bluuebunny/crossref_metadata_2025 huggingface dataset:
The Severity of Hypoxic-Ischemic Encephalopathy Correlates With Multiple Organ Dysfunction in the Hypothermia Era
Authors: Alsina Miguel , Martín-Ancel Ana , Alarcon-Allen Ana , Arca Gemma , Gayá Francisco , García-Alix Alfredo
Published: January 2017

Objectives:

The objectives are to 1) determine whether there is a positive correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction and 2) evaluate the organ dysfunction pattern in infants with hypoxic-ischemic encephalopathy in the hypothermia era.

Design:

Retrospective observational study of prospective data collected between April 2009 and December 2012.

Setting:

The study took place in the neonatal ICU of Hospital Sant Joan de Déu–Hospital Clínic of Barcelona.

Patients:

Prospective consecutive newborns with greater than or equal to 36 weeks of gestation, greater than or equal to 1,800 g of weight at birth, and a diagnosis of hypoxic-ischemic encephalopathy was included.

Interventions:

Severity of hypoxic-ischemic encephalopathy was established before starting controlled hypothermia. Six organ systems and 23 clinical and laboratory variables were studied by means of an asymmetrical grading scale. Data were recorded daily during the first 72 hours of life.

Measurements and Main Results:

Seventy-nine patients were studied. All presented with multiple organ dysfunction on day 1. There were differences in the number of affected organs on day 1 according to hypoxic-ischemic encephalopathy stage (p < 0.001). Scale scores correlated positively with the severity of hypoxic-ischemic encephalopathy (area under the curve ranged from 0.77 to 0.87 on every day studied). There were significant differences in the severity of dysfunction of each organ system among the three hypoxic-ischemic encephalopathy stages (p < 0.05). Although the most frequently involved were hepatic and pH and electrolyte imbalance, the most severely affected were the respiratory and cardiovascular systems.

Conclusions:

In the hypothermia era, multiple organ dysfunction continues to be almost universal in newborns with hypoxic-ischemic encephalopathy. There is a high correlation between the severity of hypoxic-ischemic encephalopathy and multiple organ dysfunction during the first 3 days of life. A high index of suspicion of relevant multiple organ dysfunction is required in infants admitted with a diagnosis of severe hypoxic-ischemic encephalopathy. Patients with moderate hypoxic-ischemic encephalopathy present wide variability in the severity of multiple organ dysfunction. In the absence of multiple organ dysfunction, a perinatal hypoxic-ischemic origin of acute severe neonatal encephalopathy should be carefully reconsidered.
Androgen Receptor Expression in Endometrial Stromal Sarcoma: Correlation With Clinicopathologic Features
Authors: Roy Maitrayee , Kumar Sunesh , Bhatla Neerja , Ray Mukurdipi D. , Kumar Lalit , Jain Deepali , Phulware Ravi , Mathur Sandeep R.
Published: January 2017

Endometrial stromal sarcoma (ESS) is a rare neoplasm comprising only 0.2% to 1% of all uterine malignancies and occurs in women between 42 and 59 yr of age. ESSs frequently express estrogen receptor (ER) and progesterone receptor (PR). However, the published literature contains scant data on the expression and therapeutic/prognostic role of androgen receptor (AR) in ESSs. We undertook this study to characterize the expression of AR along with ER and PR in ESSs and correlate it with clinicopathologic features. The clinical details, slides, and blocks of 25 tumors from 24 patients (September 2010 to February 2016) were retrieved. The diagnosis and grade of ESS were reviewed and immunohistochemistry performed with anti-ER, PR, and AR antibodies. Ages ranged from 18 to 50 yr, with a mean age of 36 yr. Low-grade ESS (LGESS) and high-grade ESS (HGESS) were diagnosed in 15 and 9 patients, respectively. An 18-yr-old woman who initially had LGESS suffered a pelvic recurrence; that exhibited high-grade morphology. Our patients, especially those with HGESS, were much younger compared with published worldwide data. ER, PR, and AR immunoreactivity was observed in 14 (93.3%), 12 (80%), and 11 (73.3%) LGESSs, respectively. This is in contrast to HGESSs, in which 5 (50%) tumors had a triple-negative hormonal profile. AR, like ER and PR, was more frequently expressed in LGESS as compared with HGESS. Whether AR, in addition to ER and PR receptor status, may help guide adjuvant hormonal therapy needs further elucidation.
CD8, FoxP3, and CD45RO+ Lymphocytic Infiltrates in Type I and Type II Endometrial Cancers in African American and European American Females
Authors: Rashid Tariq , Young-Pierce Jennifer L. , Garrett-Mayer Elizabeth , Graybill Whitney , Neal Shelby , Spruill Laura S.
Published: January 2017

