bluuebunny/crossref_metadata_2025 huggingface dataset:
Electoral volatility and parties’ ideological responsiveness
Authors: DASSONNEVILLE RUTH
Published: January 2018

For a number of decades now, scholars have been indicating that ties between citizens and parties are eroding. As a consequence, electoral behaviour has become more volatile and also more unpredictable. The consequences of this process of change on parties’ strategic behaviour have, however, received little attention. In this article, the impact of dealignment on parties’ strategic behaviour is examined, with the focus being on the extent to which parties are responsive to the mean voter. The expectation of dealignment allowing parties ‘to move around more freely’ leads to the hypothesis that parties are more responsive in a context of dealignment. The analyses provide evidence that is in line with this expectation. Ideological responsiveness is conditioned by the level of volatility in the electorate. The conclusion to draw from these results is that dealignment, which profoundly affects voters’ behaviour, leads parties to become more responsive to the mean voter.
Serum Endocan Levels are Associated With Paraoxonase 1 Concentration in Patients With Chronic Kidney Disease
Authors: Samouilidou Elisabeth , Bountou Eirini , Papandroulaki Fotini , Papamanolis Manolis , Papakostas Dimitris , Grapsa Eirini
Published: January 2018

Endocan is a soluble proteoglycan released by the vascular endothelium. The increase of its serum levels is associated with inflammation, endothelial dysfunction and cardiovascular events in patients with chronic kidney disease (CKD). We studied the association of serum endocan with the lipid profile of 105 CKD patients with dyslipidemia, divided in two groups, non‐dialyzed (CKD, N = 57) and hemodialysis (HD, N = 48) in comparison with 30 normal controls (NC). We also analyzed endocan in relation with the concentration of two serum HDL‐linked members of the paraoxonase (PON) family, PON1 and PON3, which have been previously found to have antiatherogenic properties. The results showed that endocan levels were significantly higher in HD patients than in CKD patients (P < 0.001) and NC (P < 0.001). PON1 was significantly decreased only in HD patients compared to NC (P < 0.001), whereas PON3 was significantly increased in both patient groups (P < 0.001). Endocan levels were significantly and positively correlated with total cholesterol and LDL‐C in CKD and additionally were negatively correlated with HDL‐C in HD group. PON1 levels were significantly correlated with endocan in both groups, while no correlation was observed for PON3 in either group. Multiple regression analysis between endocan and the above lipid parameters in the total of patients revealed that endocan was independently associated only with PON1 (β = −0.513, P = 0.002). It is concluded that the increase of serum endocan levels in patients with CKD may be associated with the decrease of PON1 concentration, irrespective of lipid alterations produced by atherosclerosis development.
Influence of Selected Saccharomyces and Schizosaccharomyces Strains and Their Mixed Cultures on Chemical Composition of Apple Wines
Authors: Satora Paweł , Semik‐Szczurak Dorota , Tarko Tomasz , Bułdys Andrzej
Published: January 2018

Currently in apple winemaking, pure cultures of Saccharomyces cerevisiae and S. bayanus strains are mainly used. The aim of this study was to determine the influence of Saccharomyces cerevisiae (Johannisberg Riesling – LOCK 105), S. bayanus (DSMZ 3774), S. paradoxus (CBS 7302), and Schizosaccharomyces pombe (DSMZ 70576) applied in pure and mixed cultures on the chemical composition and sensory profile of apple wines. Pasteurized Gloster apple musts with addition of sucrose (up to 22°Blg) were inoculated with specific volume (0.6 g dry weight per liter) of yeast pure or mixed cultures (in a ratio of 1:1, 1:1:1, or 1:1:1:1) and fermented for 28 d at 22 °C. The influence of pure/mixed culture on the chemical composition, volatile profile, and sensory properties of apple wines was determined using high‐performance liquid chromatography (HPLC) and gas chromatography (GC) methods.

All pure culture of yeasts used for the apple wines production are characterized by good enological profiles. S. bayanus and Sch. pombe are the most distinct to S. cerevisiae. S. bayanus strain increases the level of malic acid and carbonyl compounds in apple wines, whereas Sch. pombe highly deacidifies it and produces the most of glycerol, esters, and acetic acid. The wines obtained with these 2 species gained also, respectively, the best and the worse notes during sensory analysis.

Mixed cultures (in most cases) produce greater amounts of ethanol, methanol, and volatile esters compared to pure cultures. The presence of S. bayanus in the mixed culture is beneficial for the quality of apple wines.

Practical Application

Good understanding of the properties of yeasts and the procedures for their selection will make it easier to find strains that could improve the quality of wine. Since wine is formed by the action of a number of species and strains of yeasts, many authors have studied the effect of mixed cultures on the final quality of the product. Most of this research was focused on the effect of the inoculation of Saccharomyces yeast with other species on the aroma of wine. However, there is a little data on the fermentation using simultaneous inoculation of different strains of S. cerevisiae.
Motivation to reduce alcohol consumption and subsequent attempts at reduction and changes in consumption in increasing and higher‐risk drinkers in England: a prospective population survey
Authors: de Vocht Frank , Brown Jamie , Beard Emma , West Robert , Michie Susan , Campbell Rona , Hickman Matthew
Published: January 2018

Aims

To assess how far motivation to reduce alcohol consumption in increasing and higher‐risk drinkers in England predicts self‐reported attempts to reduce alcohol consumption and changes in alcohol intake during the following 6 months.

