bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Reduces Arterial Remodeling by Inhibiting Sonic Hedgehog‐Stimulated Stem Cell Antigen‐1 Positive Progenitor Stem Cell Expansion
Authors: Fitzpatrick Emma , Han Xu , Liu Weimin , Corcoran Eoin , Burtenshaw Denise , Morrow David , Helt Jay‐Christian , Cahill Paul A. , Redmond Eileen M.
Published: September 2017

Background

Cell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate ethanol (EtOH) on sonic hedgehog (SHh) signaling in regulating possible stem cell antigen‐1 positive (Sca1+) progenitor stem cell involvement during pathologic arterial remodeling.

Methods

Partial ligation or sham operation of the left carotid artery was performed in transgenic Sca1‐enhanced green fluorescent protein (eGFP) mice gavaged with or without “daily moderate” EtOH.

Results

The EtOH group had reduced adventitial thickening and less neointimal formation, compared to ligated controls. There was expansion of eGFP‐expressing (i.e., Sca1+) cells in remodeled vessels postligation (day 14), especially in the neo intima. EtOH treatment reduced the number of Sca1+ cells in ligated vessel cross‐sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 and Gli2, and RT–PCR of whole‐vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1‐eGFP mice with the SHh signaling inhibitor cyclopamine diminished SHh target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh‐induced differentiation to vascular smooth muscle cells.

Conclusions

EtOH reduces SHh‐responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.
Influence of Cocaine‐Related Images and Alcohol Administration on Inhibitory Control in Cocaine Users
Authors: Pike Erika , Marks Katherine R. , Stoops William W. , Rush Craig R.
Published: September 2017

Background

Alcohol use and impulsivity, including decreased inhibitory control, predict poor treatment outcomes for individuals with cocaine use disorders. This study sought to determine the effects of alcohol administration on inhibitory control following cocaine‐related and neutral cues on the Attentional Bias‐Behavioral Activation (ABBA) task in cocaine users. We hypothesized that the proportion of inhibitory failures would increase following cocaine, compared to neutral, cues. We further hypothesized that there would be an interaction between alcohol administration and task version, such that alcohol would impair inhibitory control following cocaine, but not neutral cues.

Methods

Fifty current cocaine users completed this mixed‐model, double‐blind, placebo‐controlled, crossover study over 2 experimental sessions. The ABBA task was completed following alcohol administration (0.0 and 0.65 g/kg). Subject‐rated drug effect and physiological measures were collected prior to and after alcohol administration.

Results

Proportion of inhibitory failures was increased following cocaine‐related cues compared to neutral cues independent of alcohol dose. Alcohol administration also produced prototypical subject‐rated drug effects.

Conclusions

A better understanding of the relationship between alcohol consumption and inhibitory control in cocaine users could direct the development of interventions to decrease the risk of relapse in individuals who drink and display impaired inhibitory control.
Comparison of the percentages of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia
Authors: El‐Chennawi Farha , Rageh Ibrahim Mohamed , Mansour Amira Ibrahim , Darwish Mohammed Ibrahim , Elghzaly Ashraf Antar , Sakr Basma El Sayed , Elbaz Khaled Mohsen
Published: September 2017

Problem

Little is known about how preeclampsia affects regulatory T‐cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.

Method of study

The percentage of umbilical cord blood CD4+ CD25high FOXP3+, CD4+ CD25low FOXP3+, and CD4+ FOXP3+ Tregs were analyzed by flow cytometry.

Results

CD4+ CD25high FOXP3+ Treg (%) and CD4+ FOXP3+ Treg (%) were significantly lower, while CD4+ CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers.

Conclusion

Preeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+ CD25high FOXP3+) in the umbilical cord blood of babies born to preeclamptic mothers.
Undifferentiated connective tissue diseases and adverse pregnancy outcomes. An undervalued association?
Authors: Spinillo Arsenio , Beneventi Fausta , Caporali Roberto , Ramoni Veronique , Montecucco Carlomaurizio
Published: September 2017

