bluuebunny/crossref_metadata_2025 huggingface dataset:
Stacking up CRISPR against RNAi for therapeutic gene inhibition
Authors: Haussecker Dirk
Published: April 2016

Both RNA interference (RNAi) and clustered regularly‐interspaced short palindromic repeats (CRISPR) technologies allow for the sequence‐specific inhibition of gene function and therefore have the potential to be used as therapeutic modalities. By judging the current public and scientific journal interest, it would seem that CRISPR, by enabling clean, durable knockouts, will dominate therapeutic gene inhibition, also at the expense of RNAi. This review aims to look behind prevailing sentiments and to more clearly define the likely scope of the therapeutic applications of the more recently developed CRISPR technology and its relative strengths and weaknesses with regards to RNAi. It is found that largely because of their broadly overlapping delivery constraints, while CRISPR presents formidable competition for DNA‐directed RNAi strategies, its impact on RNAi therapeutics triggered by synthetic oligonucleotides will likely be more moderate. Instead, RNAi and genome editing, and in particular CRISPR, are poised to jointly promote a further shift toward sequence‐targeted precision medicines.
Grasping the nature of the cell interior: from Physiological Chemistry to Chemical Biology
Authors: Kyne Ciara , Crowley Peter B.
Published: April 2016

Current models of the cell interior emphasise its crowded, chemically complex and dynamically organised structure. Although the chemical composition of cells is known, the cooperative intermolecular interactions that govern cell ultrastructure are poorly understood. A major goal of biochemistry is to capture these myriad interactions in vivo. We consider the landmark discoveries that have shaped this objective, starting from the vitalist framework established by early natural philosophers. Through this historical revisionism, we extract important lessons for the bioinspired chemists of today. Scientific specialisation tends to insulate seminal ideas and hamper the unification of paradigms across biology. Therefore, we call for interdisciplinary collaboration in grappling with the complex cell interior. Recent successes in integrative structural biology and chemical biology demonstrate the power of hybrid approaches. The future roles of the (bio)chemist and model systems are also discussed as starting points for in vivo explorations.
Midori‐ishi Cyan/monomeric Kusabira‐Orange‐based fluorescence resonance energy transfer assay for characterization of various E3 ligases
Authors: Otsubo Ryota , Kim Minsoo , Lee Jihye , Sasakawa Chihiro
Published: April 2016

Many bacterial pathogens hijack the host ubiquitin system for their own benefit by delivering effectors with ubiquitin ligase (E3) into host cells via the type III secretion system. Therefore, screening for small compounds that selectively inhibit bacterial but not mammalian E3 ligases is a promising strategy for identifying molecules that could substitute for antibiotics. To facilitate high‐throughput screening for bacterial E3 ligase inhibitors, we developed a MiCy/mKO (Midori‐ishi Cyan/monomeric Kusabira‐Orange)‐based FRET (fluorescence resonance energy transfer) assay and validated it on Shigella IpaH E3 ligase effectors. We showed the feasibility of using the MiCy/mKO‐based FRET assay to identify the most appropriate ubiquitin‐conjugating enzymes (E2s) and determine the lysine specificity of a given E3, both hallmarks of E3 activity. Furthermore, we showed the usefulness of the FRET assay in characterizing mammalian E3 ligases, such as TNF receptor‐associated factor 6 (TRAF6) and mouse double minute 2 homologue (MDM2). In addition, we confirmed the feasibility of determining the efficiency of inhibition of E3 ligase activity using inhibitors of E1 ubiquitin‐activating enzymes, such as UBE1‐41, by measuring the IC50. Based on these results, we concluded that the MiCy/mKO‐based FRET assay is useful for characterizing E3 enzyme activity, as well as for high‐throughput E3 inhibitor screening.
Clinical Utility of the Mig‐SCog
Authors: Gil‐Gouveia Raquel , Oliveira António G. , Pavão Martins Isabel
Published: April 2016

Background

Mig‐SCog is a 9‐item questionnaire developed to quantify attack‐related cognitive complaints in migraine (M). The items relate to executive function and language, and the total Mig‐SCog score is the sum of those scales.

Objective

To evaluate the Mig‐SCog scores regarding cognitive symptoms during a variety of conditions.

Methods

We conducted a prospective comparative study of the Mig‐SCog scores (1) between migraine and tension‐type headache (TTH) patients during a headache; (2) in migraine patients between migraine attacks, non‐headache pain and pain‐free status; (3) in migraine patients during and outside a migraine attack.

Results

One hundred forty‐nine patients (98 M and 51 TTHA). Total Mig‐SCog score was higher in migraine patients than TTH (8.0 ± 4.1 vs 3.4 ± 3.2, P < .0001). Sixty‐three patients took part in the next part of the study. Migraine patients rated the Mig‐SCog higher for migraine (7.9 ± 4.6) than for non‐headache pain (2.3 ± 2.9, P < .0006) or pain‐free (1.6 ± 2.4, P < .0006). In the final phase of the study, 38 patients Mig‐SCog scores were not significantly different whether obtained during or outside an M attack (P = .26).