Methods

This study used self‐reported data from 2928 higher‐risk drinkers in the Alcohol Toolkit Study (ATS): a series of monthly cross‐sectional household surveys of adults aged 16+ years of age in England. Alcohol consumption was measured in an initial survey and in a 6‐month telephone follow‐up interview using the Alcohol Use Disorders Identification Test (AUDIT)‐C questionnaire. Motivation was measured in the initial survey using the Motivation to Reduce Alcohol Consumption (MRAC) scale. Attempts to reduce alcohol consumption during the past 6 months were recorded at follow‐up. Data were analysed using repeated‐measures difference‐in‐differences and logistic regression models.

Results

Participants with higher initial motivation to reduce alcohol consumption were more likely to report that they had made an attempt to reduce consumption at follow‐up [adjusted odds ratio (ORadj) = 2.39, 95% confidence interval (CI) = 1.75–3.29]. There was an overall reduction in alcohol consumption between initial survey and follow‐up (ORadj = 0.72, 95% CI = 0.65–0.79), but there was insufficient evidence of an additional effect of motivation to reduce consumption on subsequent changes in alcohol consumption, with the difference‐in‐differences effect instead suggesting an average increase (ORadj = 1.37, 95% CI = 1.00–1.88).

Conclusions

Increasing and higher‐risk drinkers in England who report greater motivation to reduce their consumption are more likely to report making an attempt to reduce during the next 6 months, but this may not be associated with a reduction in alcohol consumption.
Health behaviours and quality of life in independently living South Australians aged 75 years or older
Authors: Amarasena N , Keuskamp D , Balasubramanian M , Brennan DS
Published: January 2018

Background

This study evaluated the associations between oral and general health behaviours, self‐reported health and quality of life of adults aged 75 years or older living independently in South Australia.

Methods

A cross sectional study based on a self‐report mailed questionnaire was conducted in 590 independently living adults aged 75 years or older. Self‐ratings of oral health and general health were assessed using single‐item global ratings. Quality of life was measured using the Oral Health Impact Profile and the EuroQol instrument for health utility.

Results

The overall response rate was 78%. The current analyses were restricted to 354 dentate older adults. Increasing age and being female were negatively associated with EuroQol scores. Good self‐rated oral and general health were more prevalent in participants with higher social status who also had lower oral health impact and higher EuroQol scores. Good self‐rated oral and general health were less prevalent while oral health impact was greater in participants who ate few fruits, vegetables or dairy products.

Conclusions

Self‐rated health and quality of life were poor in older adults with inadequate fruit/vegetables/dairy intake and lower social status. These findings suggest that nutrition and socioeconomic factors may be important to the oral and general health of adults aged 75 years or older.
Different aberrant expression pattern of immune checkpoint receptors in patients with PTCL and NK/T‐CL
Authors: Liao Ziwei , Lv Xuewen , Liu Sichu , He Zifan , Chen Shaohua , Wang Liang , Li Wenyu , Li Yangqiu
Published: January 2018

Aim

To better understand the T‐cell immunodeficiency status in patients with peripheral T‐cell lymphomas (PTCLs) and NK/T‐cell lymphomas (NK/T‐CLs), the T‐cell inhibitory receptors expression pattern was investigated.

Methods

The expression levels of programmed death 1 (PD‐1), cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4), B/T lymphocyte attenuator (BTLA), lymphocyte‐activation gene 3 (LAG‐3), T‐cell immunoglobulin‐3 (TIM‐3), T‐cell immunoglobulin and ITIM domain (TIGIT) genes were detected in peripheral blood mononuclear cells (PBMCs) from patients and healthy volunteers by quantitative real‐time‐PCR, the correlation between different gene expression levels was analyzed.

Results

Significantly higher expression of PD‐1, CTLA‐4, BTLA, LAG‐3, TIM‐3 and TIGIT can be observed as a common characteristic in patients with PTCL or NK/T‐CL. However, the coexpression pattern seemed different between subtypes. Their overexpression is also related to disease progression stage.

Conclusion

We first characterized the expression pattern of six T‐cell inhibitory receptor genes in PTCL and NK/T‐CL, which might work as immune biomarkers for evaluation the immunosuppression status and help to establish the precision targets of immunotherapy.
Age‐related change and sex difference over 60s in disc‐fovea angle in Japanese population: the Nagahama Study
Authors: Miyata Manabu , Yoshikawa Munemitsu , Ohtsuki Hiroshi , Muraoka Yuki , Hata Masayuki , Yokota Satoshi , Fujimoto Masahiro , Miyake Masahiro , Tabara Yasuharu , Matsuda Fumihiko , Yoshimura Nagahisa ,   Nagahama Study Group
Published: January 2018

Purpose

To analyse the disc‐fovea angle (DFA) by age group and to compare sex differences in each age group in a large cohort population.

Methods

This community‐based cross‐sectional cohort study included 9682 eyes of 9682 volunteers (aged 30–75 years). We measured the DFA, which is the angle between a horizontal line and a line connecting the fovea with the centroid of an optic disc on fundus photographs of the right eye. We manually marked the fovea and surrounded the optic disc. The centroid of an optic disc and the DFA was automatically calculated using originally developed software. We compared the DFA between age groups in 10‐year increments and investigated sex differences of DFA in each age group.

Results

Overall mean DFA was 6.32 ± 3.53°. The DFA of older subjects was significantly larger than that of younger subjects (p < 0.001). The DFA of women was larger than that of men in their 60s and 70s (p < 0.001 for both), but not in subjects in their 30s, 40s and 50s.

