bluuebunny/crossref_metadata_2025 huggingface dataset:
Recovery of regional systolic and diastolic myocardial function after acute myocardial infarction evaluated by two‐dimensional speckle tracking echocardiography
Authors: Wdowiak‐Okrojek Katarzyna , Wejner‐Mik Paulina , Kasprzak Jarosław D. , Lipiec Piotr
Published: November 2018

Purpose

The assessment of temporal changes in systolic and diastolic regional left ventricle function by two‐dimensional speckle tracking echocardiography (STE) after successful reperfusion therapy of acute myocardial infarction (AMI).

Methods

A total of 97 consecutive patients admitted with AMI and treated with successful percutaneous coronary intervention were included in this study. On days 1, 2, 3, 7, 30 and 180 following admission patients underwent transthoracic echocardiography with subsequent measurement of systolic longitudinal strain (SLS), systolic longitudinal strain rate (SRS) and early diastolic longitudinal strain rate (SRe) in left ventricular segments by speckle tracking technique.

Results

The largest increase in regional SLS and SRS was observed between day 1 and 2. On days 3, 7, 30 and 180 further improvement was noticeable, but the changes were less significant. The highest prognostic value among STE parameters for predicting systolic function recovery after 6‐month‐long follow‐up was achieved by measuring SLS on day 3 (area under the curve = 0·878).

Conclusions

The most of regional systolic function recovery occurs within the first 2 days. The recovery of regional diastolic function takes longer – the most significant part of improvement occurs within the first 7 days. STE parameters have prognostic value for predicting the improvement of systolic function after 180 days.
Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measured by 18F‐fluorodeoxyglucose‐positron emission tomography
Authors: Prando Silvana , Carneiro Camila de Godoi , Otsuki Denise Aya , Sapienza Marcelo Tatit
Published: November 2018

The aim of the present study was to investigate changes in glucose metabolism in male Wistar rats induced by the anesthetics isoflurane and ketamine combined with xylazine via 18F‐fluorodeoxyglucose‐positron emission tomography. We analyzed the differential effects of the anesthetics on 18F‐fluorodeoxyglucose uptake and pharmacokinetics in 33 rats using quantification methods: (a) the standardized uptake value, (b) voxel‐based analyses, and (c) kinetic analysis. Both anesthetics reduced glucose uptake in the entire brain. The voxel‐based analyses detected smaller uptake reductions in the bilateral primary somatosensory system cortex and part of the limbic system in the ketamine‐xylazine (KX) group and in the vestibular nucleus in the isoflurane group. Through kinetic analysis, we found that the volume of distribution and the membrane transport rate K1 were reduced in the KX group. Through various methods of 18F‐fluorodeoxyglucose‐positron emission tomography quantification, the present study found that anesthesia with the ketamine‐xylazine combination induced a global reduction of glucose metabolism compared with isoflurane; this reduction of metabolism was relatively lower in the primary somatosensory cortex and part of the limbic system. The volume of distribution of 18F‐fluorodeoxyglucose and its Glut1‐mediated transport across the brain membranes (K1) were decreased in the KX group.
Circadian disruption: What do we actually mean?
Authors: Vetter Céline
Published: November 2018

The circadian system regulates physiology and behavior. Acute challenges to the system, such as those experienced when traveling across time zones, will eventually result in re‐synchronization to local environmental time cues, but this re‐synchronization is oftentimes accompanied by adverse short‐term consequences. When such challenges are experienced chronically, adaptation may not be achieved, as for example in the case of rotating night shift workers. The transient and chronic disturbance of the circadian system is most frequently referred to as “circadian disruption”, but many other terms have been proposed and used to refer to similar situations. It is now beyond doubt that the circadian system contributes to health and disease, emphasizing the need for clear terminology when describing challenges to the circadian system and their consequences. The goal of this review is to provide an overview of the terms used to describe disruption of the circadian system, discuss proposed quantifications of disruption in experimental and observational settings with a focus on human research, and highlight limitations and challenges of currently available tools. For circadian research to advance as a translational science, clear, operationalizable, and scalable quantifications of circadian disruption are key, as they will enable improved assessment and reproducibility of results, ideally ranging from mechanistic settings, including animal research, to large‐scale randomized clinical trials.
Distinct effects of (R)‐modafinil and its (R)‐ and (S)‐fluoro‐analogs on mesolimbic extracellular dopamine assessed by voltammetry and microdialysis in rats
Authors: Keighron Jacqueline D. , Giancola JoLynn B. , Shaffer Rachel J. , DeMarco Emily M. , Coggiano Mark A. , Slack Rachel D. , Newman Amy Hauck , Tanda Gianluigi
Published: November 2018

Psychostimulant use disorders remain an unabated public health concern worldwide, but no FDA approved medications are currently available for treatment. Modafinil (MOD), like cocaine, is a dopamine reuptake inhibitor and one of the few drugs evaluated in clinical trials that has shown promise for the treatment of cocaine or methamphetamine use disorders in some patient subpopulations. Recent structure–activity relationship and preclinical studies on a series of MOD analogs have provided insight into modifications of its chemical structure that may lead to advancements in clinical efficacy. Here, we have tested the effects of the clinically available (R)‐enantiomer of MOD on extracellular dopamine levels in the nucleus accumbens shell, a mesolimbic dopaminergic projection field that plays significant roles in various aspects of psychostimulant use disorders, measured in vivo by fast‐scan cyclic voltammetry and by microdialysis in Sprague‐Dawley rats. We have compared these results with those obtained under identical experimental conditions with two novel and enantiopure bis(F) analogs of MOD, JBG1‐048 and JBG1‐049. The results show that (R)‐modafinil (R‐MOD), JBG1‐048, and JBG1‐049, when administered intravenously with cumulative drug‐doses, will block the dopamine transporter and reduce the clearance rate of dopamine, increasing its extracellular levels. Differences among the compounds in their maximum stimulation of dopamine levels, and in their time course of effects were also observed. These data highlight the mechanistic underpinnings of R‐MOD and its bis(F) analogs as pharmacological tools to guide the discovery of novel medications to treat psychostimulant use disorders.
Parallel learning processes of a visuomotor adaptation task in a changing environment
Authors: Mariman Juan J. , Burgos Pablo , Maldonado Pedro E.
Published: November 2018