Conclusions

Attack‐related subjective cognitive symptoms, assessed by Mig‐SCog scores, differed between migraine and TTH patients. The Mig‐SCog scores from migraine patients were found to be higher during migraine than during non‐headache pain or pain‐free conditions. Patient scoring from memory for usual attacks was not significantly different to scoring within attacks, We believe this demonstrates negligible recall bias.
Empty Nest Couples: Lifestyles and Typology
Authors: da Silva Iara Silva , Slongo Luiz Antonio , Antunes Rohde Liliane
Published: April 2016

Lifestyle is a construct that makes it easier to understand consumers' behaviour, since it involves ways of life and results from past experiences, as well as from personal features based on current situations. It influences the consumption habits of individuals and their families. Accordingly, the aim of the current article is to analyze the lifestyle of individuals who belong to the empty nest couple group. The participants were Brazilian and chosen according to their activities, interests and opinions. Thus, we adopted the exploratory and descriptive design, and followed qualitative and quantitative aspects. According to the results, there are many lifestyles and they can be divided in three groups: the elitist, the politicized and the popular one. Elitists prioritize education and the consumption of cultural and organic products. The politicized group is aware of its political rights and duties. The popular group practices common habits such as playing soccer, watching TV shows and eating industrialized food.
Factors in the effective transfer of knowledge from multinational enterprises to their foreign subsidiaries: a Mozambican case study
Authors: Duarte Moleiro Martins José
Published: April 2016

The purpose of this article is to better understand the role of internal stakeholders in subsidiaries of multinational companies (MNCs) in order to offer potential insights into the cross‐border transfer of knowledge from those companies’ headquarters to their subsidiaries. The focus is upon subsidiaries in developing countries, here Mozambique. More specifically, the article is concerned with identifying factors that influence the learning of internal stakeholders and noting practices which seem associated with a high level of absorptive capacity and performance of subsidiaries. The starting point is evidence of ineffective transfer of knowledge by MNCs to their subsidiaries in developing countries, with consequent sub‐standard performance. The research reported involves four case studies of Portuguese companies operating in Mozambique and draws on data from interviews with senior and middle managers in the firms’ Mozambican subsidiaries. The results obtained suggest that successful knowledge transfer to overseas subsidiaries is found under the following conditions. First, the parent company knows the local context and provides a flow of relevant information. Second, application of knowledge locally is done flexibly to suit local circumstances. Next, a participatory approach is used so that local staff can see why the knowledge conveyed is necessary. Fourth, explanation and demonstration are key techniques, with major roles for on‐the‐job training, continuous improvement and training at headquarters. Finally, issues arising from local culture may need to be addressed.
The Advantages of Parental Involvement in Cognitive‐Behavioral Treatment of Childhood Obsessive‐Compulsive Disorder: A Single‐Case Example
Authors: Oldham‐Cooper Rose , Glasman David , Loades Maria
Published: April 2016

BACKGROUND

Interventions for the treatment of anxiety disorders in children have a growing evidence base. Cognitive‐behavioral therapy for the treatment of specific anxiety disorders in children and adolescents, including obsessive‐compulsive disorder, is now an established intervention. However, a question remains concerning the benefits of parental involvement in treatment. Some studies report limited or no benefit of including parents in treatment, whereas other studies have indicated additional advantages of parental involvement.

INTERVENTION

The present case report describes the treatment of an 11‐year‐old girl with obsessive‐compulsive disorder using cognitive‐behavioral therapy derived largely from the treatment approaches outlined in Carr (2006), March and Mulle (1998), and Derisley, Heyman, Robinson, and Turner (2008). The child's mother attended all sessions and also a one‐off parent‐only session toward the end of treatment. The report considers the benefits of involving the child's mother in treatment and possible factors that could suggest parental involvement is indicated in future cases.

OUTCOMES

Both child and mother, and the therapist, believed that parental involvement had been an important and useful element of treatment. Possible reasons for benefits of parental involvement were considered to be high parental anxiety at the outset of treatment, age of the client, and involvement of the parent in obsessions and compulsions.
Small‐Caliber Lead Failure After Generator Exchange
Authors: SALGADO RICARDO , MARTÍN JAVIER , MARTÍNEZ JOSÉ , ALZUETA JAVIER , VIÑOLAS XAVIER , FERNÁNDEZ JOAQUÍN , MOLINA MANUEL , PÉREZ LUISA , CALVO DAVID , GARCÍA JAVIER
Published: April 2016

Small‐Caliber Lead Failure After Generator Exchange

Introduction and Objectives

The Sprint Fidelis defibrillator lead (Medtronic) was recalled in 2007 due to an increased risk of failure. The generator exchange (GE) procedure has been associated with the development of Fidelis lead dysfunction. The aim of this study was to compare the rate of dysfunction between Sprint Fidelis and other defibrillator leads during the first year after GE.