Conclusion

Larger DFA in women than in men in their 60s and 70s suggests the possibility that age‐related excyclo‐shift occurs more easily in postmenopausal women compared to men of the same age.
Increased endothelin‐1‐mediated vasoconstriction after organ culture in rat and pig ocular arteries can be suppressed with MEK/ERK1/2 inhibitors
Authors: Blixt Frank W. , Haanes Kristian Agmund , Ohlsson Lena , Tolstrup Christiansen Anders , Warfvinge Karin , Edvinsson Lars
Published: January 2018

Purpose

Even though retinal vascular changes following ischaemia have been poorly understood, the upregulation of vasoconstrictive endothelin‐1 (ET‐1) receptors (ETA/ETB) following global cerebral ischaemia has been described. The aim of this study was to investigate whether or not the MEK/ERK1/2 pathway is involved in the observed upregulation and whether specific MEK/ERK1/2 inhibitors U0126 and trametinib can prevent it.

Methods

The aim was also to localize ETA and ETB receptors using immunohistochemistry in both fresh rat ophthalmic arteries and after 24‐hr organ culture and study the receptors functionally using myography. Pig retinal arteries also underwent 24‐hr organ culture to validate similar responses across species and the retinal vasculature.

Results

Results showed that following organ culture there is a significant increase in ET‐1‐mediated vasoconstriction, in particular via the ETB receptor. Furthermore, immunohistochemistry revealed a clear increase in pERK in the smooth muscle cells of rat ophthalmic artery. U0126 and trametinib were successful in attenuating the functional vasoconstriction in both rat and pig, as well as restoring immunofluorescence of pERK to fresh levels and counteracting ETB expression in the smooth muscle cells of the rat ophthalmic artery.

Conclusion

This is the first study to show that the MEK/ERK1/2 pathway in responsible for the increase in functional vasoconstriction via ET‐1 receptor in rat ophthalmic and pig retinal arteries. Furthermore, this study is the first to suggest a way of inhibiting and preventing such an increase. With these results, we suggest a novel approach in retinal ischaemia therapy.
Autoimmunity in uveitis
Authors: ten Berge Josianne C. , Schreurs Marco W. J. , van Daele Paul L. A. , Rothova Aniki
Published: January 2018

Purpose

Recent insights into the pathogenesis of immune‐mediated diseases proposed a new classification, which includes autoimmune and auto‐inflammatory diseases. The prevalence of specific autoimmune and auto‐inflammatory diseases in uveitis and/or scleritis is not yet known. In this study, we examine the presence of systemic immune‐mediated diseases in patients with uveitis and/or scleritis and put a special emphasis on autoimmune disorders by reporting on their clinical manifestations and visual prognosis.

Methods

In this retrospective study, we reviewed data of 1327 patients presenting with uveitis and/or scleritis between January 2010 and July 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. All patients with noninfectious uveitis and/or scleritis were classified according to novel criteria for immune‐mediated diseases. Various clinical data, including visual acuity (VA), of patients with uveitis of autoimmune origin were registered during 5‐year follow‐up.

Results

The origin of uveitis was in 5% (62/1327) autoimmune, in 15% (197/1327) auto‐inflammatory and in 14% (180/1327) mixed autoimmune/auto‐inflammatory. Patients with classical autoimmune connective tissue disease (N = 17) suffered mostly from rheumatoid arthritis and granulomatosis with polyangiitis and exhibited predominantly scleritis (53%). After 5 years of follow‐up, none of the eyes of these patients developed legal blindness (VA of <0.1). The VA in patients with uveitis associated with autoimmune neuro‐ophthalmological diseases (multiple sclerosis and neuromyelitis optica; N = 27) remained stable over time.

Conclusion

Uveitis and scleritis of autoimmune origin were observed in 5% of the total series. The term autoimmune uveitis should not be used as a synonym for intraocular inflammation of noninfectious origin.
Prevalence of optical coherence tomography detected vitreomacular interface disorders: The Maastricht Study
Authors: Liesenborghs Ilona , De Clerck Eline E.B. , Berendschot Tos T.J.M. , Goezinne Fleur , Schram Miranda T. , Henry Ronald M.A. , Stehouwer Coen D.A. , Webers Carroll A.B. , Schouten Jan S.A.G.
Published: January 2018

Purpose

To calculate the prevalence of all vitreomacular interface (VMI) disorders and stratify according to age, sex and (pre)diabetes status.

Methods

The presence of VMI disorders was assessed in 2660 participants aged between 40 and 75 years from The Maastricht Study who had a gradable macular spectral‐domain optical coherence tomography (SD‐OCT) volume scan in at least one eye [mean 59.7 ± 8.2 years, 50.2% men, 1531 normal glucose metabolism (NGM), 401 prediabetes, 728 type 2 diabetes (DM2, oversampled)]. A stratified and multivariable logistic regression analysis was used.

Results

The prevalence of the different VMI disorders for individuals with NGM, prediabetes and DM2 was, respectively, 5.7%, 6% and 6.7% for epiretinal membranes; 6%, 9.6% and 6.8% for vitreomacular traction; 1.1%, 0.7% and 0.3% for lamellar macular holes; 0.1%, 0% and 0% for pseudoholes; 1.1%, 1.9% and 5.5% for macular cysts. None of the participants was diagnosed with a macular hole. The prevalence of epiretinal membranes, vitreomacular traction and macular cysts was higher with age (p < 0.001). Vitreomacular traction and lamellar macular holes were more frequent in women (p < 0.01). DM2 is positively associated [OR = 3.9 (95% CI 2.11–7.22, p < 0.001)] with macular cysts and negatively associated with lamellar macular holes [OR = 0.2 (95% CI 0.04–0.9, p = 0.036)] after adjustment for age and sex. The calculated prevalence of VMI disorders was 15.9%.