During the control of reaching movements, a key contribution of the visual system is the localization of relevant environmental targets. In motor adaptation processes, the visual evaluation of effector motor behavior enables learning from errors, which demands continuous visual attentional focus. However, most current adaptation paradigms include static targets; therefore, when a learning situation develops in a highly variable environment and there is a double demand for visual resources (environment and motor performance), the evolution of learning processes is unknown. In order to understand how learning processes evolve in a variable environment, a video game task was designed in which subjects were asked to manage a 60° counterclockwise‐rotated cursor to capture descending targets with initially unpredictable trajectories. During the task, the cursor and eye movements were recorded to dissect visuomotor coordination. We observed that the pursuit of the targets conditioned a predominant and continuous visual inspection of the environment instead of the rotated cursor. As learning progressed, subjects exhibited a linear reduction in directional error and selected a motor strategy based on the degree of reward, which improved the performance. These results suggest that when the environment demands high visual attention, error‐based and reinforced motor learning processes are implemented simultaneously, thus enabling efficient predictive behavior.
Circuit development in the master clock network of mammals
Authors: Carmona‐Alcocer Vania , Rohr Kayla E. , Joye Deborah A. M. , Evans Jennifer A.
Published: November 2018

Daily rhythms are generated by the circadian timekeeping system, which is orchestrated by the master circadian clock in the suprachiasmatic nucleus (SCN) of mammals. Circadian timekeeping is endogenous and does not require exposure to external cues during development. Nevertheless, the circadian system is not fully formed at birth in many mammalian species and it is important to understand how SCN development can affect the function of the circadian system in adulthood. The purpose of the current review is to discuss the ontogeny of cellular and circuit function in the SCN, with a focus on work performed in model rodent species (i.e., mouse, rat, and hamster). Particular emphasis is placed on the spatial and temporal patterns of SCN development that may contribute to the function of the master clock during adulthood. Additional work aimed at decoding the mechanisms that guide circadian development is expected to provide a solid foundation upon which to better understand the sources and factors contributing to aberrant maturation of clock function.
Reason unbound: Kant's theory of regulative principles
Authors: Walden Kenneth
Published: November 2018

It is an essential part of Kant's conception of regulative principles and ideas that those principles and ideas are in a certain sense indeterminate. The relevant sense of indeterminacy is cashed out in a section in the Antinomies where Kant says that the regress of conditions of experience forms not a “regressus in infinitum” but a “regressus in indefinitum.” The mathematics that Kant appears to rely on in making this distinction turns out to be problematic, as Jonathan Bennett showed long ago. But I suggest that despite this, there is another mathematically legitimate way to make Kant's point, one enunciated by, among others, Michael Dummett. This reading is corroborated, I suggest, by Kant's conception of reason as a radically open‐ended endeavor.
Past is prologue: host community assembly and the risk of infectious disease over time
Authors: Halliday Fletcher W. , Heckman Robert W. , Wilfahrt Peter A. , Mitchell Charles E.
Published: November 2018

Infectious disease risk is often influenced by host diversity, but the causes are unresolved. Changes in diversity are associated with changes in community structure, particularly during community assembly; therefore, by incorporating change over time, host community assembly may provide a framework to resolve causation. In turn, community assembly can be driven by many processes, including resource enrichment. To test the hypothesis that community assembly causally links host diversity to future disease, we experimentally manipulated host diversity and resource supply to hosts, then allowed communities to assemble for 2 years (surveyed 2012–2014). Initially, host diversity increased disease. Subsequently, host diversity did not directly alter disease. However, host diversity determined the trajectory of host community assembly, altering colonisation by exotic host species and richness‐independent host phylogenetic diversity, which together reversed the initial increase in disease. Ultimately, incorporating the temporal dimension of community assembly revealed novel mechanisms linking host diversity to future disease.
Perceived Collective Efficacy and Parenting Competence: The Roles of Quality of Life and Hope
Authors: Davidson Arad Bilha , McLeigh Jill D. , Katz Carmit
Published: November 2018

Parents' perceptions of their parenting competence predict successful implementation of parenting tasks and contribute to their interest and involvement in parenting and to their children's development. Thus, identifying factors that contribute to parents' perceptions of parenting competence can help inform efforts to promote children's safety and well‐being. The present study employs social disorganization theory to examine the relationship between collective efficacy and parents' sense of competence, measured along two dimensions: parental efficacy and parental satisfaction. It examines the direct association between the two constructs and whether the association is mediated by parent perceptions of their quality of life (QOL) and sense of hope. Data were collected from 198 parents residing in a neighborhood in southern Tel Aviv, Israel. The analyses indicated that high collective efficacy was directly associated with high parental efficacy, but not with high parental satisfaction. Using structural equation modeling, a mediation model was found whereby higher collective efficacy was associated with (a) higher QOL, which in turn was related to a greater sense of hope, which was linked with higher parental efficacy; and (b) higher QOL, which was directly associated with higher parental satisfaction. The findings provide further support to the idea that neighborhood characteristics play an important role in parents' ability to care for their children.
Long‐term safety and efficacy of turoctocog alfa in prophylaxis and treatment of bleeding episodes in severe haemophilia A: Final results from the guardian 2 extension trial
Authors: Lentz Steven R. , Janic Dragana , Kavakli Kaan , Miljic Predrag , Oldenburg Johannes , C. Ozelo Margareth , Santagostino Elena , Suzuki Takashi , Zupancic Šalek Silva , Korsholm Lars , Matytsina Irina , Tiede Andreas
Published: November 2018