Methods

A multicenter retrospective study involving patients from the UMBRELLA database who underwent GE with previous normal lead function and minimum follow‐up of 1 year after the procedure was performed. The incidence of lead dysfunction was determined via remote monitoring and defined as pacing impedance > 1,500 ohm, high‐voltage impedance > 100 ohm, R wave sensing under 2 mV, or the presence of VT/VF episodes classified as noise.

Results

A total of 531 patients were included (114 Fidelis). In the first year after GE, the total incidence of lead dysfunction was 3.6%. No significant differences were found between Fidelis and the others in survival analysis (3.5% vs. 3.6%, respectively, log‐rank 0.002, P = 0.962).

Conclusions

According to our results, the preventive removal/replacement of the Sprint Fidelis leads with normal function until GE is not a recommended practice since the rate of dysfunction after the procedure in this subgroup is no different compared with other defibrillator leads.
Commentary: Prospective trajectory research in adolescent suicidal behaviour – a possible basis for the development of empirically based interventions? A reflection on Adrian et al. (2016)
Authors: Apter Alan
Published: April 2016

Suicidal behaviour in adolescence is a heterogeneous set of behaviours comprising a variety of behaviours ranging from suicidal ideation, suicidal threats, suicidal gestures, nonsuicidal self‐injurious behaviour through medically nonserious to medically serious suicide attempts. Probably the most productive approach to this problem is a developmental one, taking one key concept and tracking it prospectively over the course of time through the developmental stages of adolescence. A natural starting point for such a study is that of suicidal ideation (SI). Thus, the article published in JCPP (Adrian et al. 2015) represents a major contribution to the field. The authors used the data from an important adolescent development study, the Developmental Pathways Project (DPP) to look at this problem. This editorial looks at this article in the context of other major studies in the field. The notion of discerning trajectories and following them up prospectively is a potentially major contribution to paediatric suicide research. Although obviously challenging, linking these trajectories to interventions and to suicide registers could lead to major breakthroughs in adolescent suicide prevention.
Use of machine learning to improve autism screening and diagnostic instruments: effectiveness, efficiency, and multi‐instrument fusion
Authors: Bone Daniel , Bishop Somer L. , Black Matthew P. , Goodwin Matthew S. , Lord Catherine , Narayanan Shrikanth S.
Published: April 2016

Background

Machine learning (ML) provides novel opportunities for human behavior research and clinical translation, yet its application can have noted pitfalls (Bone et al., 2015). In this work, we fastidiously utilize ML to derive autism spectrum disorder (ASD) instrument algorithms in an attempt to improve upon widely used ASD screening and diagnostic tools.

Methods

The data consisted of Autism Diagnostic Interview‐Revised (ADI‐R) and Social Responsiveness Scale (SRS) scores for 1,264 verbal individuals with ASD and 462 verbal individuals with non‐ASD developmental or psychiatric disorders, split at age 10. Algorithms were created via a robust ML classifier, support vector machine, while targeting best‐estimate clinical diagnosis of ASD versus non‐ASD. Parameter settings were tuned in multiple levels of cross‐validation.

Results

The created algorithms were more effective (higher performing) than the current algorithms, were tunable (sensitivity and specificity can be differentially weighted), and were more efficient (achieving near‐peak performance with five or fewer codes). Results from ML‐based fusion of ADI‐R and SRS are reported. We present a screener algorithm for below (above) age 10 that reached 89.2% (86.7%) sensitivity and 59.0% (53.4%) specificity with only five behavioral codes.

Conclusions

ML is useful for creating robust, customizable instrument algorithms. In a unique dataset comprised of controls with other difficulties, our findings highlight the limitations of current caregiver‐report instruments and indicate possible avenues for improving ASD screening and diagnostic tools.
Incretin‐based drugs for type 2 diabetes: Focus on East Asian perspectives
Authors: Seino Yutaka , Kuwata Hitoshi , Yabe Daisuke
Published: April 2016

Type 2 diabetes in East Asians is characterized primarily by β‐cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1, are secreted in response to meal ingestion, and enhance insulin secretion glucose‐dependently. Incretin‐based drugs, dipeptidyl peptidase‐4 inhibitors (DPP‐4i) and glucagon‐like peptide‐1 receptor agonists, that ameliorate β‐cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta‐analyses of clinical trials on DPP‐4i and glucagon‐like peptide‐1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β‐cell dysfunction. In addition, we found increased glycated hemoglobin‐lowering effects of DPP‐4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP‐4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP‐4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin‐associated hypoglycemia by DPP‐4i has gained attention with regard to the enhancement of hypoglycemia‐induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin‐based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients.
Genetics in Parkinson disease: Mendelian versus non‐Mendelian inheritance
Authors: Hernandez Dena G. , Reed Xylena , Singleton Andrew B.
Published: April 2016

Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ‐1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high‐content, integrated datasets.

image

This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ‐1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high‐content, integrated datasets.