Conclusions

The calculated prevalence of VMI disorders in individuals aged between 40 and 75 years is 15.9%. The prevalence depends on age, sex and glucose metabolism status for several types of VMI disorders.
Age‐related changes in with‐the‐rule and oblique corneal astigmatism
Authors: Næser Kristian , Savini Giacomo , Bregnhøj Jesper Flethøj
Published: January 2018

Purpose

To describe the age‐related changes in with‐the‐rule (WTR) and oblique keratometric astigmatism (KA), posterior corneal astigmatism (PCA) and total corneal astigmatism (TCA).

Methods

We used a Pentacam HR (high‐resolution) rotating Scheimpflug camera to determine the KA, PCA and TCA in the right eyes of 710 patients, aged from 20 to 88 years. The age‐related changes along the vertical, horizontal and oblique meridians were analyzed with Næser′s polar value method in a cross‐sectional study.

Results

In the whole group, all meridional astigmatic powers and polar values were stable in the age groups from 20 to 49 years, followed by a 1.0 dioptre (D) against‐the‐rule (ATR) change in KA and TCA, and a 0.12 D reduction in against‐the‐rule PCA. A nasal rotation of the steep meridian in KA and TCA was noted in the 70–88 years old. The PCA averaged approximately 0.25 D ATR in all age groups. Females displayed the same early astigmatic stability as in the whole group, while male eyes demonstrated a linear decay from 1.5 D WTR at 20 years to 0.5 D ATR astigmatism for the oldest patients.

Conclusion

Corneal astigmatism is stable until the age of 50 years; thereafter both keratometric and total corneal astigmatism show a 0.25 D ATR change per 10 years. The average 0.25 D ATR PCA compensates the predominant keratometric WTR astigmatism in the younger patients and increases the TCA in the elderly with keratometric ATR astigmatism. The gender‐based differences in age‐related astigmatism require further studies.
Pharmacogenetics of Risperidone‐Induced Insulin Resistance in Children and Adolescents with Autism Spectrum Disorder
Authors: Sukasem Chonlaphat , Vanwong Natchaya , Srisawasdi Pornpen , Ngamsamut Nattawat , Nuntamool Nopphadol , Hongkaew Yaowaluck , Puangpetch Apichaya , Chamkrachangpada Bhunnada , Limsila Penkhae
Published: January 2018

The purpose of this study was to explore the association of genetic polymorphism of genes related to pharmacokinetics or pharmacodynamics with insulin resistance in children and adolescents with autism spectrum disorder (ASD) and treated with risperidone. All 89 subjects underwent measurement of fasting blood glucose and insulin levels, body‐weight and height. Genotyping was performed by TaqMan real‐time polymerase chain reaction (PCR) (pharmacokinetics genes: cytochrome P450 2D6 (CYP2D6) *4 (rs3892097), *5 (gene deletion), *10 (rs1065852) and *41 (rs28371725), ATP‐binding cassette transporter B1 (ABCB1) 2677 G>T/A (rs2032582) and 3435C>T (rs1045642) and pharmacodynamics genes: dopamine receptor D2 (DRD2) Tag‐SNP (C>T) (rs4436578), DRD2 Tag1A (C>T) (rs1800497), leptin gene (LEP) ‐2548G>A (rs7799039), ghrelin gene (GHRL) ‐604G>A (rs27647) and brain‐derived neurotrophic factor (BDNF) 196G>A (rs6265)). Drug levels were analysed by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The results revealed that 5 (5.62%) patients presented with hyperglycaemia. Insulin resistance was detected in 15 (16.85%) patients. Insulin resistance was associated with LEP 2548 G>A and BDNF 196 G>A polymorphism (p = 0.051 and p = 0.03). There was no association of pharmacokinetic gene polymorphisms (CYP2D6 and ABCB1) and risperidone levels with insulin resistance. Multiple regression analysis indicated that BDNF 196 G>A polymorphism was significantly associated with insulin resistance (p = 0.025). This finding suggested that BDNF 196 G>A polymorphism may be a genetic marker for predicting insulin resistance before initiating treatment in patients treated with risperidone. Because of the small sample size, further studies are needed to confirm these results.
Brief Challenges on Medicinal Plants: An Eye‐Opening Look at Ageing‐Related Disorders
Authors: Bjørklund Geir , Dadar Maryam , Martins Natália , Chirumbolo Salvatore , Goh Bey Hing , Smetanina Kateryna , Lysiuk Roman
Published: January 2018