Introduction

Turoctocog alfa is a recombinant factor VIII (FVIII) molecule, approved for treatment and prophylaxis of bleeding in patients with haemophilia A. In the guardian 1 (adolescents/adults) and guardian 3 (children) phase 3 trials, turoctocog alfa demonstrated a favourable efficacy and safety profile. Guardian 1 or 3 completers could enrol in the guardian 2 extension. Final guardian 2 results are reported here.

Aim

Investigate long‐term safety and efficacy of turoctocog alfa administered for prophylaxis and treatment of bleeds.

Methods

In this phase 3b open‐label trial, previously treated males of all ages with severe haemophilia A received prophylaxis regimens of turoctocog alfa or on‐demand treatment of bleeds. The primary safety endpoint was frequency of FVIII inhibitor development. Efficacy endpoints included annualized bleeding rate (ABR) during prophylaxis, haemostatic response in treatment of bleeds and number of injections required to treat bleeds.

Results

Overall, 213 patients were dosed with turoctocog alfa; 207 patients received prophylaxis; 19 received on‐demand treatment. No FVIII inhibitors (≥0.6 BU) were reported. For all patients on prophylaxis, overall median ABR was 1.37 bleeds/y; success rate for treatment of bleeds was 90.2%; and 88.2% of bleeds were controlled with 1‐2 injections of turoctocog alfa. For the on‐demand regimen, overall median ABR was 30.44 bleeds/y; success rate for treatment of bleeds was 96.7%; and 94.9% of bleeds were controlled with 1‐2 injections of turoctocog alfa.

Conclusion

Extended use of turoctocog alfa is safe and effective for prevention and treatment of bleeding episodes in previously treated patients with haemophilia A across all ages.
Serosal invasion is a strong prognostic factor for hepatocellular carcinoma after hepatectomy
Authors: Sakamoto Katsunori , Ogawa Kohei , Tohyama Taiji , Ueno Yoshitomo , Tamura Kei , Inoue Hitoshi , Nakamura Taro , Watanabe Jota , Takai Akihiro , Takada Yasutsugu
Published: November 2018

Aim

The clinical impact of serosal invasion by hepatocellular carcinoma (HCC) remains unclear. This study aimed to clarify the significance of serosal invasion as a prognostic factor for patients who underwent hepatectomy for HCC.

Methods

This retrospective study investigated patients who underwent hepatectomy for HCC between October 2003 and September 2016 in Ehime University Hospital (Toon, Japan). A total of 161 cases were enrolled after excluding cases of concomitant distant metastasis, macroscopic tumor remnant, mixed HCC, and rehepatectomy. We classified these 161 patients into groups with serosal invasion detected (S[+]) and serosal invasion undetected (S[−]). We compared patient characteristics, perioperative data, pathological findings, and prognosis between S(+) and S(−) groups.

Results

Serosal invasion was observed in 19 of the 161 patients (12%). The 5‐year recurrence‐free survival rate was lower for S(+) (13.0%) than for S(−) (28.7%, P = 0.006). The 5‐year overall survival (OS) rate was lower for S(+) (24.7%) than for S(−) (63.9%, P < 0.001). Regarding OS, serosal invasion, preoperative α‐fetoprotein value, presence of invasion to hepatic veins, and liver cirrhosis were independent predictors in multivariate analyses. The 3‐year OS rate after recurrence was poorer in the S(+) group (22.9%) than in the S(−) group (49.7%, P = 0.001).

Conclusions

Serosal invasion was a strong predictor of worse outcomes after hepatectomy for HCC. Patients showing serosal invasion need close postoperative follow‐up or consideration of adjuvant treatment.
Risk of neurosyphilis in HIV‐infected persons with syphilis lacking signs or symptoms of central nervous system infection
Authors: Rotman L , Luo X , Thompson A , Mackesy‐Amiti ME , Young LR , Young JD
Published: November 2018

Objectives

People living with HIV (PLWH) are at increased risk of asymptomatic neurosyphilis; thus, it has been common practice to perform a lumbar puncture (LP) in all PLWH presenting with syphilis regardless of stage, signs or symptoms. However, this practice varies widely among clinicians. Our objective was to elucidate the number of LPs required to diagnose a single case of asymptomatic neurosyphilis.

Methods

We performed an electronic health record (EHR) review of PLWH who were diagnosed with syphilis of any stage over a 10‐year period. EHRs were reviewed to determine the number of subjects who had an LP performed, what proportion had neurological signs or symptoms, and whether a diagnosis of neurosyphilis was made at presentation or follow‐up.