Undifferentiated connective tissue diseases (UCTDs) are a heterogeneous group of disorders characterized by symptoms and signs suggestive of systemic autoimmune rheumatic disease (ARD), but which do not fulfill all the established criteria for definite diagnosis of a condition. Although a third of UCTDs can progress to a definite ARD within months or years, most UCTDs can remain stable for years with minimal disease activity. The annual incidence of UCTD in the general population ranges from 14 to 140 per 100 000 people. UCTDs are associated with the persistence of several circulating autoantibodies including antinuclear, antiphospholipid or antithyroid antibodies. Immunological evaluation of subjects with UCTDs suggests a proinflammatory state and dysregulation of the Th1/Th2 balance. Autoantibodies have well‐known deleterious effects on placentation and have been associated with an increased risk of prematurity, fetal growth restriction (FGR), preeclampsia, and congenital atrioventricular heart block. Although epidemiological and biological data suggest a potential negative impact on reproductive outcomes, the relationship between UCTD and pregnancy outcomes has not been adequately studied. While awaiting definitive data from large studies, obstetricians should be aware that rheumatic disorders in their early, incomplete, or undifferentiated phases can adversely affect pregnancy outcomes, increasing the likelihood of pregnancy loss, FGR, preeclampsia, and prematurity.
Safety and efficacy of intravenous iron polymaltose, iron sucrose and ferric carboxymaltose in pregnancy: A systematic review
Authors: Qassim Alaa , Mol Ben W. , Grivell Rosalie M. , Grzeskowiak Luke E.
Published: September 2017

Background

Intravenous (IV) iron in pregnancy is useful where oral iron is not tolerated or a rapid replenishment of iron is required.

Aims

To review the literature on the efficacy and safety of different IV iron preparations in the management of antenatal iron‐deficiency anaemia (IDA).

Materials and methods

We searched MEDLINE, Embase and Scopus from inception to June 2016. Eligible studies were randomised controlled trials (RCTs) and observational studies, involving administration of IV iron (ferric carboxymaltose (FCM), iron polymaltose (IPM) or iron sucrose (IS)), regardless of comparator, to manage antenatal IDA. Two independent reviewers selected studies, extracted data and assessed quality.

Results

A total of 47 studies were eligible (21 RCTs and 26 observational studies), investigating IS (n = 2635; 41 studies), FCM (n = 276; four studies) and IPM (n = 164; three studies). All IV preparations resulted in significant improvements in haematological parameters, with a median increase of 21.8 g/L at 3–4 weeks and 30.1 g/L by delivery, but there was no evidence of any associated improvements in clinical outcomes. A greater median increase in Hb was observed with a high (25 g/L; range: 20–39.6 g/L) compared with low dose (20 g/L; range: 6.2–50.3 g/L). The median prevalence of adverse drug reactions for IPM (2.2%; range: 0–4.5%) was lower than FCM (5.0%; range: 0–20%) and IS (6.7%; range: 0–19.5%).

Conclusion

While IV iron in pregnancy improves haematological parameters, there is an absence of evidence for improvements in important maternal or perinatal outcomes. No single preparation of IV iron appeared to be superior, with the current IV iron preparation of choice largely determined by cost and convenience around administration.
Why are negative behaviours likely to be immediately invoked traits? The effects of valence and frequency on spontaneous trait inferences
Authors: Shimizu Yuki
Published: September 2017

People make trait inferences immediately when observing others’ behaviours. Previous studies reported that this spontaneous trait inference (STI) occurs more strongly from negative behaviours than from positive behaviours. However, what is responsible for this negativity bias in STI is unclear. In this study, two experiments investigated the effects of valence (an event's affective positivity or negativity) and frequency (how frequently the behaviour is observed in everyday life) on the occurrence of STI using an adapted version of a savings‐in‐relearning paradigm. Experiment 1 revealed that only valence affected the frequent occurrence of STI. In addition, the instructions to suppress impression formation or to focus attention on an actor's face made no difference to the results. In Experiment 2, the negativity bias in STIs was shown a week after exposure to the behavioural stimuli. These results suggest that the negativity bias in STIs occurs robustly, and the negative valence of observed behaviour is mostly responsible for the negativity bias in STI. The importance of immediate categorization of negative stimuli is discussed in terms of ecological priority.
Myocardial bridging is associated with exercise‐induced ventricular arrhythmia and increases in QT dispersion
Authors: Nishikii‐Tachibana Makiko , Pargaonkar Vedant S. , Schnittger Ingela , Haddad Francois , Rogers Ian S. , Tremmel Jennifer A. , Wang Paul J.
Published: September 2017

Background

A myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort.

Methods

We studied the rest and stress ECG tracings of patients with an MB suspected by focal septal buckling on exercise echocardiography (EE) (Echo‐MB group, N = 510), those with an MB confirmed by another examination (MB group, N = 110), and healthy controls (Control group, N = 198).

Results

The frequency of exercise‐induced premature ventricular contractions (PVCs) was significantly higher in the Echo‐MB and MB groups compared with the Control group (both p < .001). In all, 25 patients (4.9%) in the Echo‐MB group, seven patients (6.4%) in the MB group and no patients in the Control group had exercise‐induced non‐sustained ventricular tachycardia (NSVT). There was no difference in the baseline QTd between the groups. In the Echo‐MB and MB groups, QTd postexercise increased significantly when compared with baseline (both p < .001). Patients with NSVT had a higher frequency of male gender and an even greater increase in QTd with exercise compared with the non‐NSVT group.