Several studies have reported that nature‐derived antioxidants may prevent free radicals over‐production and therefore control the onset and prevent the exacerbation of different kinds of diseases caused by oxidative stress and redox‐derived stressors, including ageing, fundamentally by suppressing the oxidative by‐products‐mediated degradation. Naturally derived antioxidants exert their anti‐ageing action via a panoply of signalling systems, many of which engaging reactive oxygen and nitrogen species scavenging, with the Nrf2/Keap1‐ARE system and improving the many survival genes and functions (such as the pathway mTOR/Foxo/SIRT1) able to slow cellular senescence. Most of the research in this field has evaluated the regulative effects and even pathways of herbal extracts with antioxidant property in the ageing process, and various age‐related disorders such as cardiovascular disease, ischaemia‐reperfusion injury, coronary and myocardial circulatory perfusion, peripheral vascular resistance, and even neurodegenerative disorders are prevented plant phytochemicals often via their antioxidant potential. A much more complex ability to interact with survival functions makes these compounds successfully active in preventing ageing‐related disorders. This report aimed to discuss in more detail some selected medicinal plants including Allium sativum, Aloe vera, Crataegus spp., Cynara scolymus, Eleutherococcus senticosus, Ginkgo biloba, Hippophae rhamnoides, Panax ginseng, Rosmarinus officinalis, Schizandra chinensis, Vitis vinifera and seaweeds in the prevention of ageing‐related pathologies. A systematic overview of the relevant information in the antioxidant function of the many herbal products reviewed here for the control of the ageing process is proposed, to provide a new horizon on the design of anti‐ageing herbal medicines.
Why arguments against infanticide remain convincing: A reply to Räsänen
Authors: Rodger Daniel , Blackshaw Bruce P. , Wilcox Clinton
Published: January 2018

In ‘Pro‐life arguments against infanticide and why they are not convincing’ Joona Räsänen argues that Christopher Kaczor's objections to Giubilini and Minerva's position on infanticide are not persuasive. We argue that Räsänen's criticism is largely misplaced, and that he has not engaged with Kaczor's strongest arguments against infanticide. We reply to each of Räsänen's criticisms, drawing on the full range of Kaczor's arguments, as well as adding some of our own.
Using public surveys to reliably and rapidly estimate the distributions of multiple invasive species on the Andaman archipelago
Authors: Mohanty Nitya Prakash , Sachin Anand , Selvaraj Gayathri , Vasudevan Karthikeyan
Published: January 2018

To effectively manage multiple biological invasions, information on their distributions must be generated rapidly and over large spatial scales. Using public surveys in a false‐positive occupancy framework, we reliably estimate the distributions of three synanthropic invasive species on the Andaman Islands.
Development of Parent–Adolescent Relationships: Conflict Interactions as a Mechanism of Change
Authors: Branje Susan
Published: January 2018

Adolescence is a period of rapid biological and psychosocial changes, which have a salient impact on parent–child relationships. Parents and adolescents have to reorganize responsibilities and move toward a more egalitarian relationship. Although conflicts between parents and children become more frequent and more intense during adolescence, these conflicts are also thought to be a means to negotiate relational changes. The short‐term dyadic processes that occur during conflict interactions are important in the development of parent–adolescent relationships. Parent–adolescent dyads with more emotional variability during conflict interactions tend to adapt effectively and reorganize their relationships in response to the developmental needs of adolescents. Thus, parent–adolescent conflicts are adaptive for relational development when parents and adolescents can switch flexibly between a range of positive and negative emotions.
Birth order and paediatric allergic disease: A nationwide longitudinal survey
Authors: Kikkawa T. , Yorifuji T. , Fujii Y. , Yashiro M. , Okada A. , Ikeda M. , Doi H. , Tsukahara H.
Published: January 2018

Background

Environmental factors seem to be related to the incidence of allergic disease. Children with a later birth order are often exposed to environments, where pathogens and endotoxins can be found, and thus have a higher risk of developing infectious diseases. Therefore, birth order is regarded as an indicator that reflects post‐natal environment. However, longitudinal studies are limited on this subject. This study sought to elucidate the relationships between birth order and allergic disease.

Methods

From a nationwide longitudinal study that followed children born in 2001 (n = 47 015), we selected doctors’ visits for 3 types of allergic disease—bronchial asthma, food allergy and atopic dermatitis—from infancy to 12 years of age and conducted binomial log‐linear regression analysis to evaluate the associations between birth order and these diseases. We adjusted for the child and parental factors and estimated risk ratio (RR) and 95% confidence interval (CI) for each outcome.

Results

The associations between birth order and bronchial asthma were diverse; later birth order increased the risk in early childhood, but decreased the risks during school age. For example, the adjusted RR comparing third‐born or higher and first‐born children was 1.19 (95% CI, 1.05‐1.35) between 30 and 42 months of age, but was 0.76 (95% CI, 0.65‐0.89) between 10 and 11 years. Later birth order was generally protective for food allergy but increased the risk of atopic dermatitis.

Conclusion

The influence of birth order depended on the type of allergic disease and the childhood period. Childhood is unique in terms of physical and immunological development, and the immune response to the post‐natal environment in childhood appears to be heterogeneous.
Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual‐release hydrocortisone treatment: a 36‐month retrospective analysis
Authors: Guarnotta Valentina , Ciresi Alessandro , Pillitteri Giuseppe , Giordano Carla
Published: January 2018

Objective

Dual‐release hydrocortisone (DR‐HC) provides physiological cortisol exposure, leading to an improvement of anthropometric and metabolic parameters. The aim of the study was to evaluate the effects of DR‐HC on insulin secretion and sensitivity and cardiometabolic risk, indirectly expressed by the visceral adiposity index (VAI).

Design and Patients

Retrospective analysis of 49 patients, 13 with primary and 36 with secondary adrenal insufficiency (AI), respectively, on conventional glucocorticoid treatment at baseline and switched to DR‐HC for 36 months. Overall, 24 patients had AI‐pre–diabetes (impaired fasting glucose, impaired glucose tolerance and the combination), and 25 had AI‐normal glucose tolerance (NGT).

Measurements

Clinical and metabolic parameters, including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia, AUC2 h insulinaemia, oral disposition index [Dio] and ISI‐Matsuda), were evaluated.