Results

In 261 separate episodes of syphilis in 230 subjects, we found the major risk factors for asymptomatic neurosyphilis to be low CD4 T‐cell count (P = 0.0007), high rapid plasma reagin (RPR) titre (P = 0.019) and lack of HIV virological suppression (P = 0.003). The majority of our subjects (78%) with neurosyphilis presented with central nervous system (CNS) symptoms. We estimate, if standard practice is to perform LP in all patients, that the number needed to test (NNTT) = 38.

Conclusions

This large number of potentially unnecessary LPs, along with heterogeneity of presentation, and the never‐nil risk of asymptomatic neurosyphilis should be incorporated into clinical decision‐making. The majority of PLWH presenting with a serological diagnosis of syphilis, but no neurological signs or symptoms, do not necessarily require an LP for an evaluation of asymptomatic neurosyphilis.
Composition effects on mechanical properties of pristine sodium borosilicate glass
Authors: Zhao Yan , Zhang Xiaoyang , Yuan Wei , Liu Fengfei , Sun Mengli , Peng Haibo , Wang Tieshan
Published: November 2018

Sodium borosilicate (NBS) glass is widely used in the disposal of high level nuclear waste nowadays. In order to understand the mechanism of hardness in NBS glass varies with various compositions, nanoindentation experiment and molecular dynamics simulation were carried out. Both experimental and calculated results suggested that, the hardness of glass increased with the ratio of R ([Na2O]/[B2O3] in molar percentage) and K ([SiO2]/[B2O3] in molar percentage). In the process of hardness increase, the [BO3] units were transformed into [BO4] units, which could lead to the polymerization increase for the glass system, and the transformation was linear to R. The hardness increase was also accompanying with the increase of silica content, which is another cause for polymerization increase. There are many possible factors that may affect the mechanical properties of pristine NBS glass, and polymerization increase should be the main reason for hardness increase, which could be resulted from the two processes above: (a) the transformation of [BO3] into [BO4]; (b) silica content increase.
Export versus FDI: Learning through propinquity
Authors: Creane Anthony , Miyagiwa Kaz
Published: November 2018

This paper considers the strategic role learning plays on the choice between FDI and export under demand and cost uncertainty. FDI allows a foreign firm to learn local demand, which is beneficial. However, as it buys inputs from the same local input markets as the rival home firm, two firms’ costs become perfectly correlated, which we prove harmful to the foreign firm. Thus, the interplay of the demand acquisition and the cost correlation effect affects FDI decisions. We show that FDI is more likely to occur when firms produce more differentiated goods and that FDI almost always reduces host country welfare.
Development of an 18‐item abbreviated Chinese version of Berger's HIV Stigma Scale
Authors: Yu Chia‐Hui , Huang Chu‐Yu , Lee Yuan‐Ti , Cheng Su‐Fen
Published: November 2018

Aim

Human immunodeficiency virus (HIV) stigma in people living with HIV is associated with depression and poor treatment adherence. The current literature lacks a Chinese instrument to measure HIV stigma in Taiwan. Thus, the purpose of this study was to develop an abbreviated Chinese translation version of Berger's HIV Stigma Scale.

Methods

The instrument development process was guided by Brislin's Translation Model of establishment of construct validity and convergent validity and verification of reliability.

Results

This study recruited 540 HIV‐infected adults (January‐November 2015). Data analysis using confirmatory factor analysis resulted in an 18‐item abbreviated Chinese version of Berger's HIV Stigma Scale, consisting with four factors: personalized stigma (seven items), disclosure concerns (three items), negative self‐image (four items), and concerns with public attitudes toward people with HIV (four items). The final model demonstrated a good fit. A positive correlation between HIV stigma and depression was found. The Cronbach α for internal consistency was 0.92.

Conclusion

The 18‐item abbreviated Chinese version of Berger's HIV Stigma Scale demonstrated adequate reliability and validity to assess HIV stigma among Chinese people living with HIV. It is a feasible tool that allows for rapid assessment of HIV‐related stigma.
HLA‐DR Class II expression on myeloid and lymphoid cells in relation to HLA‐DRB1 as a genetic risk factor for visceral leishmaniasis
Authors: Singh Bhawana , Fakiola Michaela , Sudarshan Medhavi , Oommen Joyce , Singh Siddharth Sankar , Sundar Shyam , Blackwell Jenefer M.
Published: November 2018

Genetic variation at HLA‐DRB1 is a risk factor for visceral leishmaniasis (VL) caused by Leishmania donovani. The single nucleotide polymorphism rs9271252 upstream of the DRB1 gene provides a perfect tag for protective versus risk HLA‐DRB1 four‐digit alleles. In addition to the traditional role of the membrane‐distal region of HLA class II molecules in antigen presentation and CD4 T‐cell activation, the membrane‐proximal region mediates ‘non‐traditional’ multi‐functional activation, differentiation, or death signals, including in DR‐expressing T cells. To understand how HLA‐DR contributes to disease pathogenesis, we examined expression at the protein level in circulating myeloid (CD14+, CD16+) and lymphoid (CD4+, CD8+, CD19+) cells of VL patients (pre‐ and post‐treatment) compared with endemic healthy controls (EHC). Although DR expression is reduced in circulating myeloid cells in active disease relative to EHC and post‐treatment groups, expression is enhanced on CD4+ DR+ and CD8+ DR+ T cells consistent with T‐cell activation. Cells of all myeloid and lymphoid populations from active cases were refractory to stimulation of DR expression with interferon‐γ (IFN‐γ). In contrast, all populations except CD19+ B cells from healthy blood bank controls showed enhanced DR expression following IFN‐γ stimulation. The rs9271252 genotype did not impact significantly on IFN‐γ‐activated DR expression in myeloid, B or CD8+ T cells, but CD4+ T cells from healthy individuals homozygous for the risk allele were particularly refractory to activated DR expression. Further analysis of DR expression on subsets of CD4+ T cells regulating VL disease could uncover additional ways in which pleiotropy at HLA DRB1 contributes to disease pathogenesis.
Mapping the Path Forward for Sustainable Supply Chain Management: A Review of Reviews
Authors: Carter Craig R. , Washispack Seth
Published: November 2018