Discussion

There is an increased frequency of exercise‐induced PVCs and NSVT in patients with MBs. Exercise significantly increases QTd in MB patients, with an even greater increase in QTd in MB patients with NSVT. Exercise in MB patients results in ventricular arrhythmias and abnormalities in repolarization.
Prostate cancer treatment in renal transplant recipients: a systematic review
Authors: Marra Giancarlo , Dalmasso Ettore , Agnello Marco , Munegato Stefania , Bosio Andrea , Sedigh Omidreza , Biancone Luigi , Gontero Paolo
Published: September 2017

The aim of this review was to summarize the current evidence and to highlight the main issues future research needs to address regarding prostate cancer (PCa) treatment in renal transpant recipients (RTRs). We conducted a search of AMED, Medline and Embase up to 17 November 2016 to investigate oncological and functional outcomes of PCa treatment in RTR. Type and use/protocols of immunosuppression and peri‐operative antibiotic drugs were also assessed. The search was implemented manually. Exclusion criteria were absence of full text or absence of information that allowed us to differentiate oncological and/or functional outcomes of each therapeutic approach used. We included 241 patients from 27 retrospective studies published between 1991 and 2016; seven of the studies were case–control and 20 were case series. We also considered nine case reports published between 1999 and 2016. Follow‐up ranged from 1 to 120 months. PCa was organ‐confined, with Gleason score ≤6 in 75.2% and 60.4% of patients. Surgery was the most frequent treatment used (n = 186), for which cancer‐specific (CSS) and overall survival (OS) rates were both 96.8%. Functional outcomes, including continence and erectile function, and complications were less frequently reported and were generally similar to those reported for radical prostatectomy (RP) in non‐RTRs. Other treatment methods in the patients included in the review were radiotherapy (RT) ± androgen deprivation therapy (ADT; n = 34; OS 88.2%; CSS 88.2%), ADT alone (n = 14; OS 42.9%; CSS 64.3%), brachytherapy (BT; n = 11; OS and CSS 100%), watchful waiting (n = 4) and active surveillance (n = 1). Overall no treatment‐related graft loss occurred. Immunosuppression and antibiotic schemes were poorly reported and inconsistent. Outcomes of PCa treatment in RTRs are encouraging and do not appear to be inferior to those of non‐RTR. RP was the most commonly assessed approach, whilst RT, BT and ADT were less frequent. Immunosuppression and antibiotic use were poorly reported and highly variable. High‐quality studies are needed because the current level of evidence is low, and our results should therefore be interpreted with caution.
Fetal microchimerism in human brain tumors
Authors: Broestl Lauren , Rubin Joshua B. , Dahiya Sonika
Published: September 2017

Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal‐in‐maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men. Quantitative PCR was used to detect the presence of male DNA in tumor samples from women with a positive history of male pregnancy and a diagnosis of either glioblastoma or meningioma. Fluorescence in situ hybridization for the X and Y chromosomes was used to verify the existence of intact male cells within tumor tissue. Fetal microchimerism was found in approximately 80% of glioblastoma cases and 50% of meningioma cases. No correlations were identified between the presence of microchimerism and commonly used clinical or molecular diagnostic features of disease. The impact of fetal microchimeric cells should be evaluated prospectively.
Reimagining GIScience for relational spaces
Authors: Bergmann Luke , O'Sullivan David
Published: September 2017

A mismatch between largely absolute Newtonian models of space in GIScience and the relational spaces of critical human geography has contributed to mutual disinterest between the fields. Critical GIS has offered an intellectual critique of GIScience without substantially altering how particular key geographical concepts are expressed in data structures. Although keystone ideas in GIScience such as Tobler's “First Law” and the modifiable areal unit problem speak to enduring concerns of human geography, they have drawn little interest from that field. Here, we suggest one way to reformulate the computational approach to the region for relational space, so that regions emerge not through proximity in an absolute space or similarities in intensive properties, but according to their similarities in relations. We show how this might operate theoretically and empirically, working through three illustrative examples. Our approach gestures toward reformulating key terms in GIScience like distance, proximity, networks, and spatial building blocks such as the polygon. Re‐engaging the challenges of representing geographical concepts computationally can yield new kinds of GIS and GIScience resonant with theoretical ideas in human geography, and also lead to critical human geographic practices less antagonistic to computation.
Cancer‐specific mortality of high‐risk prostate cancer after carbon‐ion radiotherapy plus long‐term androgen deprivation therapy
Authors: Kasuya Goro , Ishikawa Hitoshi , Tsuji Hiroshi , Haruyama Yasuo , Kobashi Gen , Ebner Daniel K. , Akakura Koichiro , Suzuki Hiroyoshi , Ichikawa Tomohiko , Shimazaki Jun , Makishima Hirokazu , Nomiya Takuma , Kamada Tadashi , Tsujii Hirohiko ,   the Working Group for Genitourinary Tumors
Published: September 2017

