bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual variation in plasticity dulls transgenerational responses to stress
Authors: Gillis Michael K. , Walsh Matthew R.
Published: July 2019

Much research has shown that environmental stress can induce adaptive and maladaptive phenotypic changes in organisms that persist for multiple generations. Such transgenerational phenotypic plasticity shrouds our understanding of the long‐term consequences of ongoing anthropogenic pressures.

Here, we evaluated within‐ and transgenerational phenotypic responses to food stress in the freshwater crustacean, Daphnia. We reared 45 clones of Daphnia pulicaria each on high‐quality Scenedesmus and low‐quality (but also non‐toxic) cyanobacteria (generation 1). Offspring produced by generation 1 adults were then reared on Scenedesmus (generation 2), and life‐history traits were measured across both generations.

The results show that Daphnia in generation 1 exhibited reduced fitness (i.e., delayed maturation, lower reproductive output, increased clutch interval) when reared in the presence of cyanobacteria as opposed to high‐quality food. However, maternal stress had no clear influence on the fitness of offspring. That is, Daphnia in the second experimental generation had similar mean trait values, irrespective of whether their mothers were reared on cyanobacteria or high‐quality food.

Signals of transgenerational life‐history effects were obscured, in part, by extensive clonal variation among Daphnia in the direction of transgenerational responses to cyanobacteria (i.e., adaptive and maladaptive plasticity). Further analyses demonstrated that such individual variance in plasticity might be open to selection and potentially offer a means of contemporary adaptation to cyanobacteria. Taken together, our results denote a link between the overall strength of transgenerational responses to the environment and the potential for rapid evolution in populations.

A free Plain Language Summary can be found within the Supporting Information of this article.
The influence of landscape context on short‐ and long‐term forest change following a severe ice storm
Authors: Lloren Jed Immanuel , Fahrig Lenore , Bennett Joseph R. , Contreras Thomas A. , McCune Jenny L.
Published: July 2019

When deforestation results in small forest fragments surrounded by a non‐forest matrix, forest stands within these fragments experience changes in structure and community composition. They also continue to experience natural disturbances like hurricanes and ice storms. It remains unclear whether the landscape context of forest stands influences plant community response to natural disturbances.

Using data from surveys of forested plots in the years immediately following and 19 years after a severe ice storm, we measured changes in woody stem density, species richness and beta diversity.

Plots with greater storm damage had greater gains in stems and species, and greater shifts in community composition. In addition, there were interactions between the degree of storm damage and landscape context. The short‐term effects of storm damage were magnified in plots with less forest on the surrounding landscape and farther from the forest edge. In plots with high damage, a return towards pre‐storm conditions over the long‐term occurred more often in plots farther from the forest edge compared to those close to the edge.

Synthesis. Future climate scenarios predict increases in severe weather and accompanying ecosystem disturbance. Our results show that it is important to consider landscape context when assessing the response of forest communities to such disturbances.
From ‘There is No Alternative’ to ‘Maybe There are Alternatives’: five Challenges to Economic Orthodoxy after the Crash
Authors: Hunt Tom , Stanley Liam
Published: July 2019

Prior to the 2008 financial crisis, politicians famously told the public and themselves that ‘there is no alternative’ to a neoliberal economic paradigm. Fast‐forward to 2019 and there is, instead, the sense that ‘maybe there are alternatives’. However, when many observers and commentators look back to the 2008 crisis, they see a general continuity with what went before. In order to gain a better understanding of this ‘interregnum’, we map five sets of ideas and practices that challenge the policies, ideas, and conventions of pre‐crash orthodoxy. In doing so, we argue that there has been a fundamental transformation in legitimate public discourse about the economy since 2008: ideas and practices that were previously unimaginable or illegitimate in mainstream economic debate are now commonplace. Although this does not represent a ‘paradigm shift’, it represents significant political change that is important to understand and interrogate on its own terms.
Negligible risk of prenatal ductus arteriosus closure or fetal renal impairment after third‐trimester paracetamol use: evaluation of the German Embryotox cohort
Authors: Dathe K , Frank J , Padberg S , Hultzsch S , Meixner K , Beck E , Meister R , Schaefer C
Published: July 2019

Objective

Risk of fetotoxicity after paracetamol exposure in the third trimester.