African American (AA) females with endometrial carcinoma have a significantly worse prognosis with regard to disease-free survival and overall survival than their European American (EA) counterparts and this finding is true across all stages and grades. The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated to be of prognostic significance in a variety of malignancies, including endometrial cancers. This study aims to determine whether clinically significant differences in levels of CD8+ cytotoxic T lymphocytes, FoxP3+ regulatory T lymphocytes, and CD45RO+ memory T lymphocytes exist between races and to document the clinical impact of TILs. One hundred ten patients with endometrial adenocarcinoma, treated with hysterectomy from 2003 to 2011 were studied. Patients were selected to provide equal representation across type and grade for both EAs and AAs. Immunohistochemical stains were used to highlight CD8-positive, FoxP3-positive, and CD45RO-positive TILs at the endometrial-myometrial interface on slides from paraffin-embedded tissue. Patients with “high” or “low” levels of TILs were compared with respect to the race, tumor type, and survival. High levels of CD45RO+ TILs were associated with improved overall survival in EA women (hazard ratio, 0.32; 95% confidence interval, 0.11-0.92; P=0.034). Comparatively, AA women with high levels of CD45RO+ TILs received no survival benefit (hazard ratio, 0.96; 95% confidence interval, 0.35-2.64; P=0.94). High levels of CD8-positive or FoxP3-positive TILs, alone, had no impact on survival. EA patients with TILs containing high levels of CD45RO cells but low levels of CD8+ cells lost the survival benefit; however, limited numbers preclude significant conclusions from this observation. Neither tumor type nor race were predictive of the levels of TILs of any type. Further study with a larger sample size is required to determine the impact of TIL subtype combinations on survival.
Frequent Mismatch Repair Protein Deficiency in Mixed Endometrioid and Clear Cell Carcinoma of the Endometrium
Authors: Köbel Martin , Tessier-Cloutier Basile , Leo Joyce , Hoang Lien N. , Gilks C. Blake , Soslow Robert A. , Delair Deborah , Stewart Colin J.R. , Lee Cheng-Han
Published: January 2017

Mixed endometrioid and clear cell carcinoma of the endometrium refers to a scenario in which the tumor exhibits histologic features of both endometrioid and clear cell carcinoma. We observed a tendency for these tumors to occur in a mismatch repair (MMR) protein-deficient molecular background in a prior study that examined a small cohort of mixed-type endometrial carcinomas. The aim of this study was to determine the rate of MMR protein deficiency in a larger series of endometrial mixed endometrioid and clear cell carcinomas, through a retrospective survey of MLH1, PMS2, MSH2, and MSH6 expression in such tumors at 5 tertiary centers. A total of 41 cases were identified and 27 (66%) tumors demonstrated MMR protein deficiency with a comparable frequency across the contributing centers (ranging from 56% to 83%). Among the MMR protein-deficient cases, 59% showed concurrent MLH1 and PMS2 loss, 33% showed concurrent MSH2 and MSH6 loss, and 4% showed isolated PMS2 or MSH6 loss. Compared with a previously published series of 15 pure endometrial clear cell carcinomas, mixed endometrioid and clear cell carcinomas are associated with significantly better disease-specific survival (P=0.02). In summary, endometrial carcinomas with mixed endometrioid and clear cell histology are frequently MMR protein deficient. This finding has implications both for our understanding of its tumor biology and for the identification of patients with potential Lynch syndrome.
Pediatric HIV Disclosure Intervention Improves Knowledge and Clinical Outcomes in HIV-Infected Children in Namibia
Authors: Beima-Sofie Kristin M. , Brandt Laura , Hamunime Ndapewa , Shepard Mark , Uusiku James , John-Stewart Grace C. , O'Malley Gabrielle
Published: January 2017

Objectives:

Using routinely collected data, we evaluated a nationally implemented intervention to assist health care workers and caregivers with HIV disclosure to children. We assessed the impact of the intervention on child's knowledge and health outcomes.

Methods:

Data were abstracted from national databases and patient charts for HIV-infected children aged 7–15 years attending 4 high-volume HIV clinics in Namibia. Disclosure rates, time to disclosure, and HIV knowledge in 314 children participating in the intervention were analyzed. Logistic regression was used to identify correlates of partial vs. full disclosure. Paired t-tests and McNemar tests were used to compare adherence and viral load (VL) before versus after intervention enrollment.

Results:

Among children who participated in the disclosure intervention, 11% knew their HIV status at enrollment and an additional 38% reached full disclosure after enrollment. The average time to full disclosure was 2.5 years (interquartile range: 1.2–3 years). Children who achieved full disclosure were more likely to be older, have lower VLs, and have been enrolled in the intervention longer. Among children who reported incorrect knowledge regarding why they take their medicine, 83% showed improved knowledge after the intervention, defined as knowledge of HIV status or adopting intervention-specific language. On comparing 0–12 months before vs. 12–24 months after enrollment in the intervention, VL decreased by 0.5 log10 copies per milliliter (N = 42, P = 0.004), whereas mean adherence scores increased by 10% (N = 88, P value < 0.001).

Conclusions:

This HIV disclosure intervention demonstrated improved viral suppression, adherence, and HIV knowledge and should be considered for translation to other settings.
Nevirapine Pharmacokinetics and Safety in Neonates Receiving Combination Antiretroviral Therapy for Prevention of Vertical HIV Transmission
Authors: Lau Elaine , Brophy Jason , Samson Lindy , Kakkar Fatima , Campbell Douglas M. , Yudin Mark H. , Murphy Kellie , Seto Winnie , Colantonio David , Read Stanley E. , Bitnun Ari
Published: January 2017

Background:

Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics and safety of this regimen.