The treatment outcomes of patients with high‐risk localized prostate cancer (PC) after carbon‐ion radiotherapy (CIRT) combined with long‐term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC‐specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed‐dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high‐risk or very‐high‐risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow‐up time was 88.4 months, and the 5‐/10‐year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9–10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10‐year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10‐year follow‐up (10‐year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high‐risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high‐risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high‐risk PC patients treated with CIRT.
Genetic trade‐off: Resistance to malaria or susceptibility to multiple sclerosis
Authors: Ochi Hirofumi
Published: September 2017

Many types of genetic variations have evolved in humans as a result of evolutionary adaptation to malaria. Steri et al. reported that a genetic variant that provided resistance to Plasmodium falciparum or Plasmodium vivax malaria might have increased the susceptibility to multiple sclerosis among Sardinians.
Quarantine, isolation and the duty of easy rescue in public health
Authors: Giubilini Alberto , Douglas Thomas , Maslen Hannah , Savulescu Julian
Published: September 2017

We address the issue of whether, why and under what conditions, quarantine and isolation are morally justified, with a particular focus on measures implemented in the developing world. We argue that the benefits of quarantine and isolation justify some level of coercion or compulsion by the state, but that the state should be able to provide the strongest justification possible for implementing such measures. While a constrained form of consequentialism might provide a justification for such public health interventions, we argue that a stronger justification is provided by a principle of State Enforced Easy Rescue: a state may permissibly compel individuals to engage in activities that entail a small cost to them but a large benefit to others, because individuals have a moral duty of easy rescue to engage in those activities. The principle of State Enforced Easy Rescue gives rise to an Obligation Enforcement Requirement: the state should create the conditions such that submitting to coercive or compulsive measures becomes a fundamental moral duty of individuals, i.e. a duty of easy rescue. When the state can create such conditions, it has the strongest justification possible for implementing coercive or compulsive measures, because individuals have a moral duty to temporarily relinquish the rights that such measures would infringe. Our argument has significant implications for how public health emergencies in the developing world should be tackled. Where isolation and quarantine measures are necessary, states or the international community have a moral obligation to provide certain benefits to those quarantined or isolated.
Reconciling female genital circumcision with universal human rights
Authors: Gordon John‐Stewart
Published: September 2017

One of the most challenging issues in cross‐cultural bioethics concerns the long‐standing socio‐cultural practice of female genital circumcision (FGC), which is prevalent in many African countries and the Middle East as well as in some Asian and Western countries. It is commonly assumed that FGC, in all its versions, constitutes a gross violation of the universal human rights of health, physical integrity, and individual autonomy and hence should be abolished. This article, however, suggests a mediating approach according to which one form of FGC, the removal of the clitoris foreskin, can be made compatible with the high demands of universal human rights. The argument presupposes the idea that human rights are not absolutist by nature but can be framed in a meaningful, culturally sensitive way. It proposes important limiting conditions that must be met for the practice of FGC to be considered in accordance with the human rights agenda.
Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo‐controlled randomized study
Authors: Dagogo‐Jack Samuel , Liu Jie , Eldor Roy , Amorin Guillermo , Johnson Jeremy , Hille Darcy , Liao Yuqin , Huyck Susan , Golm Gregory , Terra Steven G. , Mancuso James P. , Engel Samuel S. , Lauring Brett
Published: September 2017

Aims

To assess ertugliflozin in patients with type 2 diabetes who are inadequately controlled by metformin and sitagliptin.

Materials and Methods

In this double‐blind randomized study (Clinicaltrials.gov NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53‐91 mmol/mol] receiving metformin ≥1500 mg/d and sitagliptin 100 mg/d; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2) were randomized to ertugliflozin 5 mg once‐daily, 15 mg once‐daily or placebo. The primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52.