This paper provides a systematic literature review (SLR) of 59 sustainable supply chain management (SSCM) SLRs. The key findings are that (1) we have reached a point of saturation, where we likely do not need additional SSCM SLRs that simply provide a broad overview of the content, themes, and structure of the SSCM literature (although periodic updates of existing SLRs may be warranted); however, (2) there is “white space” and opportunity to examine relationships among specific constructs and use SLRs for theory development; and (3) there is a need to improve the methodological rigor of future SSCM SLRs, as found through our introduction of a modified set of AMSTAR criteria to assess SLR quality. Finally, there is an opportunity for studies that move beyond metrics and investigation of performance from the perspective of a single organization to the broader supply chain.
Improvement of Japanese adults' English speaking skills via experiences speaking to a robot
Authors: Iio Takamasa , Maeda Ryota , Ogawa Kohei , Yoshikawa Yuichiro , Ishiguro Hiroshi , Suzuki Kaori , Aoki Tomohiro , Maesaki Miharu , Hama Mika
Published: November 2018

This paper reports how robot‐assisted language learning (RALL) impacts Japanese adults' English speaking skills. With existing research on RALL focusing on children, there is little evidence indicating RALL's effects on adults. We developed a RALL system comprising a robot, a tablet, and designed learning materials for speaking practice. To explore the effects of this system on the speaking skills of adults, we conducted a pretest and posttest designed pilot experiment. The participants in this study were nine female Japanese university students. The participants used the system for speaking practice for a total of 30 min per day for 7 days. The results of comparing the pretests with the posttests demonstrated that the adults' English speaking skills were enhanced; in particular, their speaking accuracy, fluency, and pronunciation improved greatly. This study contributes to providing clear evidence of the effects of RALL on Japanese adults' English speaking skills.
Monitoring serum proangiogenic cytokines from hepatocellular carcinoma patients treated with sorafenib
Authors: Adachi Takuya , Nouso Kazuhiro , Miyahara Koji , Oyama Atsushi , Wada Nozomu , Dohi Chihiro , Takeuchi Yasuto , Yasunaka Tetsuya , Onishi Hideki , Ikeda Fusao , Nakamura Shinichiro , Shiraha Hidenori , Takaki Akinobu , Takabatake Hiroyuki , Fujioka Shin‐ichi , Kobashi Haruhiko , Takuma Yoshitaka , Iwadou Shouta , Uematsu Shuji , Takaguchi Koichi , Hagihara Hiroaki , Okada Hiroyuki ,   on behalf of the Okayama Liver Cancer Group
Published: November 2018

Background and Aim

Several factors, including proangiogenic cytokines, have been reported as predictive markers for the treatment effect of sorafenib in patients with hepatocellular carcinoma (HCC); however, most of them were determined based on one‐time measurements before treatment.

Methods

We consecutively recruited 80 advanced HCC patients who were treated with sorafenib prospectively. Serum levels of eight proangiogenic cytokines and the appearance of adverse events were monitored periodically, and their correlations with the prognoses of the patients were evaluated.

Results

Among six significant risk factors for overall survival in univariate analyses, high angiopoietin‐2 (hazard ratio, 2.06), high hepatocyte growth factor (hazard ratio, 2.08), and poor performance status before the treatment (hazard ratio, 2.48) were determined as independent risk factors. In addition, high angiopoietin‐2 at the time of progressive disease was a marker of short post‐progression survival (hazard ratio, 4.27). However, there was no significant variable that predicted short progression‐free survival except the presence of hepatitis B virus surface antigen.

Conclusions

Predictions of overall survival and post‐progression survival were possible by periodically measuring serum proangiogenic cytokines, especially angiopoietin‐2, in patients with HCC treated with sorafenib.
Beneficial effect of butyrate‐producing Lachnospiraceae on stress‐induced visceral hypersensitivity in rats
Authors: Zhang Jindong , Song Lijin , Wang Yujing , Liu Chang , Zhang Lu , Zhu Shiwei , Liu Shuangjiang , Duan Liping
Published: November 2018

Background and Aim

Emerging evidence indicates that psychological stress is involved in the pathogenesis of irritable bowel syndrome, which is characterized by visceral hypersensitivity and may be accompanied by gut dysbiosis. However, how such stress contributes to the development of visceral hypersensitivity is incompletely understood. Here, we aimed to investigate the influence that stress‐induced microbial changes exert on visceral sensitivity, as well as the possible underlying mechanisms associated with this effect.

Methods

Male Sprague–Dawley rats underwent chronic water avoidance stress (WAS) to induce visceral hypersensitivity. Visceral sensitivity, colonic tight junction protein expression, and short‐chain fatty acids of cecal contents were measured. Fecal samples were collected to characterize microbiota profiles. In a separate study, oral gavage of Roseburia in WAS rats was conducted to verify its potential role in the effectiveness on visceral hypersensitivity.