Methods:

Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m2 daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 [target trough (NVP-T): 3–8 mg/L].

Results:

Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32–41 weeks) and 2.9 kg (1.5–4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6–25.1 mg/L), 3.5 mg/L (1.6–6.8 mg/L), and 4.3 mg/L (0.1–19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L·kg−1·h−1 (0.01–0.50 L·kg−1·h−1) at week 2 to 0.18 L·kg−1·h−1 (0.01–0.78 L·kg−1·h−1) at week 4. Increased drug exposure [area under the curve (AUCτ)] correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%).

Conclusions:

Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA.
Outcomes following electrographic seizures and electrographic status epilepticus in the pediatric and neonatal ICUs
Authors: Pinchefsky Elana F. , Hahn Cecil D.
Published: January 2017

Purpose of review

Increasing recognition of electrographic seizures and electrographic status epilepticus in critically ill neonates and children has highlighted the importance of identifying their potential contributions to neurological outcomes to guide optimal management.

Recent findings

Recent studies in children and neonates have found an independent association between increasing seizure burden and worse short-term and long-term outcomes, even after adjusting for other important contributors to outcome such as seizure cause and illness severity. The risk of worse neurological outcome has been shown to increase above a seizure burden threshold of 12–13 min/h, which is considerably lower than the conventional definition of status epilepticus of 30 min/h. Randomized controlled trials in neonates have demonstrated that electroencephalography-targeted therapy can successfully reduce seizure burden, but due to their small size these trials have not been able to demonstrate that more aggressive electroencephalography-targeted treatment of both subclinical and clinical seizures results in improved outcome.

Despite mounting evidence for an independent association between increasing seizure burden and worse outcome, further study is needed to determine whether early seizure identification and aggressive antiseizure treatment can improve neurodevelopmental outcomes.
Cognition in epilepsy: current clinical issues of interest
Authors: Witt Juri-Alexander , Helmstaedter Christoph
Published: January 2017

Purpose of review

This review provides an update and summary of recent neuropsychological findings in epilepsy focusing on three major clinical topics among the many developments in the field. We will critically outline the current state with regard to cognition in new-onset epilepsies, social cognition in epilepsy, and the long-term outcome of epilepsy surgery and the cognitive outcomes of superselective surgical procedures.

Recent findings

Current studies indicate that neuropsychological impairments are prevalent already at the onset of epilepsy and even before, social cognition (i.e., emotion recognition and theory of mind) is impaired in different epilepsy populations, the long-term outcome of epilepsy surgery is mostly characterized by a stable or even improved cognitive status, and superselective epilepsy surgeries are associated with a promising neuropsychological outcome.

The high prevalence of cognitive deficits around epilepsy onset challenges the assumption that epilepsy is the major cause of cognitive problems and calls for early neuropsychological diagnostics. Social cognition seems to be a relevant domain that is not yet routinely considered in epilepsy. The cognitive long-term outcome of epilepsy surgery is mostly positive. Stereotactic thermocoagulation and gamma knife surgery appear to be cognitively safe procedures.
Dominant integration locus drives continuous diversification of plant immune receptors with exogenous domain fusions
Authors: Bailey Paul C. , Schudoma Christian , Jackson William , Baggs Erin , Dagdas Gulay , Haerty Wilfried , Moscou Matthew , Krasileva Ksenia V.
Published: January 2017

Background

The plant immune system is innate, encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes.

Results

We showed that plant immune receptors with integrated domains are distributed unevenly across their phylogeny in grasses. Using phylogenetic analysis, we uncovered a major integration clade, whose members underwent repeated independent integration events producing diverse fusions. This clade is ancestral in grasses with members often found on syntenic chromosomes. Analyses of these fusion events revealed that homologous receptors can be fused to diverse domains. Furthermore, we discovered a 43 amino acids long motif that was associated with this dominant integration clade and was located immediately upstream of the fusion site. Sequence analysis revealed that DNA transposition and/or ectopic recombination are the most likely mechanisms of NLR-ID formation.

Conclusions

The identification of this subclass of plant immune receptors that is naturally adapted to new domain integration will inform biotechnological approaches for generating synthetic receptors with novel pathogen ‘baits’.
The effect of dietary ginseng polysaccharide supplementation on the immune responses involved in porcine milk-derived esRNAs
Authors: Sun Jiajie , Yao Liyuan , Chen Ting , Xi Qianyun , Zhang Yongliang
Published: January 2017

Ginseng and its polysaccharides (GPS) have been well known as an immune modulator. This study was conducted to investigate the effects of dietary supplemental GPS on the immune responses involved in sow’s milk-derived exosomal shuttle RNAs (esRNAs) using RNA-Seq and miRNA-Seq. Of the 213 identified miRNA types, a total of 26 conserved miRNAs were differently expressed in response to GPS supplementation, including 10 up-regulated and 16 down-regulated miRNAs in GPS feeding group. In addition, exosomal transcriptome analysis identified 14,696 protein-coding genes in sow’s milk exosomes, and 283 genes with 204 and 79 candidates showing up and down-regulation were significantly responded to GPS supplementation. Integrated analysis of each differently expressed miRNA with significantly expressed genes further revealed the presence of 51 highly conserved miRNA-gene interactions that were annotated to be related to immunoregulatory functions. This work provided an important advance in the functional identification of dietary GPS supplementation and more fundamental information about how GPS promoted the immune response and healthy growth of the infant from mothers at molecular levels.
Reduced foraging investment as an adaptation to patchy food sources: a phasic army ant simulation
Authors: Teseo Serafino , Delloro Francesco
Published: January 2017