Results

A total of 464 patients were randomized (mean baseline HbA1c, 8.0% [64.3 mmol/mol]; eGFR, 87.9 mL/min/1.73 m2). After 26 weeks, placebo‐adjusted least squares (LS) mean changes in HbA1c from baseline were −0.7% (−7.5 mmol/mol) and −0.8% (−8.3 mmol/mol) for ertugliflozin 5 and 15 mg, respectively (both P < .001); 17.0%, 32.1% and 39.9% of patients receiving placebo, ertugliflozin 5 mg or ertugliflozin 15 mg, respectively, had HbA1c <7.0% (53 mmol/mol). Significant reductions in fasting plasma glucose, body weight (BW) and systolic blood pressure (SBP) were observed with ertugliflozin relative to placebo. The positive effects of ertugliflozin on glycaemic control, BW and SBP were maintained through Week 52. A higher incidence of genital mycotic infections was observed in male and female patients receiving ertugliflozin (3.7%‐14.1%) vs placebo (0%‐1.9%) through Week 52. The incidence of urinary tract infections, symptomatic hypoglycaemia and hypovolaemia adverse events were not meaningfully different across groups.

Conclusions

Ertugliflozin added to metformin and sitagliptin was well‐tolerated, and provided clinically meaningful, durable glycaemic control, BW and SBP reductions vs placebo over 52 weeks.
Education for global citizenship and sustainable development in social science textbooks
Authors: Jimenez Jeremy David , Lerch Julia , Bromley Patricia
Published: September 2017

This article reviews the state of research and data on relevant content, broadly understood as sustainable development, in social science textbooks worldwide. Specifically, it examines the extent to which these textbooks could help learners to acquire the knowledge, skills and values that are needed to meet goal 4.7 of the United Nation's Sustainable Development Goals: ‘By 2030, ensure that all learners acquire the knowledge and skills needed to promote sustainable development, including, among others, through education for sustainable development and sustainable lifestyles, human rights, gender equality, promotion of a culture of peace and non‐violence, global citizenship and appreciation of cultural diversity and of culture's contribution to sustainable development’. It reviews relevant literature and analyses three cross‐national, longitudinal databases containing information that is coded from textbook content to assess the current state of knowledge. In addition to analysing measures concerning the environment and sustainable development, this article also focuses on areas of human rights, global citizenship, gender equality, and multiculturalism/social diversity. We find that textbook discussions of these variables have, in general, steadily increased since the middle of the 20th century. The article concludes by indicating where future research efforts are most needed, identifying geographic and substantive needs, and considering monitoring mechanisms that could encourage on‐going evaluation and monitoring of textbook content.
Partnering to change the world for people with haemophilia: 7th Haemophilia Global Summit, Madrid, Spain 22–24 September 2016
Authors: Dolan Gerry
Published: September 2017

The 7th Haemophilia Global Summit was held in Madrid, Spain, in September 2016. With a programme designed, for the 6th consecutive year, by a Scientific Steering Committee of haemophilia experts, the aim of the summit was to share optimal management strategies for haemophilia at all life stages and to provide an opportunity for specialists from across the haemophilia multidisciplinary care team to engage in discussion and debate with leading international experts on current and future areas of research. Topics covered ranged from the optimisation of haemophilia management, emerging issues in clinical care, practical approaches and future perspectives, in addition to patient engagement and empowerment in modern haemophilia care.
Does an observer's empathy influence my pain? Effect of perceived empathetic or unempathetic support on a pain test
Authors: Fauchon C. , Faillenot I. , Perrin A. M. , Borg C. , Pichot V. , Chouchou F. , Garcia‐Larrea L. , Peyron R.
Published: September 2017

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions. In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre‐recorded in study 1. Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings. These results suggest that empathetic feedback from observers has a positive influence on pain appraisal and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter‐individual variation. As in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input.
The neurobiological bases of autism spectrum disorders: the R451C‐neuroligin 3 mutation hampers the expression of long‐term synaptic depression in the dorsal striatum
Authors: Martella Giuseppina , Meringolo Maria , Trobiani Laura , De Jaco Antonella , Pisani Antonio , Bonsi Paola
Published: September 2017

Autism spectrum disorders (ASDs) comprise a heterogeneous group of disorders with a complex genetic etiology. Current theories on the pathogenesis of ASDs suggest that they might arise from an aberrant synaptic transmission affecting specific brain circuits and synapses. The striatum, which is part of the basal ganglia circuit, is one of the brain regions involved in ASDs. Mouse models of ASDs have provided evidence for an imbalance between excitatory and inhibitory neurotransmission. Here, we investigated the expression of long‐term synaptic plasticity at corticostriatal glutamatergic synapses in the dorsal striatum of the R451C‐NL3 phenotypic mouse model of autism. This mouse model carries the human R451C mutation in the neuroligin 3 (NL3) gene that has been associated with highly penetrant autism in a Swedish family. The R451C‐NL3 mouse has been shown to exhibit autistic‐like behaviors and alterations of synaptic transmission in different brain areas. However, excitatory glutamatergic transmission and its long‐term plasticity have not been investigated in the dorsal striatum so far. Our results indicate that the expression of long‐term synaptic depression (LTD) at corticostriatal glutamatergic synapses in the dorsal striatum is impaired by the R451C‐NL3 mutation. A partial rescue of LTD was obtained by exogenous activation of cannabinoid CB1 receptors or enhancement of the endocannabinoid tone, suggesting that an altered cannabinoid drive might underlie the deficit of synaptic plasticity in the dorsal striatum of R451C‐NL3 mice.
Effects of spatial smoothing on functional brain networks
Authors: Alakörkkö Tuomas , Saarimäki Heini , Glerean Enrico , Saramäki Jari , Korhonen Onerva
Published: September 2017