Results

Repeated WAS caused visceral hypersensitivity, altered fecal microbiota composition and function, and decreased occludin expression in the colon. Stressed rats exhibited reduced representation of pathways involved in the metabolism of butyrate and reduced abundance of several operational taxonomic units associated with butyrate‐producing bacteria, such as Lachnospiraceae. Consistently, supplementation with Roseburia hominis, a species belonging to Lachnospiraceae, significantly increased cecal butyrate content. Moreover, Roseburia supplementation alleviated visceral hypersensitivity and prevented the decreased expression of occludin.

Conclusions

Reduction in the abundance of butyrate‐producing Lachnospiraceae, which is beneficial for the intestinal barrier, was involved in the formation of visceral hypersensitivity. R. hominis is a potential probiotic for treating stress‐induced visceral hypersensitivity.
Effects of in‐hospital exercise on sarcopenia in hepatoma patients who underwent transcatheter arterial chemoembolization
Authors: Koya Shunji , Kawaguchi Takumi , Hashida Ryuki , Hirota Keisuke , Bekki Masafumi , Goto Emiko , Yamada Maiko , Sugimoto Masako , Hayashi Saki , Goshima Norihiro , Yoshiyama Teruhito , Otsuka Takashi , Nozoe Ryosuke , Nagamatsu Ayu , Nakano Dan , Shirono Tomotake , Shimose Shigeo , Iwamoto Hideki , Niizeki Takashi , Matsuse Hiroo , Koga Hironori , Miura Hiroko , Shiba Naoto , Torimura Takuji
Published: November 2018

Background and Aim

Sarcopenia is a prognostic factor in hepatocellular carcinoma (HCC) patients. HCC patients who underwent transcatheter arterial chemoembolization (TACE) are at a risk of muscle atrophy. We aimed to investigate the effects of in‐hospital exercise on muscle mass and factors associated with muscle hypertrophy in HCC patients who underwent TACE.

Methods

We enrolled 209 HCC patients who underwent TACE. Patients were classified into either an exercise (n = 102) or control (n = 107) group. In the exercise group, patients were treated with in‐hospital exercise (median 2.5 metabolic equivalents/20–40 min/day). The effects of exercise on muscle mass were evaluated by changes in skeletal muscle index (ΔSMI) between before and after TACE. Factors associated with an increase in SMI were analyzed by logistic regression and decision‐tree analyses.

Results

There was no significant difference in serum albumin and bilirubin levels between the two groups. ΔSMI was significantly higher in the exercise group than in the control group (0.28 cm2/m2 vs −1.11 cm2/m2, P = 0.0029). In the logistic regression analysis, exercise was an independent factor for an increase in SMI (hazard ratio 2.13; 95% confidence interval 1.215–3.846; P = 0.0085). Moreover, the decision‐tree analysis showed that exercise was the initial divergence variable for an increase in SMI (the ratio of increased SMI: 53% in the exercise group vs 36% in the control group).

Conclusions

In‐hospital exercises increased muscle mass in HCC patients who underwent TACE. In addition, exercise was an independent factor for muscle hypertrophy. Thus, in‐hospital exercise may prevent sarcopenia in HCC patients who underwent TACE.
Inhibition, shifting and updating in relation to psychometric intelligence across ability groups in the psychiatric population
Authors: Biesmans K. E. , van Aken L. , Frunt E. M. J. , Wingbermühle P. A. M. , Egger J. I. M.
Published: November 2018

Background

Assessment of intelligence and executive function (EF) is common in complex neuropsychiatric practice. Although previous studies have shown that EF and intelligence are related, it is unknown whether these constructs relate to one another in a similar manner across different ability groups (mild intellectual disability, borderline intellectual disability and normal/high intelligence). This study therefore examines the relation between three EFs (inhibition, shifting and updating) and intelligence in a heterogeneous psychiatric sample. It is hypothesised that the strength of the relation between intelligence and the three EFs decreases when the level of intelligence increases, in accordance with Spearman's Law of Diminishing Returns.

Methods

In a cross‐sectional, between and within subject design, one of the three intelligence tests (Kaufman Adolescent and Adult Intelligence Test and Wechsler Adult Intelligence Scale – third and fourth editions) and several EF tests (Stroop Colour–Word Test, Trail Making Test and Spatial Working Memory task) were administered to 250 neuropsychiatric inpatients and outpatients (Mage = 39.8, standard deviation = 14.3, 52.8% male). Based upon their full‐scale IQ score, patients were divided into three ability groups (mild intellectual disability, borderline intellectual disability or normal/high intelligence). The relation between EF and intelligence was assessed through analyses of the correlation pattern; groups were compared using analysis of covariance.

Results

Analyses showed significant correlations between the constructs of EF and intelligence. A significant interaction effect was found for shifting, with highest correlations in the normal to high intelligence group, but not for inhibition and updating.

Conclusions

Results support a specific role for shifting in this EF–intelligence relation. The correlational pattern of updating and intelligence, as well as the differential relation of shifting and intelligence across ability groups, suggests that EF tasks may not measure distinct EFs in lower intellectual ability but rely on cognitive primitives such as processing speed. EF tasks can be considered less valid indicators of EF ability. Implications in terms of the need for development of specific tasks to measure cognition in low intellectual ability are discussed.
Lock‐In Effects in Relationship Lending: Evidence from DIP Loans
Authors: HASAN IFTEKHAR , RAMÍREZ GABRIEL G. , ZHANG GAIYAN
Published: November 2018