Colonies of several ant species within the subfamily Dorylinae alternate stereotypical discrete phases of foraging and reproduction. Such phasic cycles are thought to be adaptive because they minimize the amount of foraging and the related costs, and at the same time enhance the colony-level ability to rely on patchily distributed food sources. In order to investigate these hypotheses, we use here a simple computational approach to study the population dynamics of two species of virtual ant colonies that differ quantitatively in their foraging investment. One species, which we refer to as “phasic”, forages only half of the time, mirroring the phasic activity of some army ants; the other “non-phasic” species forages instead all the time. We show that, when foraging costs are relatively high, populations of phasic colonies grow on average faster than non-phasic populations, outcompeting them in mixed populations. Interestingly, such tendency becomes more consistent as food becomes more difficult to find but locally abundant. According to our results, reducing the foraging investment, for example by adopting a phasic lifestyle, can result in a reproductive advantage, but only in specific conditions. We thus suggest phasic colony cycles to have emerged together with the doryline specialization in feeding on the brood of other eusocial insects, a resource that is hard to obtain but highly abundant if available.
Symptoms of Depression in a Large Healthy Population Cohort are related to Subjective Memory Complaints and Memory Performance in Negative Contexts
Authors: Schweizer Susanne , Kievit Rogier A. , Emery Tina ,   Cam-CAN, Henson Richard N.
Published: January 2017

Decades of research have investigated the impact of clinical depression on memory, which has revealed biases and in some cases impairments. However, little is understood about the effects of sub-clinical symptoms of depression on memory performance in the general population. Here we report the effects of symptoms of depression on memory problems in a large population-derived cohort (N = 2544), 87% of whom reported at least one symptom of depression. Specifically, we investigate the impact of depressive symptoms on subjective memory complaints, objective memory performance on a standard neuropsychological task and, in a subsample (n = 288), objective memory in affective contexts. There was a dissociation between subjective and objective memory performance, with depressive symptoms showing a robust relationship with self-reports of memory complaints, even after adjusting for age, gender, general cognitive ability and symptoms of anxiety, but not with performance on the standardised measure of verbal memory. Contrary to our expectations, hippocampal volume (assessed in a subsample, n = 592) did not account for significant variance in subjective memory, objective memory or depressive symptoms. Nonetheless, depressive symptoms were related to poorer memory for pictures presented in negative contexts, even after adjusting for memory for pictures in neutral contexts. Thus the symptoms of depression, associated with subjective memory complaints, appear better assessed by memory performance in affective contexts, rather than standardised memory measures. We discuss the implications of these findings for understanding the impact of depressive symptoms on memory functioning in the general population.
asymptoticMK: A web-based tool for the asymptotic McDonald–Kreitman test
Authors: Haller Benjamin C. , Messer Philipp W.
Published: January 2017

The McDonald–Kreitman (MK) test is a widely used method for quantifying the role of positive selection in molecular evolution. One key shortcoming of this test lies in its sensitivity to the presence of slightly deleterious mutations, which can severely bias its estimates. An asymptotic version of the MK test was recently introduced that addresses this problem by evaluating polymorphism levels for different mutation frequencies separately, and then extrapolating a function fitted to that data. Here we present asymptoticMK, a web-based implementation of this asymptotic McDonald–Kreitman test. Our web service provides a simple R-based interface into which the user can upload the required data (polymorphism and divergence data for the genomic test region and a neutrally evolving reference region). The web service then analyzes the data and provides plots of the test results. This service is free to use, open-source, and available athttp://benhaller.com/messerlab/asymptoticMK.html.
Rapidde novoassembly of the European eel genome from nanopore sequencing reads
Authors: Jansen Hans J. , Liem Michael , Jong-Raadsen Susanne A. , Dufour Sylvie , Weltzien Finn-Arne , Swinkels William , Koelewijn Alex , Palstra Arjan P. , Pelster Bernd , Spaink Herman P. , van den Thillart Guido E. , Dirks Ron P. , Henkel Christiaan V.
Published: January 2017

We have sequenced the genome of the endangered European eel using the MinION by Oxford Nanopore, and assembled these data using a novel algorithm specifically designed for large eukaryotic genomes. For this 860 Mbp genome, the entire computational process takes two days on a single CPU. The resulting genome assembly significantly improves on a previous draft based on short reads only, both in terms of contiguity (N50 1.2 Mbp) and structural quality. This combination of affordable nanopore sequencing and light-weight assembly promises to make high-quality genomic resources accessible for many non-model plants and animals.
DNA-dependent RNA cleavage by the Natronobacterium gregoryi Argonaute
Authors: Ye Sunghyeok , Bae Taegeun , Kim Kyoungmi , Habib Omer , Lee Seung Hwan , Kim Yoon Young , Lee Kang-In , Kim Seokjoong , Kim Jin-Soo
Published: January 2017