Design

Observational cohort study and retrospective case assessment.

Setting

Germany, 2008–2017.

Population

Pregnant women exposed to paracetamol.

Methods

Prospectively enrolled third‐trimester pregnancies that had been exposed to paracetamol (604) were compared with pregnancies exposed to paracetamol in the first and/or second trimester only (1192). Exclusion criteria were exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs) in the second or third trimester. Additionally, the Embryotox ‘adverse drug reaction in pregnancy’ database was screened for cases of fetotoxicity.

Main outcome measures

The prenatal study end points focused on narrowing or closure of ductus arteriosus Botalli, late fetal death, and oligohydramnios. The postnatal end points included patent ductus arteriosus (PDA), primary pulmonary hypertension (PPHT), and impaired renal function.

Results

In both cohorts, no fetus with intrauterine narrowing or closure of the ductus arteriosus Botalli was reported (0/604 versus 0/1192). Oligohydramnios was diagnosed at a similar frequency in both cohorts: 1.3% (8/604) versus 1.6% (19/1192). There was one stillbirth in the study cohort (1/604, 0.2%) and four stillbirths in the comparison cohort (4/1192, 0.3%). The rates of PDA in neonates were similar: 0.7% (4/615) versus 0.7% (9/1212). PPHT as well as serious postnatal renal disorders were reported once in each cohort. In 12 out of 96 retrospective cases, there were indicators for study end points; however, co‐exposure to NSAIDs or complex situations weaken the assumption of paracetamol toxicity.

Conclusions

Fetal cardiovascular or renal toxicity of maternal third‐trimester paracetamol use appears to be negligible.

Tweetable abstract

Paracetamol use in the third trimester does not seem to be associated with a relevant risk of fetotoxicity.
An Efficient Ambient Ionization Mass Spectrometric Approach to Detection and Quantification of the Mescaline Content of Commonly Abused Cacti from the Echinopsis Genus
Authors: Longo Cameron M. , Musah Rabi A.
Published: July 2019

Unregulated cacti from the genus Echinopsis are used recreationally as mescaline‐containing alternatives to the outlawed peyote. Echinopsis‐derived plant materials appear in a variety of nondescript forms, making rapid assessment of whether they are mescaline‐containing materials or simply innocuous plant‐derived food products, very challenging. Reported here is a DART‐HRMS approach for the rapid detection of mescaline in whole plant material and a validated method for the quantification of mescaline in cactus tissue, using mescaline‐d9 as the internal standard. Calibration curves exhibited R2 values of ≥0.995, and the method exhibited a LLOQ and a linear range of 1 ppm and 1–100 ppm, respectively. Application of the method to commercially available Echinopsis spp. yielded results consistent with previous studies performed by GC‐ and LC‐MS, with mescaline levels of <2% dry weight in all cases. Therefore, DART‐HRMS is a suitable technique for the rapid screening of mescaline and its subsequent quantification within complex plant‐derived matrices.
Crosstalk between bacterial conjugation and motility is mediated by plasmid‐borne regulators
Authors: Luque Ainara , Paytubi Sonia , Sánchez‐Montejo Javier , Gibert Marta , Balsalobre Carlos , Madrid Cristina
Published: July 2019

Plasmid conjugation is a major horizontal gene transfer mechanism. The acquisition of a plasmid may cause a perturbation of the cell functions in addition to provide advantageous properties for the recipient cell, such as the gaining of antibiotic resistances. The interplay between plasmid and chromosomal functions has been studied using the IncHI1 plasmid R27. Plasmids of the incompatibility group HI1, isolated from several Gram‐negative pathogens, are associated with the spread of multidrug resistance. Their conjugation is tightly regulated by temperature, being repressed at temperatures within the host (37°C). In this report, we described that at permissive temperature, when conjugation of plasmid R27 is prompted, a reduction in the motility of the cells is observed. This reduction is mediated by the plasmid‐encoded regulators TrhR/TrhY, which together with HtdA form a plasmid‐borne regulatory circuit controlling R27 conjugation. TrhR/TrhY, required to induce R27 conjugation, is responsible for the downregulation of the flagella synthesis and the consequent decrease in motility. TrhR/TrhY repress, direct or indirectly, the expression of the specific flagellar sigma subunit FliA and, consequently, the expression of all genes located bellow in the flagellar expression cascade.
Dentinal dysplasia type 1: A 3D micro‐computed tomographic study of enamel, dentine and root canal morphology
Authors: Ranjitkar Sarbin , Yong Robin , Wu I‐Cheng , Gully Grant , Farmer Daniel , Watson Ian , Heithersay Geoffrey
Published: July 2019