Results

In patients with AI‐NGT and AI‐prediabetes, a significant decrease in BMI (P = .017 and P < .001), waist circumference (P = .008 and P < .001), HbA1c (P = .034 and P = .001) and a significant increase in HDL‐C (P = .036 and P = .043) was, respectively, observed. In addition, in prediabetic patients, only we found a significant decrease in insulinaemia (P = .014), AUC2 h insulinaemia (P = .038) and VAI (P = .001), in concomitance with a significant increase in DIo (P = .041) and ISI‐Matsuda (P = .038).

Conclusions

Long‐term DR‐HC therapy is associated with an improvement in insulin secretion and sensitivity in patients with prediabetes. However, all patients appear to benefit from the treatment in terms of improvement of metabolic and anthropometric parameters. Larger studies are required to confirm our preliminary data.
Serum irisin concentrations in lean adolescents with polycystic ovary syndrome
Authors: Bacopoulou Flora , Athanasopoulos Nikos , Efthymiou Vasiliki , Mantzou Aimilia , Aravantinos Leon , Vlahopoulos Spiros , Deligeoroglou Efthymios
Published: January 2018

Objective

To explore differences in irisin concentrations between lean adolescents with PCOS and age‐ and body mass index (BMI)‐matched controls and examine the associations of irisin with core features of the syndrome.

Design

Cross‐sectional study.

Patients

Lean females with PCOS, aged 13‐21 years.

Measurements

Physical, hormonal and sonographic assessment. Irisin concentrations were measured with ELISA.

Results

Participants included in total 39 sedentary females (mean ± SD; age 17.3 ± 2.1 years, BMI 20.7 ± 1.3 Kg/m2), 23 adolescents with PCOS and 16 controls. Adolescents with PCOS compared to controls had significantly elevated concentrations of fasting serum irisin (mean ± SD; PCOS, 1.7 ± 1.0 μg/mL vs controls, 1.0 ± 0.4 μg/mL; P = .007), luteinizing hormone (LH), oestradiol, testosterone, Δ4‐androstenedione, 17‐hydroxyprogesterone, glucose, as well as free androgen index, Ferriman‐Gallwey score and mean ovarian volume (MOV). For the total sample, circulating irisin was positively correlated with MOV (r = .332, P = .041), glucose (r = .428, P = .007), insulin (rs = .369, P = .021) and HOMA‐IR (rs = .422, P = .007) and negatively correlated with QUICKI (r = −.329, P = .041). Follicle‐stimulating hormone (B = 0.295, Beta = .342, P = .042) and MOV (B = 0.182, Beta = 0.821, P = .001) were positive predictors, and LH (B = −0.108, Beta = −0.523, P = .010) and testosterone (B = −0.431, Beta = −0.457, P = .032) were negative predictors of irisin concentrations, whereas irisin positively predicted fasting glucose (B = 0.262, Beta = 0.428, P = .007). In the PCOS group, irisin concentrations were positively correlated with HOMA‐IR (rs = .416, P = .048) but negatively correlated with LH (rs = −.499, P = .015), testosterone (r = −.585, P = .003), free androgen index (r = −.426, P = .048) and Ferriman‐Gallwey score (r = −.533, P = .015).

Conclusions

Irisin was associated with the adolescents' metabolic and reproductive characteristics and the hyperandrogenic phenotype of the syndrome. Much research is needed to ascertain mechanisms of elevated serum irisin in adolescent PCOS.
Genetic screening and functional analysis of CASP9 mutations in a Chinese cohort with neural tube defects
Authors: Liu Xiao‐Zhen , Zhang Qin , Jiang Qian , Bai Bao‐Ling , Du Xiao‐Juan , Wang Fang , Wu Li‐Hua , Lu Xiao‐Lin , Bao Yi‐Hua , Li Hui‐Li , Zhang Ting
Published: January 2018

Aim

Neural tube defects (NTDs) are birth defects of the nervous system and are the second most frequent cause of birth defects worldwide. The etiology of NTDs is complicated and involves both genetic and environmental factors. CASP9 is an initiator caspase in the intrinsic apoptosis pathway, which in Casp9−/− mice has been shown to result in NTDs because of decreased apoptosis. The aim of this study was to evaluate the potential genetic contribution of the CASP9 gene in human NTDs.

Methods

High‐throughput sequencing was performed to screen genetic variants of CASP9 genes in 355 NTD cases and 225 matched controls. Apoptosis‐relevant assays were performed on transiently transfected E9 neuroepithelial cells or human embryonic kidney 293T cells, to determine the functional characteristics of NTD‐specific rare variants under complete or low folic acid (FA) status.

Results

We found significant expression of CASP9 rare variants in NTDs and identified 4 NTD‐specific missense variants. Functional assays demonstrated that a p.Y251C variant attenuates apoptosis by reducing CASP9 protein expression and decreasing activity of the intrinsic apoptosis pathway. From this, we conclude that this variant may represent a loss‐of‐function mutation. A 4‐time recurrent p.R191G variant did not affect intrinsic apoptosis in complete medium, while it completely inhibited apoptosis induced by low FA medium.

Conclusion

Our findings identify a genetic link for apoptosis in human NTDs and highlight the effect of gene‐environment interactions in a complex disease.
Incapacity to control emotion in major depression may arise from disrupted white matter integrity and OFC‐amygdala inhibition
Authors: Zheng Kai‐Zhong , Wang Hua‐Ning , Liu Jian , Xi Yi‐Bin , Li Liang , Zhang Xi , Li Jia‐Ming , Yin Hong , Tan Qing‐Rong , Lu Hong‐Bing , Li Bao‐Juan
Published: January 2018

Background

Disturbances in emotion regulation are the hallmarks of major depressive disorder (MDD). The incapacity to control negative emotion in patients has been associated with abnormal hyperactivation of the limbic system and hypoactivation of the frontal cortex. The amygdala and orbital frontal cortex (OFC) are two critical regions of the emotion regulation neural systems.

