ED in piglets challenged with virulent STEC strain. Our data suggested that Stx2eB‐lettuce is a promising first oral vaccine candidate against ED.
What determines the sustainability of community‐based palliative care operations? Perspectives of the social work professionals
Authors: Abdul Azeez E.P. , Anbu Selvi G.
Published: September 2019

The palliative care services are least operational in India with exception to the State of Kerala where the movement is widespread. Kerala's model of palliative care is known for its community‐based approach and efforts in universalizing the access. This model is unique in the domains of sustainability and mode of interventions. Cognate to the palliative care interventions worldwide, social workers play a crucial role in the service delivery of palliative care interventions in Kerala too. In this context, the present study attempted to explore the determinants of sustainable community‐based palliative care operations from the perspectives of professional social workers. The study adopted a descriptive qualitative research design using an in‐depth interview method. Interviews were conducted with 12 professional social workers engaged in community‐based palliative care delivery in the northern and central region of Kerala, India. The interviews were audio‐taped, transcribed, and further analyzed applying thematic analysis method. Five major themes, holistic care, community participation, volunteerism, resource mobilization, and socio‐political environment, were emerged from the data manifesting as the determinants of successful palliative care interventions. The result of the study has implications for the policymakers, public health professionals, and social workers who are involved in the development of similar models.
A novel direct method to determine adherence to atorvastatin therapy in patients with coronary heart disease
Authors: Kristiansen Oscar , Vethe Nils T. , Fagerland Morten W. , Bergan Stein , Munkhaugen John , Husebye Einar
Published: September 2019

Aims

Objective methods to monitor statin adherence are needed. We have established a liquid chromatography–tandem mass spectrometry assay for quantification of atorvastatin and its metabolites in blood. This study aimed to develop an objective drug exposure variable with cut‐off values to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease.

Methods

Twenty‐five patients treated with atorvastatin 10 mg (n = 5), 20 mg (n = 6), 40 mg (n = 7) and 80 mg (n = 7) participated in a directly observed atorvastatin therapy study to confirm baseline adherence. After the directly observed therapy, half of the patients (test group) were instructed to stop taking atorvastatin and return for blood sample collection the subsequent 3 days. Levels of atorvastatin and metabolites were compared between the test group and the adherent control group.

Results

The sum of parent drug and all measured primary metabolites correlated well with the atorvastatin dose administered (Spearman's rho = 0.71, 95% CI 0.44–0.87). The dose‐normalized atorvastatin plus metabolites concentrations completely separated the partially adherent test group from the controls at 0.18 nM/mg after 3 days without atorvastatin. To reduce the risk of misinterpreting adherent patients as partially adherent, a corresponding cut‐off at 0.10 nM/mg is proposed. A metabolite level of 2‐OH atorvastatin acid <0.014 nmol/L provided the optimal cut‐off for nonadherence.

Conclusion

A direct method to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease has been developed. This tool may be important for novel studies on adherence and potentially useful in clinical practice.