Do prior lending relationships result in pass‐through savings (lower interest rates) for borrowers, or do they lock in higher costs for borrowers? Theoretical models suggest that when borrowers experience greater information asymmetry, higher switching costs, and limited access to capital markets, they become locked into higher costs from their existing lenders. Firms in Chapter 11 seeking debtor‐in‐possession (DIP) financing often fit this profile. We investigate the presence of lock‐in effects using a sample of 348 DIP loans. We account for endogeneity using the instrument variable (IV) approach and the Heckman selection model and find consistent evidence that prior lending relationship is associated with higher interest costs and the effect is more severe for stronger existing relationships. Our study provides direct evidence that prior lending relationships do create a lock‐in effect under certain circumstances, such as DIP financing.
Upper molar morphology, homologies and evolutionary patterns of chinchilloid rodents (Mammalia, Caviomorpha)
Authors: Rasia Luciano Luis , Candela Adriana M.
Published: November 2018

Chinchilloidea are a clade of caviomorph rodents that includes seven living species, the Dinomyidae Dinomys branickii, the Chinchillidae Lagostomus maximus, two species of Chinchilla and three species of Lagidium. In addition, two extinct families are traditionally considered chinchilloids – Neoepiblemidae and Cephalomyidae. The phylogeny of the Chinchilloidea has so far not been well established and is based on partial analyses. Studying the anatomy and ontogeny of extinct and extant taxa, we propose homologies for the upper molars of Chinchilloidea for which these homologies have not been previously proposed: that is the Chinchillidae Prolagostomus, Lagostomus, Lagidium and Chinchilla, and the Neoepiblemidae Neoepiblema and Phoberomys. We identify patterns of occlusal simplification within Chinchilloidea and evaluate its importance in an evolutionary context. A phylogenetic analysis recovered Dinomyidae, Chinchillidae and Neoepiblemidae as clades. ‘Cephalomyidae’ have not been not recovered as a monophyletic group and ‘cephalomyids’ are closely related to Neoepiblemidae. Branisamys is not included within the Dinomyidae and appears to be a basal chinchilloid.
Value‐based assessment of hysterectomy approaches
Authors: Danilyants Natalya , MacKoul Paul , Baxi Rupen , van der Does Louise Q. , Haworth Leah R.
Published: November 2018

Aim

By evaluating operative outcomes relative to cost, we compared the value of minimally invasive hysterectomy approaches, including a technique discussed less often in the literature, laparoscopic retroperitoneal hysterectomy (LRH), which incorporates retroperitoneal dissection and ligation of the uterine arteries at their vascular origin.

Methods

Retrospective chart review of all women (N = 2689) aged greater than or equal to 18 years who underwent hysterectomy for benign conditions from 2011 to 2013 at a high‐volume hospital in Maryland, USA. Procedures included: laparoscopic supracervical hysterectomy, robotic‐assisted laparoscopic hysterectomy (RALH), total laparoscopic hysterectomy, laparoscopic‐assisted vaginal hysterectomy, total vaginal hysterectomy (TVH), and LRH.

Results

Total vaginal hysterectomy had the highest intraoperative complication rate (9.6%;P < 0.0001) but the lowest postoperative complication rate (1.8%;P < 0.0001). Robotics had the highest postoperative complication rate (11.4%;P < 0.0001). LRH had the shortest operative time (71.2 min;P < 0.0001) and the lowest intraoperative complication rates (2.1%;P < 0.0001). LRH and TVH were the least costly (averaging $4061 and $6416, respectively), while RALH was the most costly ($9354). Taking both operative outcomes and cost into account, LRH, TVH and laparoscopic‐assisted vaginal hysterectomy yielded the highest value scores; total laparoscopic hysterectomy, RALH, and laparoscopic supracervical hysterectomy yielded the lowest.

Conclusion

Understanding the value of surgical interventions requires an evaluation of both operative outcomes and direct hospital costs. Using a quality‐cost framework, the LRH approach as performed by high‐volume laparoscopic specialists emerged as having the highest calculated value.
Preventing anabolic steroid abuse: A long way to go
Authors: de Ronde W.
Published: November 2018

Click here to view the Original article by Dr. H. Horwitz et al.
Supplementation of L‐glycine and L‐glutamate to Japanese quails from 01 to 36 days of age using the ideal protein concept
Authors: Vieira Danilo V. G. , Silva José H. V. , Costa Fernando G. P. , Melo Thiago S. , Lima Matheus R. , Cavalcante Danilo T. , de Vargas Júnior José G. , Bonaparte Talita P. , Oliveira Lorena C.
Published: November 2018

Experiment I: T1‐1 = basal diet with 25% crude protein (CP) + limiting amino acids (LA); T1‐2 = 20% CP + LA; T1‐3 = 20% CP + LA + L‐glycine; T1‐4 = 20% CP + LA + L‐glutamate; T1‐5 = 20% CP + LA + L‐glycine + L‐glutamate. Experiment II: T2‐1 = basal diet with 22% CP + LA; T2‐2 = 20% CP + LA; T2‐3 = 17.6% CP + LA + L‐glycine; T2‐4 = 17.6% CP + LA + L‐glutamate; T2‐5 = 17.6% CP + LA + L‐glycine + L‐glutamate. The reduction of dietary protein based on the concept of ideal protein decreases nitrogen excretion in quails when L‐glycine is added to the diets. Quails fed diets supplemented with L‐glutamate as the non‐specific nitrogen source equivalent to the nitrogen level of the control diet had increased nitrogen excretion. However, quails had reduced nitrogen excretion in both experiments when L‐glycine was added to diets with L‐glutamate. Carcass fat was increased by reducing dietary protein, but fat deposition was reduced by adding L‐glutamate and L‐glycine, or both. The dietary addition of L‐glutamate and L‐glycine in quails based on the ideal protein concept is not necessary (Exp. I). Although the total nitrogen, electrolytic balance and glycine level were adjusted in diets, quails had decreased performance. Therefore, other hypotheses besides protein reduction need to be studied (Exp. II). Protein reduction with supplementation of only limiting essential amino acids does not affect quail performance. Dietary addition of L‐glycine reduces nitrogen excretion.
Characterisation of the Toxoplasma gondii tyrosine transporter and its phosphorylation by the calcium‐dependent protein kinase 3
Authors: Wallbank Bethan A. , Dominicus Caia S. , Broncel Malgorzata , Legrave Nathalie , Kelly Gavin , MacRae James I. , Staines Henry M. , Treeck Moritz
Published: November 2018