Methods

This study investigated the anatomical basis of abnormal emotion regulation by tracking the fiber tracts connecting the amygdala and OFC. In addition, using dynamic casual modeling on resting‐state fMRI data of 20 MDD patients and equivalent controls, we investigated the exact neural mechanism through which abnormal communications between these two nodes were mediated in MDD.

Key Results

The results revealed disrupted white matter integrity of fiber tracts in MDD, suggesting that functional abnormalities were accompanied by underlying anatomical basis. We also detected a failure of inhibition of the OFC on the activity of the amygdala in MDD, suggesting dysconnectivity was mediated through “top‐down” influences from the frontal cortex to the amygdala. Following 8 weeks of antidepressant treatment, the patients showed significant clinical improvement and normalization of the abnormal OFC‐amygdala structural and effective connectivity in the left hemisphere.

Conclusions & Inferences

Our findings suggest that pathways connecting these two nodes may be core targets of the antidepressant treatment. In particular, it raised the intriguing question: Does the reversal of structural markers of connectivity reflect a response to antidepressant medication or activity‐dependent myelination following a therapeutic restoration of effective connectivity?
Candesartan ameliorates brain inflammation associated with Alzheimer's disease
Authors: Torika Nofar , Asraf Keren , Apte Ron N. , Fleisher‐Berkovich Sigal
Published: January 2018

Aims

Alzheimer's disease (AD) pathology is associated with brain inflammation involving microglia and astrocytes. The renin‐angiotensin system contributes to brain inflammation associated with AD pathology. This study aimed to investigate the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation of glial functions associated with AD.

Methods

Focusing on the role of candesartan in glial inflammation, we evaluated inflammatory mediators’ levels, secreted by lipopolysaccharide‐induced microglia following candesartan treatment. Also, short‐term intranasal candesartan effects on amyloid burden and microglial activation were investigated in 5 familial AD mice.

Results

Candesartan showed anti‐inflammatory effects and shifted microglial activation toward a more neuroprotective phenotype. Candesartan decreased the lipopolysaccharide‐induced nitric oxide synthase and cyclooxygenase‐2 expression levels, which was accompanied by an induction of arginase‐1 expression levels and enhanced Aβ1‐42 uptake by microglia. Moreover, intranasally administered candesartan to AD mice model significantly reduced the amyloid burden and microglia activation in the hippocampus.

Conclusions

These results thus shed light on the neuroprotective role of candesartan in the early stage of AD, which might relate to modulation of microglial activation states.
A review of dipeptidyl peptidase‐4 inhibitors. Hot topics from randomized controlled trials
Authors: Deacon Carolyn F.
Published: January 2018

The first clinical study to investigate effects of dipeptidyl peptidase‐4 (DPP‐4) inhibition was published in 2002, and since then, numerous randomized controlled trials (RCTs) have shown that DPP‐4 inhibitors are efficacious, safe and well‐tolerated. This review will focus upon RCTs which have investigated DPP‐4 inhibitors in patient groups which are often under‐represented or excluded from typical phase 3 clinical trials. Large cardiovascular (CV) safety outcome trials in patients with established CV disease have confirmed that DPP‐4 inhibitors are not associated with any additional CV risk in these already‐at‐high‐risk individuals, while raising awareness of any uncommon adverse events, such as heart failure hospitalization seen in one of the trials. Studies in patients with kidney disease have shown DPP‐4 inhibitors to be efficacious without increasing the risk of hypoglycaemia, irrespective of the degree of renal impairment, while data from the large CV trials as well as smaller RCTs have even pointed towards potential renoprotective effects such individuals. The use of DPP‐4 inhibitors with insulin when therapy requires intensification may be beneficial without affecting the incidence or severity of hypoglycaemia, with these effects also being replicated in patients with chronic kidney disease, for whom other agents may not be suitable. Attention is now turning towards exploring the potential utility of DPP‐4 inhibitors in other circumstances, including for in‐hospital management of hyperglycaemia and in other metabolic disorders. Together, these RCTs raise the possibility that in the future, DPP‐4 inhibitors may have a broader use which may extend beyond glycaemic control in the typical type 2 diabetes mellitus (T2DM) patient seen in general practice and may encompass conditions other than T2DM.
The Taiwan tea boom—a financial glut
Authors: Olds Kelly B.
Published: January 2018

In the last half of the nineteenth century, northern Taiwan experienced a boom in tea exports. This led to a large trade surplus accompanied by large inflows of silver money. The increase in the money supply did not have much effect on rice prices or consumption, but did lower interest rates. The lower interest rates and higher real money balances caused a large increase in real estate prices. This local financial glut lasted more than 20 years. Along the China coast, the banking system allowed businesses to move funds easily in and out of areas, such as northern Taiwan, but once silver reached Taiwanese farmers in the village economy, it did not flow so easily. Studies of early finance that focus on commercial networks generally overlook such problems.
A two‐path model of auditory modulation detection using temporal fine structure and envelope cues
Authors: Ewert Stephan D. , Paraouty Nihaad , Lorenzi Christian
Published: January 2018