We show here that, unlike most other prokaryotic Argonaute (Ago) proteins, which are DNA-guided endonucleases, the Natronobacterium gregoryi-derived Ago (NgAgo) can function as a DNA-guided endoribonuclease, cleaving RNA, rather than DNA, in a targeted manner. The NgAgo protein, in complex with 5’-hydroxylated or 5’-phosphrylated oligodeoxyribonucleotides (ODNs) of variable lengths, split RNA targets into two or more fragments in vitro, suggesting its physiological role in bacteria and demonstrating a potential for degrading RNA molecules such as mRNA or lncRNA in eukaryotic cells in a targeted manner.
Lacking conservation genomics in the giant Galápagos tortoise
Authors: Loire Etienne , Galtier Nicolas
Published: January 2017

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100031).

Conservation policy in the giant Galápagos tortoise, an iconic endangered animal, has been assisted by genetic markers for ∼15 years: a dozen loci have been used to delineate thirteen (sub)species, between which hybridization is prevented. Here, comparative reanalysis of a previously published NGS data set reveals a conflict with traditional markers. Genetic diversity and population substructure in the giant Galápagos tortoise are found to be particularly low, questioning the genetic relevance of current conservation practices. Further examination of giant Galapagos tortoise population genomics is critically needed.
The human initiator is a distinct and abundant element that is precisely positioned in focused core promoters
Authors: Vo ngoc Long , Cassidy California Jack , Huang Cassidy Yunjing , Duttke Sascha H.C. , Kadonaga James T.
Published: January 2017

DNA sequence signals in the core promoter, such as the initiator (Inr), direct transcription initiation by RNA polymerase II. Here we show that the human Inr has the consensus of BBCA+1BW at focused promoters in which transcription initiates at a single site or a narrow cluster of sites. The analysis of 7678 focused transcription start sites revealed 40% with a perfect match to the Inr and 16% with a single mismatch outside of the CA+1 core. TATA-like sequences are underrepresented in Inr promoters. This consensus is a key component of the DNA sequence rules that specify transcription initiation in humans.
Production of the antibiotic secondary metabolite solanapyrone A by the fungal plant pathogen Ascochyta rabiei during fruiting body formation in saprobic growth
Authors: Kim Wonyong , Park Jeong‐Jin , Dugan Frank M. , Peever Tobin L. , Gang David R. , Vandemark George , Chen Weidong
Published: January 2017

Fungi are noted producers of a diverse array of secondary metabolites, many of which are of pharmacological importance. However, the biological roles of the vast majority of these molecules during the fungal life cycle in nature remain elusive. Solanapyrones are polyketide‐derived secondary metabolites produced by diverse fungal species including the plant pathogen Ascochyta rabiei. This molecule was originally thought to function as a phytotoxin facilitating pathogenesis of A. rabiei. Chemical profiling and gene expression studies showed that solanapyrone A was specifically produced during saprobic, but not parasitic growth of A. rabiei. Expression of the gene encoding the final enzymatic step in solanapyrone biosynthesis was specifically associated with development of the asexual fruiting bodies of the fungus on certain substrates. In confrontation assays with saprobic fungi that were commonly found in chickpea debris in fields, A. rabiei effectively suppressed the growth of all competing fungi, such as Alternaria, Epicoccum and Ulocladium species. Solanapyrone A was directly detected in the inhibitory zone using a MALDI‐imaging mass spectrometry, and the purified compound showed significant antifungal activities against the potential saprobic competitors. These results suggest that solanapyrone A plays an important role for competition and presumably the survival of the fungus.
Endemic cyanophages and the puzzle of phage‐bacteria coevolution
Authors: Cordero Otto X.
Published: January 2017

A recent genomic analysis of Synechococcus cyanophages sampled for over 15 years reveals a remarkable pattern of stable phage population structure, highly reminiscent of the ecotype structure observed in bacteria and archaeal ecotypes. In this highlight I discuss the importance of this finding and the questions and opportunities it opens to learn more about the nature of phage‐bacterial coevolution in the environment.
‘When words don't come easily’: personal narratives from adolescents experiencing shyness as an emotional and behavioural problem in the school context
Authors: Lund Ingrid
Published: January 2017

The purpose of this article is to present narratives from 15 adolescents experiencing shy behaviour as an emotional and behavioural problem in the school context in light of narrative understanding. The investigation is intended to generate knowledge about this largely under‐researched phenomenon based on the personal accounts of those who are actually experiencing it. Their narratives are the foundation for a discussion regarding implications for future practice in the context of school in relation to this group.
Redefining disability in the context of ‘masyarakat madani’, an Indonesian model of inclusive society
Authors: Agustian Hendra Y.
Published: January 2017