This article is part of a special issue on Parkinson disease.
The physical health of people with schizophrenia in Asia: Baseline findings from a physical health check programme
Authors: Thongsai S. , Gray R. , Bressington D.
Published: April 2016

Accessible summary

What is known on the subject?

Physical health problems, especially cardiovascular disease and metabolic disorders are far more common in people with severe mental illness (SMI) than the general population.

While there are a considerable number of studies that have examined the physical health and health behaviours of people with SMI in Western countries, there have been few studies that have done this in Asia.

What this paper adds to existing knowledge?

Unhealthy body mass index (BMI) values were observed in 44% of Thai service users diagnosed with schizophrenia despite desirable levels of exercise and relatively good diets being reported by the majority of participants.

Being prescribed two or more antipsychotics was significantly associated with greater body weight and a higher BMI than in people prescribed only one antipsychotic.

What are the implications for practice?

Mental health professionals in Asia should be particularly aware of the additional risks of obesity that seem to be associated with antipsychotic polypharmacy when they are promoting the physical health of people with schizophrenia.

Introduction

People with schizophrenia have worse physical health than the general population, and studies in developed countries demonstrate that their health behaviours are often undesirable. However, as no similar studies have been conducted in Asian countries with emerging healthcare systems, the physical health promotion challenges in these settings is unknown.

Aim

To identify and explore relationships between cardiometabolic health risks, lifestyle and treatment characteristics in people with schizophrenia in Thailand.

Method

This cross‐sectional study reports the baseline findings from a physical health check programme using the Thai version of the Health Improvement Profile.

Results

Despite desirable levels of exercise and relatively good diets being reported by most of the 105 service users, unhealthy body mass index values were observed in 44% of participants. A BMI>23 kg/m² and central obesity was found to be most likely in women. Being prescribed antipsychotic polypharmacy was significantly associated with a higher BMI than in people prescribed monotherapy.

Implications for Practice

Mental health professionals in Asia should be aware of the additional risks of obesity that are associated with antipsychotic polypharmacy and may benefit from additional training in order that they may advocate for service users within medication reviews to minimize the potential iatrogenic effects of treatment.
Christian Science and American Literary History
Authors: Squires L. Ashley
Published: April 2016

The religious turn in American literary studies has produced new interest in religious movements from the turn of the 20th century, and due to the opening of archives, Christian Science is one possible direction that research in this area might turn. Yet until very recently, literary scholarship related to Christian Science has been extremely flawed, due mostly to over‐reliance on a few problematic sources. This article offers an overview of the issues that have impacted that research while suggesting that promising work is beginning to emerge.
Barthes for Barthes' Sake? Victorian Literature and Photography beyond Poststructuralism
Authors: Clayton Owen
Published: April 2016

Scholars of nineteenth‐century literature have been inspired by the multiplicity of connections that existed between writing and early photography. Critics have often argued that writers in Britain, America and elsewhere understood photography to be a profoundly realist practice, and as such that it stood as an analogue of literary realism. As this article demonstrates, such arguments have been enormously influenced by the Art History narrative of photography, as well as late twentieth‐century poststructuralism. Roland Barthes' Camera Lucida has been particularly prominent. Yet though it has much to say about the phenomenology of posing, as well as the affective quality of images, Barthes' ‘modest book’ makes assumptions that have been problematized in subsequent photographic scholarship. These assumptions, which include indexicality and medium specificity, support an ideology of photographic realism. This ideology has dominated comparative studies of Victorian literature and early photography, including work on Thomas Hardy and Henry James. One result has been for literary critics to overlook the nuances of particular technologies, such as the daguerreotype, and to treat nineteenth‐century photography as if it were a single medium. Another has been a privileging of modernism. This last result has been concomitant with a tendency for literary scholars to view photography solely as art. Important recent work in the history of photography has challenged the Art History narrative, but this has been slow to filter through to literary studies. This article will conclude by noting encouraging signs that this situation seems to be changing.
Genomic evidence for polyphyletic origins and interlineage gene flow within complex taxa: a case study of Picea brachytyla in the Qinghai‐Tibet Plateau
Authors: Ru Dafu , Mao Kangshan , Zhang Lei , Wang Xiaojuan , Lu Zhiqiang , Sun Yongshuai
Published: April 2016