Graph‐theoretical methods have rapidly become a standard tool in studies of the structure and function of the human brain. Whereas the structural connectome can be fairly straightforwardly mapped onto a complex network, there are more degrees of freedom in constructing networks that represent functional connections between brain areas. For functional magnetic resonance imaging (fMRI) data, such networks are typically built by aggregating the blood‐oxygen‐level dependent signal time series of voxels into larger entities (such as Regions of Interest in some brain atlas) and determining their connection strengths from some measure of time‐series correlations. Although it is evident that the outcome must be affected by how the voxel‐level time series are treated at the preprocessing stage, there is a lack of systematic studies of the effects of preprocessing on network structure. Here, we focus on the effects of spatial smoothing, a standard preprocessing method for fMRI. We apply various levels of spatial smoothing to resting‐state fMRI data and measure the changes induced in functional networks. We show that the level of spatial smoothing clearly affects the degrees and other centrality measures of functional network nodes; these changes are non‐uniform, systematic, and depend on the geometry of the brain. The composition of the largest connected network component is also affected in a way that artificially increases the similarity of the networks of different subjects. Our conclusion is that wherever possible, spatial smoothing should be avoided when preprocessing fMRI data for network analysis.
Profiting from Innovation through Cross‐Border Market co‐Creation and co‐Opetition: The Case of Global Pharmaceuticals
Authors: Pitelis Christos N. , Desyllas Panos , Panagopoulos Andreas
Published: September 2017

We study the impact of the new intellectual property (IP) regime, as shaped by international agreements such as the Trade‐Related Aspects of Intellectual Property Rights (TRIPS), on the competitive positions of emerging country firms and advanced country multinational enterprises (AMNEs). Drawing on ideas from the IP, international business, and strategic management literatures, we formalize the market co‐creation perspective and extend it to the emerging country – AMNE context. Using the pharmaceutical industry as our focus, we show that market co‐creation‐based co‐opetition is preferable to both emerging and advanced country firms when the former can leverage their firm‐ and country‐specific advantages and complementary assets to co‐create new market space, even as they compete for value capture. We further show that co‐opetition is fostered when the bargaining power of the AMNE (afforded through trade agreements) is counterbalanced by actions of emerging country firms and a robust IP law interpretation and enforcement by the host country's courts.
The effectiveness of asset, liability and equity hedging against catastrophe risk: the cases of winter storms in North America and Europe
Authors: Wu Yang‐Che , Yang Ming Jing
Published: September 2017

The winter storms in North America and Europe are responsible for the majority of the insured natural catastrophe losses. This study analyzes the effectiveness of insurers hedging against the winter storm risk in terms of asset (catastrophe derivatives), liability (catastrophe bonds) and equity (catastrophe equity puts) risk management perspectives. The analysis results of the various financial performances show that our suggested hedging strategies are effective based on the long‐term positive profit and the improvement in the insolvency ratios. The conclusions of this study provide the insurers with less volatile premiums and more diversified portfolios under catastrophe risk management.
How numbers of the future are shaping today: The role of forecasts and calculations in public sector strategic thinking
Authors: Brorström Sara
Published: September 2017

This article examines the role of numbers in forming a city strategy in the case of Gothenburg, Sweden. The article illustrates how numbers make people act and react and shape the strategy process. The study is situated between the theoretical fields of accounting and strategy processes in cities. By relating them to the concept of ‘governmentality’, numbers are seen as helping render the city governable. Because strategizing is seen as concerning the future, the actors involved in drafting the strategy feel free to challenge historically institutionalized practices. The effect is paradoxical: the future‐looking strategy process becomes a forum for solving current problems.
Estimation of P‐S‐N curves in very‐high‐cycle fatigue: Statistical procedure based on a general crack growth rate model
Authors: Paolino D.S. , Tridello A. , Chiandussi G. , Rossetto M.
Published: September 2017

Extensive experimental investigations show that internal defects play a key role in the very‐high‐cycle fatigue (VHCF) response of metallic materials and that crack growth from internal defects can take place even if the stress intensity factor associated to the initial defect is below the threshold for crack growth. By introducing a reduction term in the typical formulation of the threshold for crack growth, the authors recently proposed a general phenomenological model, which can effectively describe crack growth from internal defects in VHCF. The model is able to consider the different crack growth scenarios that may arise in VHCF and is enough general to embrace the various weakening mechanisms proposed in the literature for explaining why crack can grow below the threshold.