The Indonesian model of inclusive society ‘masyarakat madani’ is arguably based on a one‐view perspective of Islamic intellectuals. Although it was intended to embrace the whole of society in general, its implications might not reach and permeate the entire society. The unique features of Indonesian society have, to a certain degree, made the understanding of inclusive society rather complicated and ambiguous. Nevertheless, the aspiration of creating a more inclusive Indonesian society will perpetually be heralded as one way of tackling the multidimensional challenges faced by Indonesia.
Designed by the pupils, for the pupils: an autism‐friendly school
Authors: McAllister Keith , Sloan Sean
Published: January 2017

There is growing interest in promoting autism‐friendly environments, especially in a school setting. Findings to date have generally advocated an accepted reductionist or generalist approach when providing an autism‐friendly built environment. However, previous studies, while very well intentioned, have rarely involved those with autism spectrum condition (ASC) to comment on and then instruct designers on what, for them, constitutes an autism‐friendly learning environment. If going to be truly inclusive, the authors contend that those who are most knowledgeable about ASC, those with ASC, should, whenever possible, be given the opportunity to comment on the design of our shared built environment. Hence this article first introduces some of the challenges faced by those with ASC in trying to cope with their surroundings, before proceeding to outline the development of a simple school design ‘jigsaw’ kit that helped pupils with ASC to communicate ideas for their perfect school. Used in four design workshops, secondary school aged pupils (aged 13 to 18) with ASC imparted their likes, dislikes and what was most important to them within the school environment. This facilitated comparison with current autism‐friendly guidelines and provides a valuable insight into the mind of the secondary pupil with ASC. It is hoped that by increasing awareness and then including those with ASC in describing what might constitute an autism‐friendly learning environment, it will help facilitate greater inclusion of the child with ASC into mainstream education and society at large.
Misoprostol for cervical priming prior to hysteroscopy in postmenopausal and premenopausal nulliparous women; a multicentre randomised placebo controlled trial
Authors: Tasma ML , Louwerse MD , Hehenkamp WJ , Geomini PM , Bongers MY , Veersema S , van Kesteren PJ , Tromp E , Huirne JA , Graziosi GC
Published: January 2017

Objective

To evaluate the reduction of pain by misoprostol compared with placebo prior to hysteroscopy in postmenopausal and premenopausal nulliparous women.

Design

Randomised multicentre double‐blind placebo controlled trial.

Setting

Two Dutch teaching hospitals and one Dutch university medical centre.

Population

Postmenopausal and premenopausal nulliparous women undergoing office hysteroscopy.

Methods

Patients were randomised to receive either 400 microgram misoprostol or placebo 12 and 24 hours before hysteroscopy. Pain was quantified by the use of real time pain measurement using the continuous pain score meter (CPSM) and VAS scores.

Main outcome measures

Primary outcome was pain measured by the CPSM during passage of the hysteroscope through the cervical canal, quantified by the area under the curve (AUC). Secondary outcomes included VAS scores, other CPSM parameters, failures and side effects.

Results

In all, 149 patients were randomly assigned to either misoprostol (n = 74) or placebo (n = 75). The AUC during introduction did not significantly differ between the intervention and the placebo group. The VAS score during introduction, however, demonstrated a significant difference in premenopausal nulliparous women favouring misoprostol: 2.9 (95% CI 1.3–4.4) versus placebo 5.5 (95% CI 3.9–7.1), P = 0.02, as well as the AUC during the entire procedure: 618 (95% CI 410–827) versus 1126 (95% CI 671–1580), P = 0.04. Failures were equally distributed between the misoprostol (16%) and placebo group (13%). Intestinal side effects occurred significantly more frequently in the misoprostol group (67%) than in the placebo group (32%) [OR 4.2 (95% CI 2.1–8.3), P < 0.01].

Conclusion

Misoprostol prior to hysteroscopy reduces pain in premenopausal nulliparous women but not in postmenopausal women. It does cause side effects.

Tweetable abstract

RCT: misoprostol versus placebo prior to hysteroscopy in 149 women significantly reduces some pain parameters.
The Impact of a Soiled Airway on Intubation Success in the Emergency Department When Using the GlideScope or the Direct Laryngoscope
Authors: Sakles John C. , Corn G. Judson , Hollinger Patrick , Arcaris Brittany , Patanwala Asad E. , Mosier Jarrod M.
Published: January 2017

Background

The objective was to determine the impact of a soiled airway on firstpass success when using the GlideScope video laryngoscope or the direct laryngoscope for intubation in the emergency department (ED).

Methods

Data were prospectively collected on all patients intubated in an academic ED from July 1, 2007, to June 30, 2016. Patients ≥ 18 years of age, who underwent rapid sequence intubation by an emergency medicine resident with the GlideScope or the direct laryngoscope, were included in the analysis. Data were stratified by device used (GlideScope or direct laryngoscope). The primary outcome was firstpass success. Patients were categorized as those without blood or vomitus (CLEAN) and those with blood or vomitus (SOILED) in their airway. Multivariate regression models were developed to control for confounders.