Hybridization and introgression are believed to play important roles in plant evolution. However, few empirical studies have been designed to clarify the ways in which these processes complicate taxonomic delimitation. Recent phylogenetic studies based on a number of different DNA fragments have indicated that Picea brachytyla in the eastern Qinghai‐Tibet Plateau is polyphyletic, a finding that contrasts with traditional taxonomy based on morphological traits. We aimed to test this conflict using transcriptomic data from 26 trees collected from multiple localities for this and related species. Our phylogenomic analyses suggest that the sampled trees of P. brachytyla cluster into two distinct lineages corresponding to the two taxonomically recognized intraspecific varieties: var. brachytyla and var. complanata. However, var. complanata nested within Picea likiangensis and was sister to one of its three varieties, while var. brachytyla comprised an isolated lineage. The polyphyletic origin hypothesis was further supported by likelihood tree comparisons using Akaike's information criterion (AIC) and by coalescent analyses under the snapp model. However, our abba‐baba and ∂a∂i analyses suggest that gene flow between these two independently evolved lineages has been extensive and bidirectional. Introgression, as well as parallel evolution in the arid habitats common to both lineages, may have given rise to their morphological similarity. Our study highlights the importance of genomic evidence and the use of newly developed coalescent analysis methods for clarifying the evolutionary complexity of certain plant taxa.
Population genomic evidence for adaptive differentiation in the Baltic Sea herring
Authors: Guo Baocheng , Li Zitong , Merilä Juha
Published: April 2016

Detecting and estimating the degree of genetic differentiation among populations of highly mobile marine fish having pelagic larval stages is challenging because their effective population sizes can be large, and thus, little genetic drift and differentiation is expected in neutral genomic sites. However, genomic sites subject to directional selection stemming from variation in local environmental conditions can still show substantial genetic differentiation, yet these signatures can be hard to detect with low‐throughput approaches. Using a pooled RAD‐seq approach, we investigated genomewide patterns of genetic variability and differentiation within and among 20 populations of Atlantic herring in the Baltic Sea (and adjacent Atlantic sites), where previous low‐throughput studies and/or studies based on few populations have found limited evidence for genetic differentiation. Stringent quality control was applied in the filtering of 1 791 254 SNPs, resulting in a final data set of 68 182 polymorphic loci. Clear differentiation was identified between Atlantic and Baltic populations in many genomic sites, while differentiation within the Baltic Sea area was weaker and geographically less structured. However, outlier analyses – whether including all populations or only those within the Baltic Sea – uncovered hundreds of directionally selected loci in which variability was associated with either salinity, temperature or both. Hence, our results support the view that although the degree of genetic differentiation among Baltic Sea herring populations is low, there are many genomic regions showing elevated divergence, apparently as a response to temperature‐ and salinity‐related natural selection. As such, the results add to the increasing evidence of local adaptation in highly mobile marine organisms, and those in the young Baltic Sea in particular.
A Japanese familial ALS patient with autonomic failure and a p.Cys146Arg mutation in the gene for SOD1 (SOD1)
Authors: Hayashi Kentaro , Mochizuki Yoko , Koide Reiji , Kawata Akihiro , Homma Taku , Shimizu Toshio , Komori Takashi , Isozaki Eiji
Published: April 2016

We describe a Japanese man with familial amyotrophic lateral sclerosis (ALS) associated with a p.Cys146Arg mutation in the copper/zinc superoxide dismutase gene (SOD1). The patient developed bulbar signs followed by rapidly progressive limb muscle weakness. The prominent clinical feature was orthostatic hypotension due to autonomic failure, which occurred after he underwent tracheostomy 1 year and 3 months after the onset. Thereafter, he required mechanical ventilation and progressed to communication stage V (totally locked‐in state) 7 years after the onset. Neuropathology showed ALS with posterior column degeneration and multiple system degeneration. Severe neuronal loss in the intermediolateral nucleus was also observed. Two previously reported cases of ALS patients with autonomic failure showed severe neuronal loss in the intermediolateral nucleus in addition to degeneration of the motor neurons. Thus, autonomic failure due to neuronal loss in the intermediolateral nucleus could present in patients with ALS associated with certain mutations in SOD1.
Do baseline glucocorticoids simultaneously represent fitness and environmental quality in a declining aerial insectivore?
Authors: Madliger Christine L. , Love Oliver P.
Published: April 2016