In the present paper, the model is generalized in a statistical framework. The statistical distributions of the crack growth threshold and of the initial defect size are put into the model. The procedure for the estimation of the Probabilistic‐S‐N curves and of the fatigue limit distribution is illustrated and numerically applied to an experimental dataset.
Amino acid composition, antioxidant and functional properties of protein hydrolysates from the roe of rainbow trout (Oncorhynchus mykiss)
Authors: Rajabzadeh Mahsa , Pourashouri Parastoo , Shabanpour Bahare , Alishahi Alireza
Published: September 2017

A fish roe protein hydrolysate from rainbow trout (Oncorhynchus mykiss) trout roe protein hydrolysates (TRH) was produced by pepsin and Alcalase. Proximate, amino acid compositions, protein digestibility and molecular mass distribution of the hydrolysates were determined. The degree of hydrolysis was found to be 44.08% and 27.62% (pepsin and Alcalase, respectively). The two hydrolysates contained a high amount of essential amino acids (33.53% Alcalase–29.39% pepsin). The results showed that TRH by different enzymes is a good source of the leucine and lysine amino acids. The pepsin produced a white powder with higher brightness (L* = 89.50). Alcalase hydrolysate was brownish yellow in colour (L* = 52.85, a* = 10.30, b* = 26.25). The hydrolysates represented excellent antioxidant activities in various concentrations. TRHs showed a good foaming and emulsification properties. The results thus revealed that protein hydrolysates from rainbow trout roe could be used as food additives possessing essential amino acids and antioxidant activity.
MUCOID IMPACTION OF THE BRONCHI
Authors: HARVEY COTTER , BLACKET R. B. , READ JOHN
Published: September 2017

Seven cases illustrating the syndrome of mucoid impaction of bronchi are described. The syndrome seems to be confined to asthmatics. It may be clinically silent for long periods, or it may lead to bronchiectasis, pulmonary infection and hæmoptysis. Radiologically it may show both peripheral and hilar components. Diagnostically it may be confused with pulmonary tuberculosis, neoplasm or Loeffler's syndrome.

Treatment is primarily medical. Adrenal corticoids may aggravate infection and are contraindicated. Surgical resection may be necessary to remove areas of destroyed lung or when a differentiation from bronchial carcinoma is impossible on clinical grounds.

Lobectomy was performed in two cases only in this series, and the examination of operation specimens showed bronchi occluded by eosinophilic mucous material. There was inflammation with disorganization of the bronchial walls, and the alveoli showed collapse and lipoid pneumonia.

It is considered that the syndrome described represents a more benign and localized variant of the widespread mucus obstruction of small bronchi found in fatal cases of status asthmaticus, and that both have their basis in a quantitative or qualitative disorder of bronchial mucus secretion in asthmatics. This disorder may be present even when clinical asthma is temporarily absent.
A NOTE ON A B O BLOOD GROUP DISTRIBUTION IN CARCINOMA OF THE ŒSOPHAGUS AND CARDIA
Authors: BILLINGTON B. P.
Published: September 2017

In 119 cases of squamous carcinoma of the œsophagus the A B O blood group distribution has not shown significant difference from that of a control population.

The A B O blood group distribution in 86 cases of carcinoma of the cardia of the stomach appears to show a significant difference from that of a control population, the incidence of group A being 19.7% above the expected value.
MEGALOBLASTIC ANÆMIA ASSOCIATED WITH ANTICONVULSANT DRUG THERAPY
Authors: STOKES JOHN B. , FORTUNE CYRIL
Published: September 2017

An epileptic boy of 16 years developed megaloblastic anæmia while being treated with primidone and phenytoin. There was an optimal hæmatological response to folic acid therapy. Laboratory investigations showed a normal serum concentration of vitamin B12 and normal radioactive vitamin B12 absorption. This is the thirty‐third reported case of megaloblastic anæmia associated with anticonvulsant therapy.

Certain features common to the majority of these cases suggest that a folic acid deficiency or a derangement of folic acid metabolism is responsible for the megaloblastic anæmia. All 20 patients treated with folic acid responded optimally. Eight patients are reported to have responded to vitamin B12, one to liver extract and four to a combination of folic acid and vitamin B12.