Toxoplasma gondii parasites rapidly exit their host cell when exposed to calcium ionophores. Calcium‐dependent protein kinase 3 (TgCDPK3) was previously identified as a key mediator in this process, as TgCDPK3 knockout (∆cdpk3) parasites fail to egress in a timely manner. Phosphoproteomic analysis comparing WT with ∆cdpk3 parasites revealed changes in the TgCDPK3‐dependent phosphoproteome that included proteins important for regulating motility, but also metabolic enzymes, indicating that TgCDPK3 controls processes beyond egress. Here we have investigated a predicted direct target of TgCDPK3, ApiAT5‐3, a putative transporter of the major facilitator superfamily, and show that it is rapidly phosphorylated at serine 56 after induction of calcium signalling. Conditional knockout of apiAT5‐3 results in transcriptional upregulation of most ribosomal subunits, but no alternative transporters, and subsequent parasite death. Mutating the S56 to a non‐phosphorylatable alanine leads to a fitness cost, suggesting that phosphorylation of this residue is beneficial, albeit not essential, for tyrosine import. Using a combination of metabolomics and heterologous expression, we confirmed a primary role in tyrosine import for ApiAT5‐3. However, no significant differences in tyrosine import could be detected in phosphorylation site mutants showing that if tyrosine transport is affected by S56 phosphorylation, its regulatory role is subtle.
Nuclear abnormalities in vascular myocytes in cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
Authors: Dziewulska Dorota , Nycz Ewelina , Rajczewska‐Oleszkiewicz Cecylia , Bojakowski Jacek , Sulejczak Dorota
Published: November 2018

Cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a stroke and dementia syndrome with degeneration and loss of vascular smooth muscle cells (VSMCs). The disease is due to mutations in NOTCH3 playing an important role in VSMC differentiation, proliferation and apoptosis. Searching for a possible cause of VSMC dysfunction in CADASIL, we investigated morphology and proliferative activity the affected myocytes. In material from autopsy brains and skin‐muscle biopsies of patients with CADASIL diagnosis, assessment of VSMCs in arterial vessels at the level of light and electron microscopy was performed. Proliferative activity of VSMCs was evaluated in immune reactions to proliferative markers: proliferating cell nuclear antigen, and cyclins B1 and D. In CADASIL, abnormal morphology of VSMC nuclei was observed in 18.1%, 11.5%, and 6.9% of the cerebral, skin, and skeletal muscle vessels, respectively. The affected myocytes showed variability in nuclear size, irregularity in nuclear shape, and abnormal chromatin appearance. Frequently, double nuclei of equal size or micronuclei were observed. Sometimes, even multinuclear myocytes were found. In some of the nuclei immune reactions to the examined proliferative markers were positive. Aberrant structure and number of VSCM nuclei, and their immunoreactivity to proliferative markers suggest mitotic instability of vascular myocytes in CADASIL. We speculate that mutant NOTCH3 which is unable to control properly VSMC proliferation, and may be responsible for their premature or inappropriate entry into mitosis, irreversible arrest of the cell cycle, senescence or degeneration and loss.
The auxin influx carrier, OsAUX3, regulates rice root development and responses to aluminium stress
Authors: Wang Mei , Qiao JiYue , Yu ChenLiang , Chen Hao , Sun ChenDong , Huang LinZhou , Li ChuanYou , Geisler Markus , Qian Qian , Jiang De An , Qi YanHua
Published: November 2018

In rice, there are five members of the auxin carrier AUXIN1/LIKE AUX1 family; however, the biological functions of the other four members besides OsAUX1 remain unknown. Here, by using CRISPR/Cas9, we constructed two independent OsAUX3 knock‐down lines, osaux3‐1 and osaux3‐2, in wild‐type rice, Hwayoung (WT/HY) and Dongjin (WT/DJ). osaux3‐1 and osaux3‐2 have shorter primary roots (PRs), decreased lateral root (LR) density, and longer root hairs (RHs) compared with their WT. OsAUX3 expression in PRs, LRs, and RHs further supports that OsAUX3 plays a critical role in the regulation of root development. OsAUX3 locates at the plasma membrane and functions as an auxin influx carrier affecting acropetal auxin transport. OsAUX3 is up‐regulated in the root apex under aluminium (Al) stress, and osaux3‐2 is insensitive to Al treatments. Furthermore, 1‐naphthylacetic acid accented the sensitivity of WT/DJ and osaux3‐2 to respond to Al stress. Auxin concentrations, Al contents, and Al‐induced reactive oxygen species‐mediated damage in osaux3‐2 under Al stress are lower than in WT, indicating that OsAUX3 is involved in Al‐induced inhibition of root growth. This study uncovers a novel pathway alleviating Al‐induced oxidative damage by inhibition of acropetal auxin transport and provides a new option for engineering Al‐tolerant rice species.