Glucocorticoids (GCs) are often interpreted as indicators of disturbance, habitat quality, and fitness in wild populations. However, since most investigations have been unable to examine habitat variability, GC levels, and fitness simultaneously, such interpretations remain largely unvalidated. We combined a quantification of two habitat types, a manipulation of foraging ability (feather‐clipping just prior to nestling rearing), multiple baseline plasma GC measures, and multi‐year reproductive monitoring to experimentally examine the linkages between habitat quality, GCs, and fitness in female tree swallows Tachycineta bicolor. Control females experiencing the higher early‐season food resources of inland–pasture habitat laid larger clutches, but fledged an equal number but lower mass offspring compared to those in riparian–cropland habitat. Despite these differences in reproductive success, females nesting in the two habitat types did not differ in baseline GC levels at the early‐ or late‐breeding stage. Feather‐clipping reduced provisioning rate in both habitat types. However, baseline GC levels were affected in a habitat‐specific way; only individuals in inland–pasture habitats showed an increase in GCs. Despite this difference in GC levels, the manipulation did not influence offspring mass, reproductive output, adult return rate (a proxy for survival) to the following year, or reproductive success in the subsequent year. Nonetheless, regardless of treatment, individuals with higher GC levels during the late breeding stage returned in the following year with higher GC levels at incubation, indicating a long‐term effect on future GC levels. Our results indicate that environmental changes (e.g. foraging conditions) can have consequences for body condition, behaviour, and current and future baseline GC levels without concomitant influences on fitness, and that differences in fitness components between habitats may not be reflected in baseline GC levels. These results illustrate that baseline GCs may not simultaneously reflect environmental quality and fitness, potentially limiting their application in ecological and conservation settings.
Role of environmental exposures and filaggrin mutations on associations of ethnic origin with risk of childhood eczema. The Generation R Study
Authors: Elbert Niels J. , Duijts Liesbeth , den Dekker Herman T. , Jaddoe Vincent W. V. , Sonnenschein‐van der Voort Agnes M. M. , de Jongste Johan C. , Pasmans Suzanne G. M. A.
Published: April 2016

Background

The prevalence of childhood eczema varies considerably between ethnic groups. However, data from longitudinal studies remain scarce.

Methods

We examined the associations of ethnic origin with the development of eczema from birth until the age of 4 years, and whether known environmental and genetic risk factors explain these associations. This study was performed in a multiethnic population‐based prospective cohort among 5,082 children. Ethnic origin was based on the parents' country of birth. Data on physician‐diagnosed eczema were obtained by annual questionnaires. Information on environmental risk factors was mostly obtained by questionnaires. Filaggrin (FLG) mutations (2282del4, R2447X, R501X, and S3247X) were genotyped for 3,096 children. We used generalized estimating equation models to examine the associations of ethnic origin with the longitudinal odds of eczema at 6 months and 1, 2, 3, and 4 years of age overall and independently.

Results

Compared with Dutch children, Cape Verdean, Dutch Antillean, Surinamese‐Creole, and Surinamese‐Hindustani children had overall increased risks of eczema (OR (95%‐CI): 1.53 (1.15, 2.03), 1.60 (1.21, 2.12), 1.95 (1.56, 2.44), and 2.06 (1.65, 2.57), respectively). Effect estimates for the associations of Cape Verdean and Dutch Antillean origin with eczema became non‐significant after adjustment for genetic risk factors or both environmental and genetic risk factors, respectively. Surinamese‐Creole and Surinamese‐Hindustani children remained to have increased risks of eczema.

Conclusions

Cape Verdean, Dutch Antillean, Surinamese‐Creole, and Surinamese‐Hindustani children had increased risks of eczema in the first 4 years of life. Environmental and genetic risk factors partly weakened these associations.
Longitudinal pattern of multiplexed immunoglobulin E sensitization from prenatal stage to the first year of life
Authors: Wang Jiu‐Yao , Chen Chih‐Ann , Hou Yung‐I , Hsiao Wan‐Lin , Huang Ya‐Wen , Tsai Yu‐Ting , Tsai Hui‐Ju
Published: April 2016

Background

The longitudinal pattern of allergen‐specific IgE levels from the prenatal stage to early life has remained largely unexplored.

Methods

One‐hundred and three mother–infant pairs, which were part of an ongoing population‐based prospective birth cohort study of early childhood allergic diseases in Tainan, Taiwan, were included in this study. We examined the relationship of 20 allergen‐specific IgE levels with blood samples of mothers, cord blood, and infants at 12 months of age using Spearman rank correlation, Kenal τ and McNemar test, respectively.

Results

Certain degree of IgE sensitization against most 20 examined specific allergens was observed in blood samples of mothers, cord blood, and infants at 12 months of age. When we further examined the association between allergy‐related risk factors and atopy in infants at the first year of life, we found positive association between colic pain and atopy in infants at 12 months of age [adjusted odds ratios (AOR) = 3.51; 95% confidence interval (CI): 1.13–10.96; p = 0.03], and borderline significance between wheezing and atopy in infants at 12 months of age (AOR = 4.58; 95% CI: 0.89–23.50; p = 0.07).