A model using temporal‐envelope cues was previously developed to explain perceptual interference effects between amplitude modulation and frequency modulation (FM). As that model could not accurately predict FM sensitivity and the interference effects, temporal fine structure (TFS) cues were added to the model. Thus, following the initial stage of the model consisting of a linear filter bank simulating cochlear filtering, processing was split into an ‘envelope path’ based on envelope power cues and a ‘TFS path’ based on a measure of the distribution of time intervals between successive zero‐crossings. This yielded independent detectability indices for envelope and TFS cues, which were optimally combined to produce a single decision statistic. Independent internal noises in the envelope and TFS paths were adjusted to match the data. Simulations indicate that TFS cues are required to account for FM data for young normal‐hearing listeners and that TFS processing is impaired for both older normal‐hearing and hearing‐impaired listeners. The role of TFS was further assessed by relating the monaural FM sensitivity to measures of interaural phase difference, commonly assumed to rely on binaural TFS sensitivity. The model demonstrates that binaural TFS sensitivity is considerably lower than monaural TFS sensitivity. Similar to FM thresholds, interaural phase difference sensitivity declined with age and hearing loss, although higher degradations were observed in binaural temporal processing compared to monaural processing. Overall, this model provides a novel tool to explore the mechanisms involved in FM processing in the normal auditory system and the degradations in FM sensitivity with ageing and hearing loss.
Merleau‐Ponty on abstract thought in mathematics and natural science
Authors: Matherne Samantha
Published: January 2018

In this paper, I argue that in spite of suggestions to the contrary, Merleau‐Ponty defends a positive account of the kind of abstract thought involved in mathematics and natural science. More specifically, drawing on both the Phenomenology of Perception and his later writings, I show that, for Merleau‐Ponty, abstract thought and perception stand in the two‐way relation of “foundation,” according to which abstract thought makes what we perceive explicit and determinate, and what we perceive is made to appear by abstract thought. I claim that, on Merleau‐Ponty's view, although this process can sometimes lead to falsification, it can also be carried out in such a manner that allows mathematics and natural science to articulate what we perceive in a way that is non‐distortive and in keeping with the demands of perception itself.
Practical grounds for belief: Kant and James on religion
Authors: Williams Neil W. , Saunders Joe
Published: January 2018

Both Kant and James claim to limit the role of knowledge in order to make room for faith. In this paper, we argue that despite some similarities, their attempts to do this come apart. Our main claim is that, although both Kant and James justify our adopting religious beliefs on practical grounds, James believes that we can—and should—subsequently assess such beliefs on the basis of evidence. We offer our own account of this evidence and discuss what this difference means for their accounts of religious belief.
Geographical and experimental contexts modulate the effect of warming on top‐down control: a meta‐analysis
Authors: Marino Nicholas dos Anjos Cristiano , Romero Gustavo Quevedo , Farjalla Vinicius Fortes
Published: January 2018

Ecologists have extensively investigated the effect of warming on consumer–resource interactions, with experiments revealing that warming can strengthen, weaken or have no net effect on top‐down control of resources. These experiments have inspired a body of theoretical work to explain the variation in the effect of warming on top‐down control. However, there has been no quantitative attempt to reconcile theory with outcomes from empirical studies. To address the gap between theory and experiment, we performed a meta‐analysis to examine the combined effect of experimental warming and top‐down control on resource biomass and determined potential sources of variation across experiments. We show that differences in experimental outcomes are related to systematic variation in the geographical distribution of studies. Specifically, warming strengthened top‐down control when experiments were conducted in colder regions, but had the opposite effect in warmer regions. Furthermore, we found that differences in the thermoregulation strategy of the consumer and openness of experimental arenas to dispersal can contribute to some deviation from the overall geographical pattern. These results reconcile empirical findings and support the expectation of geographical variation in the response of consumer–resource interactions to warming.
Edaphic correlates of feedstock‐associated diazotroph communities
Authors: Soman Chinmay , Keymer Daniel P. , Kent Angela D.
Published: January 2018

Miscanthus × giganteus and Panicum virgatum are potential promising bioenergy feedstock crops suitable for the temperate zone. The energy efficiency and sustainability of bioenergy production could be improved by reducing their fertilizer inputs – particularly energy intensive nitrogen fertilizers. Miscanthus is known to benefit from nitrogen fixation by associative diazotrophs. However, because the effects of edaphic‐, management‐, and plant‐related factors on feedstock‐associated diazotroph communities have not yet been characterized, it is not currently possible to optimize the nitrogen contribution to feedstock crops from associated diazotroph communities. To address this critical knowledge gap, we characterized the bacterial and diazotroph communities in the rhizosphere and endophytic compartments of both species at eight research sites across Illinois. We also quantified the nifH gene abundance in the rhizosphere soil as well as a range of soil chemistry parameters at these sites. Multivariate statistical analyses revealed that diazotroph and bacterial communities in the rhizosphere varied primarily among sites, with very small differences between host species. Conversely, diazotroph and bacterial communities in the endophytic compartments differed significantly between plant species, but did not vary substantially among sites. Finally, nifH gene abundance in the rhizospheres of both species varied substantially from site to site and was positively correlated with soil iron concentration as well as soil ammonium concentration, and negatively correlated with abundance of other soil nutrients including calcium, total nitrogen, and nitrates. These results indicate the potential edaphic drivers of associative diazotroph communities in feedstock rhizospheres and suggest that manipulating bioavailable iron content in the soil is a potential direction for investigating the optimization of these communities to improve their nitrogen contribution to crops.