It is suggested that the anticonvulsant drugs have an antifolic acid action which is too mild to produce megaloblastic anæmia in the majority of epileptics unless one or more co‐factors operate. A suboptimal folic acid intake is postulated as the main co‐factor in at least five of the 20 cases in which there was a response to folic acid and perhaps also in some of the cases in which a response has been reported to vitamin B12. In one case repeated hæmorrhage, in another pregnancy and in a third case a possible latent steatorrhœa are postulated as additional co‐factors.
Pricing and inventory strategies under quick response with strategic and myopic consumers
Authors: Wang Xuantao , Ma Peng , Zhang Yulin
Published: September 2017

We divide consumers in the selling period into two types according to their purchasing behavior: strategic customers and myopic customers. We address the optimal inventory and pricing decision problem of a retailer considering strategic and myopic consumers with and without a quick response. The results indicate that the retailer should establish a higher price to sell only to myopic customers if there is a sufficient presence of myopic customers in the market, and the retailer should set a lower price to sell to myopic and strategic customers if the number of myopic customers in the market is relatively low. A quick response can decrease the initial ordering quantity and increase the retailer's profit when selling only to myopic customers or selling to both myopic and strategic customers. Moreover, a quick response is beneficial for the retailer to improve the product's retail price if the retailer wishes the two types of customers to purchase the product during the selling period. We also find that the pricing strategy considering strategic and myopic consumers under a quick response will increase profits more than the pricing strategy only considering myopic customers. Finally, numerical experiments are conducted to illustrate and validate the proposed models and provide managerial insights.
Lectin BS‐I inhibits cell migration and invasion via AKT/GSK‐3β/β‐catenin pathway in hepatocellular carcinoma
Authors: Jian Qiang , Yang Zhao , Shu Jian , Liu Xiawei , Zhang Jing , Li Zheng
Published: September 2017

Hepatocellular carcinoma (HCC) is most common malignant cancer worldwide; however, the mortality rate of HCC remains high due to the invasion and metastasis of HCC. Thus, exploring novel treatments to prevent the invasion of HCC is needed for improving clinical outcome of this fatal disease. In this study, we identified lectin from Bandeiraea simplicifolia seeds (BS‐I) binds to metastasis‐associated HCC cell surface glycans by a lectin microarray and inhibits HCC cell migration and invasion through downregulating the matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9) and urokinase‐type plasminogen activator (uPA) production. These effects of BS‐I were mediated by inhibiting the activation of AKT/GSK‐3β/β‐catenin pathway and depended on specificity of lectin BS‐I binding to GalNAc. GSK3β inhibitors rescued BS‐I‐mediated inhibition of migration and invasion of HCC cell. Further, we identified that lectin BS‐I interacts with sGrp78, affects membrane localization of sGrp78 and attenuates the binding of sGrp78 and p85 to inhibit the activation of AKT/GSK‐3β/β‐catenin pathway. Overexpression of Grp78 or P85 rescues BS‐I‐mediated inhibition of migration and invasion of HCC cell. These findings demonstrated for the first time that BS‐I can act as a novel potential drug to prevent the invasion of HCC.
Ligature‐induced peri‐implantitis and periodontitis in mice
Authors: Hiyari Sarah , Wong Ryan L. , Yaghsezian Aline , Naghibi Azadi , Tetradis Sotirios , Camargo Paulo M. , Pirih Flavia Q.
Published: September 2017

Aim

Peri‐implantitis (PI), inflammation around dental implants, shares characteristics with periodontitis (PD). However, PI is more difficult to control and treat, and detailed pathophysiology is unclear. We aimed to compare PI and PD progression utilizing a murine model.

Materials and Methods

Four‐week‐old male C57BL/6J mice had their left maxillary molars extracted. Implants were placed in healed extraction sockets and osseointegrated. Ligatures were tied around the implants and second molars. Controls did not receive ligatures. Mice were sacrificed 1 week, 1 and 3 months (n ≥ 5/group/time point) post‐ligature placement. Bone loss analysis was performed. Histology was performed for: haematoxylin and eosin (H&E), tartrate‐resistant acid phosphatase (TRAP), matrix metalloproteinase‐8 (MMP‐8), nuclear factor kappa‐light‐chain enhancer of activated B cells (NF‐κB), toluidine blue and calcein.

Results

PI showed statistically greater bone loss compared to PD at 1 and 3 months. At 3 months, 20% of implants in PI exfoliated; no natural teeth exfoliated in PD. H&E revealed that alveolar bone surrounding implants in PI appeared less dense compared to PD. PI presented with increased osteoclasts, MMP‐8 and NF‐κB, compared to PD.

Conclusion

PI exhibited greater tissue and bone destruction compared to PD. Future studies will characterize the pathophysiological differences between the two conditions.