Conclusion

The findings from this study suggest that influence of maternal allergen‐specific IgE levels on infant immune response might occur at birth and then wane in infants at 12 months of age. Positive association of colic pain and wheezing with atopy in infants at 12 months of age provides supportive evidence for the ‘Allergy March' theory of allergy development in an Asian birth cohort.
Treating IgE‐mediated diseases via targeting IgE‐expressing B cells using an anti‐CεmX antibody
Authors: Liour Sean S. , Tom Andrew , Chan Yueh‐Hsuan , Chang Tse Wen
Published: April 2016

Targeting the IgE pathway is a clinically validated strategy for treating IgE‐mediated diseases. Omalizumab, an anti‐IgE antibody, which binds to free IgE and prevents the binding of IgE to FcεRI on mast cells and basophils has been approved for severe persistent allergic asthma and chronic spontaneous (idiopathic) urticaria. The therapeutic efficacy of anti‐IgE has also been reported in allergic rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, anaphylaxis, and others. Anti‐CεmX, which binds to membrane‐bound IgE (mIgE) on IgE‐switched B cells, lyses mIgE‐expressing B lymphoblasts and prevents the allergen‐induced generation of IgE‐producing plasma cells, offers an alternative mechanism of intervening with the IgE inflammatory pathway. Because anti‐CεmX does not bind to free IgE, it can modulate the IgE pathway regardless of the serum IgE levels in treated patients. These unique pharmacologic mechanisms potentially enable anti‐CεmX to provide different clinical utilities from anti‐IgE and serve as a therapeutic and a prophylactic in some IgE‐mediated diseases, which are not adequately treated with current medicine.
The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology
Authors: Yamada Yohei , Hoshino Ken , Irie Rie , Tomita Hirofumi , Kato Mototoshi , Shimojima Naoki , Fujino Akihiro , Hibi Taizo , Shinoda Masahiro , Obara Hideaki , Itano Osamu , Kawachi Shigeyuki , Tanabe Minoru , Sakamoto Michiie , Kitagawa Yuko , Kuroda Tatsuo
Published: April 2016

The outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid‐resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995–2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re‐LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p < 0.00001). From 2008, three patients underwent LTx for cryptogenic FHF with PVI and conventional IS. PVI was well tolerated, and no relevant severe complications were observed. More strikingly, the patients who received PVI overcame biopsy‐proven immunological events and are all currently doing well with excellent graft function after more than five yr. We conclude that PVI is technically safe and effective for preventing severe rejection in pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications.
Sex differences in renin response and changes of capillary diameters after renal ischemia/reperfusion injury
Authors: Csohány Rózsa , Prókai Ágnes , Sziksz Erna , Balicza‐Himer Leonóra , Pap Domonkos , Kosik Anna , Sugár Dániel , Vannay Ádám , Kis‐Petik Katalin , Fekete Andrea , Szabó Attila J.
Published: April 2016

Activation of the RAS has a crucial role in the progression of ischemia/reperfusion‐associated CAD. The regulation of RAS differs in the two genders. However, the extent of gender differences and locations of renin production have not been revealed yet. We investigated in vivo the local renin production in the two genders during ischemia/reperfusion injury.

In male and female Wistar rats, renal ischemia was induced followed by a reperfusion period of two, eight, 16, 24, or 48 h. We applied flow cytometry to measure renin content and multiphoton imaging to visualize renin granules and changes of peritubular diameters in vivo during ischemia/reperfusion.

Renin content decreased in CD in the first eight h of reperfusion; however, after 16 h, its amount increased. In males, the production of renin was more pronounced, and the duration of vasoconstriction was longer with a subsequent phase of vessel hyperdilation compared to females.

Renal ischemia/reperfusion injury induces renin response not only in the JGA, but also in the CD segment. Renin production is more explicit in males than in females which, via increased angiotensin II production, might explain the different dynamism of renal vessel regulation between the two genders.
Further Steps towards a Theory of Descriptions as Predicates
Authors: Fara Delia Graff
Published: April 2016

Descriptions are predicates. Here, I'll take this to mean either of two basically equivalent things: that they have extensions as their semantic values, sets of entities, in the broadest sense; or that they have type‐〈e,t〉 functions as their semantic values, functions from entities, in the broadest sense, to truth values. An entity in the broadest sense is anything that can be the subject of a first‐order predication. Examples are individuals (such as my cat Trinidad), pluralities (such as my cats Trinidad, Seneca, and Seymour), masses (such as some cat food), and kinds (such as the cat breed korat). Here I'm including entities in this broadest sense because my thesis that descriptions are predicates applies to all sorts of descriptions: singular descriptions (‘the cat’), plural definite descriptions (‘the cats’), mass descriptions (‘the cat food’), kind descriptions (‘the korat’), and indefinite descriptions as well.
Preterm labor and preterm premature rupture of membranes have a different pattern in the involved compartments of acute histologoic chorioamnionitis and/or funisitis: Patho‐physiologic implication related to different clinical manifestations
Authors: Park Chan‐Wook , Park Joong Shin , Moon Kyung Chul , Jun Jong Kwan , Yoon Bo Hyun
Published: April 2016