Results

When using the GlideScope, the firstpass success was lower in the SOILED group (249/306; 81.4%) than the in CLEAN group (586/644, 91.0%; difference = 9.6%; 95% confidence interval [CI] = 4.7%–14.5%). Similarly, when using the direct laryngoscope, the firstpass success was lower in the SOILED group (186/284, 65.5%) than in the CLEAN group (569/751, 75.8%; difference = 10.3%; 95% CI = 4.0%–16.6%). The SOILED airway was associated with a decreased firstpass success in both the GlideScope cohort (adjusted odds ratio [aOR] = 0.4; 95% CI = 0.3–0.7) and the direct laryngoscope cohort (aOR = 0.6; 95% CI = 0.5–0.8).

Conclusion

Soiling of the airway was associated with a reduced firstpass success during emergency intubation, and this reduction occurred to a similar degree whether using either the GlideScope or the direct laryngoscope.
The Australian Census Longitudinal Dataset: using record linkage to create a longitudinal sample from a series of cross‐sections
Authors: Chipperfield James , Brown James J. , Watson Nicole
Published: January 2017

The Australian Bureau of Statistics is creating a longitudinal sample, called the Australian Census Longitudinal Dataset (ACLD), by linking person records across its five‐yearly Census of Population and Housing. This paper proposes a Multi‐Panel framework for selecting and weighting records in the ACLD. This framework can be applied more generally to selecting longitudinal samples from a series of cross‐sectional administrative files. The proposed framework avoids some significant limitations of the popular ‘Top‐Up’ sampling approach to maintaining the cross‐sectional and longitudinal representativeness of a sample over time.
Amplitude‐integrated electroencephalography can predict neurodevelopmental outcome at 12 months of corrected age in very preterm infants
Authors: Ralser Elisabeth , Neubauer Vera , Pupp‐Peglow Ulrike , Kiechl‐Kohlendorfer Ursula , Griesmaier Elke
Published: January 2017

Aim

It is difficult to find diagnostic tools than can reliably predict neurodevelopmental outcomes in very preterm infants in clinical practice. This study evaluated whether amplitude‐integrated electroencephalography predicted neurodevelopmental outcome in preterm infants when they reached 12 months of corrected age.

Methods

Between October 2007 and December 2013, we studied 232 preterm infants (51% male) at Innsbruck Medical University Hospital, Austria. Their mean birthweight was 1264 g, and their mean gestational age was 29.5 weeks. Amplitude‐integrated electroencephalography was evaluated using the Burdjalov score, and outcomes were assessed using the Bayley Scales of Infant Development – Second Edition.

Results

The cohort was divided into three subgroups: 154 infants with normal outcomes, 53 infants with moderate delays and 25 infants with severe delays. The amplitude‐integrated electroencephalography Burdjalov scores were lower in infants with moderate delays than in infants with normal outcomes and even lower in infants with severe delays. The highest area under the curve (0.776) for the Burdjalov score was at 18–24 hours of life.

Conclusion

Our study confirmed the predictive value of amplitude‐integrated electroencephalography and showed that this needed to be carried out early in life to provide reliable information on neurodevelopmental outcomes in very preterm infants.
Comparative cardiovascular risks of dipeptidyl peptidase 4 inhibitors with other second‐ and third‐line antidiabetic drugs in patients with type 2 diabetes
Authors: Ou Huang‐Tz , Chang Kai‐Cheng , Li Chung‐Yi , Wu Jin‐Shang
Published: January 2017

Aims

Dipeptidyl peptidase 4 inhibitors (DPP4is) are suggested as a second‐ and third‐line antidiabetic treatment for type 2 diabetes. Previous studies assessed only the cardiovascular effects of DPP4is as a second‐line treatment, included sulphonylurea as the only comparator, and yielded inconclusive results on the risk of heart failure. The present study therefore evaluated the comparative cardiovascular risks of DPP4is with other second‐ and third‐line antidiabetic drugs.

Methods

Based on a large nationwide diabetic cohort, 113 051 patients with type 2 diabetes newly on metformin‐based dual or triple therapy were identified in 2009–2011 and followed until 2013, or death if this occurred sooner. Primary interest targeted hospitalizations for ischaemic stroke, myocardial infarction and heart failure. Secondary outcomes were hypoglycaemia and all‐cause mortality. Cox proportional hazards models were performed to assess time‐to‐event hazard ratio between propensity score‐matched antidiabetic treatment groups.

Results

DPP4is as a second‐line add‐on to metformin had a significantly lower stroke risk [hazard ratio (HR) 0.817 (95% confidence interval 0.687, 0.971)] and all‐cause mortality [HR 0.825 (0.687, 0.992)] than those for sulphonylurea. DPP4is as a third‐line add‐on to metformin and sulphonylurea combined dual therapy had a significantly lower risk for stroke [HR 0.826 (0.740, 0.923)] and all‐cause mortality [HR 0.784 (0.701, 0.878)] than those for acarbose, and significantly lower risks for stroke [HR 0.653 (0.542, 0.786)], heart failure [HR 0.721 (0.568, 0.917)] and all‐cause mortality [HR 0.689 (0.594, 0.703)] than those for meglitinide.