It is unknown whether histo‐topographic findings about the involved compartments (i.e., choriodecidua, amnion, chorionic‐plate) of acute‐histologic chorioamnionitis (acute‐HCA) and/or funisitis according to the presence or absence of intra‐amniotic inflammation (IAI) and/or fetal inflammatory response syndrome (FIRS) are different between preterm labor and intact membranes (PTL) and preterm premature rupture of membranes (preterm‐PROM). The involved compartments of acute‐HCA and/or funisitis were examined in 161 singleton preterm‐births (<34 weeks) due to PTL (n = 88) and preterm‐PROM (n = 73). The study‐population was divided into IAI(−)/FIRS(−), IAI(+)/FIRS(−), and IAI(+)/FIRS(+) groups according to the presence or absence of IAI (amniotic‐fluid MMP‐8 ≥ 23 ng/ml) and/or FIRS (umbilical‐cord plasma CRP ≥ 200 ng/ml). Histological inflammation was not detected in any‐compartment except choriodecidua in IAI(−)/FIRS(−) group with PTL while inflammation appeared in all‐compartment0s (choriodeciduitis‐46.2 %; amnionitis‐23.1 %; funisitis‐30.8 %; chorionic‐plate inflammation‐7.7 %) in IAI(−)/FIRS(−) group with preterm‐PROM. IAI(+)/FIRS(−) group had a significantly higher frequency of inflammation in each‐compartment than IAI(−)/FIRS(−) group in PTL (each‐for P < 0.01), but not preterm‐PROM (each‐for P > 0.1). However, IAI(+)/FIRS(+) group had a significantly higher rate of inflammation in each compartment than IAI(+)/FIRS(−) group in both PTL and preterm‐PROM (each‐for P < 0.05). We first demonstrated that PTL and preterm‐PROM had a different pattern in the involved compartments of acute‐HCA and/or funisitis in the IAI(−)/FIRS(−‐) group and in the change of involved compartments from IAI(−)/FIRS(−) to IAI(+)/FIRS(−)
Possible origin of ratoon stunting disease following interspecific hybridization of Saccharum species
Authors: Young A. J.
Published: April 2016

Ratoon stunting disease (RSD) is the most economically significant disease of sugarcane, and, although it was first discovered in 1945, surprisingly little is understood of the nature of the relationship between the host and the pathogen, Leifsonia xyli subsp. xyli. This review traces RSD to the release of modern commercial hybrids, and provides evidence that Saccharum officinarum, the major progenitor of modern sugarcane cultivars, is not the natural host for L. xyli subsp. xyli. Rather, it is proposed that the wild relative, S. spontaneum, is more likely to be the original host, and that L. xyli subsp. xyli was acquired during interspecific hybridization work undertaken in Java during the 1920s. The release of the universally adopted variety POJ2878 then facilitated the dissemination of a single, worldwide clone of L. xyli subsp. xyli. The implications of the hypothesis are discussed in relation to plant improvement and the potential for new diseases to emerge through further attempts at broadening the genetic base of commercial sugarcane.
A Path‐Based Method for Simulating Large Deviations and Rare Events in Nonlinear Lightwave Systems
Authors: Li J. , Kath W. L.
Published: April 2016

Errors in nonlinear lightwave systems are often associated with rare, noise‐induced, large deviations of the signal. We present a method to determine the most probable manner in which such rare events occur by solving a sequence of constrained optimization problems. These results then guide importance‐sampled Monte Carlo simulations to determine the events' probabilities. The method applies to a general class of intensity‐based optical detectors and to arbitrarily shaped and multiple pulses.
Mortality risk and associated factors in HIV‐exposed, uninfected children
Authors: Arikawa Shino , Rollins Nigel , Newell Marie‐Louise , Becquet Renaud
Published: April 2016

Objective

With increasing maternal antiretroviral treatment (ART), the number of children newly infected with HIV has declined. However, the possible increased mortality in the large number of HIV‐exposed, uninfected (HEU) children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors.

Methods

Systematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HIV‐unexposed, uninfected (HUU) children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random‐effects models were fitted to obtain pooled estimates.

Results

A total of 14 studies were included in the meta‐analysis and 13 in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0–7.2; I2 = 94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6–15.0; I2 = 93%) at 24 months (four studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9–3.8; I2 = 93%) at 12 months (four studies) and 2.4 (95% CI: 1.1–5.1; I2 = 93%) at 24 months (three studies).

Conclusion

Compared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to characterise the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.