Conclusions

DPP4is as a second‐ or third‐line add‐on treatment provided cardiovascular benefits and posed no increased risks for heart failure, hypoglycaemia or death.
A novel dual amylin and calcitonin receptor agonist, KBP‐089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference
Authors: Gydesen Sofie , Hjuler Sara Toftegaard , Freving Zenia , Andreassen Kim Vietz , Sonne Nina , Hellgren Lars I , Karsdal Morten Asser , Henriksen Kim
Published: January 2017

Background and Purpose

Obesity and associated co‐morbidities, such as type 2 diabetes and non‐alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co‐morbidities.

Experimental Approach

The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP‐089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight‐independent effects of KBP‐089 using a weight‐matched group.

Key Results

Rats fed a high‐fat diet were treated, s.c., with KBP‐089 0.625, 1.25, 2.5 μg·kg−1 or vehicle. KB‐089 induced in a dose‐dependent and sustained weight loss (~17% by 2.5 μg·kg−1). Moreover, KBP‐089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP‐089 improved glucose homeostasis through improved insulin action. To obtain a weight‐matched group, significantly less food was offered (9% less than in the KBP‐089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP‐089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP‐089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle.

Conclusions and Implications

The novel DACRA, KBP‐089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet‐induced weight loss.
Predictive factors of the tumor immunological microenvironment for long‐term follow‐up in early stage breast cancer
Authors: Okabe Mina , Toh Uhi , Iwakuma Nobutaka , Saku Shuko , Akashi Momoko , Kimitsuki Yuko , Seki Naoko , Kawahara Akihiko , Ogo Etsuyo , Itoh Kyogo , Akagi Yoshito
Published: January 2017

The aim of this research was to investigate the correlation of immunologic factors in the tumor environment of breast cancer, using immunohistological staining to evaluate the expression of programmed death 1/programmed death ligand 1 (PD‐1/PD‐L1), phosphatase and tensin homolog (PTEN), tumor infiltrating lymphocytes (TILs), and macrophages, and to analyze the association between the immunologic factors and clinical outcome for patients with early stage breast cancer (EBC). A total of 97 EBC patients who underwent standard surgery were investigated. Expression of PD‐1/PD‐L1 and PTEN and the density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages were evaluated by immunohistochemical analysis. The association between the immunologic factors and clinical outcome was statistically analyzed. The density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages and non‐expression of PTEN was significantly higher in cases of triple negative breast cancer. CD8+ TIL density and CD8+/PD‐L1+ expression were predictive factors for disease‐free survival and overall survival (OS). Human epidermal growth factor 2 (HER2)‐positive patients with PTEN expression and luminal/HER2‐negative patients without PD‐L1 expression had significantly longer OS compared to patients without PTEN expression (P = 0.049) and with PD‐L1 expression (P = 0.036), respectively. Furthermore, patients with PD‐L1+/CD8+ expression had worse median progression‐free survival (P = 0.022) and median OS (P = 0.037) compared with patients without PD‐L1+/CD8+ expression. The CD3+ TILs, CD8+ TILs, and CD163+ macrophages were shown to infiltrate the tumor area of EBC. In particular, triple negative breast cancer had a higher rate of TIL infiltration within the tumor environment. Expression of PTEN and lack of PD‐L1 expression were associated with favorable survival in HER2‐positive and luminal/HER2‐negative EBC patients, respectively. The PD‐L1 expression combined with CD8+ density was significantly associated with an aggressive clinical outcome.
Regional difference in sulcal infolding progression correlated with cerebral cortical expansion in cynomolgus monkey fetuses
Authors: Sawada Kazuhiko , Fukunishi Katsuhiro , Kashima Masatoshi , Imai Noritaka , Saito Shigeyoshi , Aoki Ichio , Fukui Yoshihiro
Published: January 2017

The present study aimed to specify the cerebral sulci developed by cortical expansion in cynomolgus monkey fetuses. The degree of sulcal infolding was evaluated by the gyrification index (GI), which was quantified using ex vivo magnetic resonance imaging. The correlation of cortical volume with the sulcal GI was most frequent during embryonic days (EDs) 100 to 120. Interestingly, the high correlation was marked during EDs 140 to 150 in restricted primary sulci in prefrontal, parietotemporal and medial temporal regions. The present results suggest that cortical expansion is involved in gyral demarcation by sulcal infolding, followed by the sulcal infolding progression in phylogenetically‐newer cortices.
Cannabis use and dating violence among college students: A call for research
Authors: Shorey Ryan C. , Haynes Ellen , Strauss Catherine , Temple Jeff R. , Stuart Gregory L.
Published: January 2017

Dating violence is a serious and prevalent problem on college campuses. Although there is a robust literature documenting that alcohol use is consistently associated with increased risk for perpetrating dating violence, little research has examined the role of cannabis in dating violence perpetration. With increasing legalisation of cannabis throughout the world, it is imperative to understand what role, if any, cannabis may play in the important public health problem of dating violence. In this commentary, we discuss the current state of the research on cannabis and dating violence and suggest avenues for additional research in this area. It is critical that we conduct methodologically sound research on the association between cannabis and dating violence so that we can understand what role, if any, cannabis exerts on this important problem. [Shorey RC, Haynes E, Strauss C, Temple JR, Stuart GL. Cannabis use and dating violence among college students: A call for research. Drug Alcohol Rev 2017;36:17–19]