Dentine dysplasia type 1 is a rare and complex dental anomaly. Our aim was to conduct a morphometric assessment of a dentinal dysplasia type 1c (DD1c) caries‐free mandibular second molar, extracted due to symptomatic apical periodontitis. Controls consisted of five intact mandibular second molars. Micro‐computed tomography analysis showed that the DD1c volume % for enamel, dentine/cementum and pulp chamber fell in the 0.36th, 99.97th and 0.09th percentiles of the control teeth (P < 0.01). It also revealed an extremely complicated root canal system in the DD1c tooth with a varying degree of dentine mineralisation and aberrant dentine deposition in the pulp chamber. A crack extending from the external tooth surface to the pulp chamber was identified as a potential site for microbial invasion. Clinical implications include preventive measures and early intervention in reversible pulpitis. Conclusion: Micro‐CT imaging can be useful in establishing post‐extraction diagnosis of cracks and phenomic characterisation of tooth anomalies.
Predictors of clinically urgent intracranial pathology at neuroimaging in children with complex febrile seizures: a retrospective cross‐sectional study
Authors: Guillou Tifenn , Carbajal Ricardo , Rambaud Jérome , Titomanlio Luigi , de Pontual Loic , Biscardi Sandra , Nissack‐Obiketeki Gisèle , Pellegrino Béatrice , Charara Oussama , Angoulvant François , Denis Julien , Chalard Francois , Morel Baptiste , Loschi Solène , Chappuy Hélène , Guedj Romain
Published: July 2019

Aim

To assess the prevalence of clinically urgent intracranial pathology (CUIP) in children visiting the emergency department with a complex febrile seizure (CFS).

Methods

Retrospective cohort review. We analysed the visits of patients for a CFS from January 2007 to December 2011 in seven paediatric emergency departments. Our main outcomes were the proportions of CUIP diagnosed between day 0 and 1 and within 30 days after the index visit.

Results

From 1 183 487 visits, 839 were for a CFS and 130 (15.5%) of these had a neuroimaging performed within 30 days (CT scan for 75 visits [8.9%], MRI for 30 visits [3.6%] and both for 25 visits [3.0%]). Three CUIP were diagnosed between day 0 and 1 (0.4% [CI‐95%: 0.1‐1.3]), 5 within 30 days after the index visit (0.7% [CI‐95%: 0.2‐1.7]) but none among the 630 visits of children presenting with a normal neurological clinical examination (0% [95% CI: 0.0‐0.7]), nor among the 468 presenting only with multiple seizure (0% [95% CI: 0.0‐1.0]).

Conclusion

In children with a CFS, CUIP is rare event in the subgroup of children with a normal neurological clinical examination and in those with brief generalised multiple seizures.
Drug information centre queries and responses about drug interactions over 10 years—A descriptive analysis
Authors: Tukukino Carina , Wallerstedt Susanna M.
Published: July 2019

Many people are treated with ≥1 drug, implying that risks of drug interactions need to be considered. The aim of this study was to describe drug interaction queries from healthcare professionals to a drug information centre in Sweden over 10 years focusing on drugs frequently asked about and the advice provided. Advice was recorded in mutually exclusive groups: Avoid, Adjust dose, Separate intake, Vigilance or No problem. For queries with Avoid, Adjust dose or Separate intake advice, alerts were extracted from an interaction database (Janusmed). Of 4335 queries to the centre in 2008‐2017, 589 (14%) concerned interactions. Most were posed by physicians (91%) and concerned a specific patient (83%) before treatment initiation (76%). Sertraline, warfarin and methotrexate were the most frequently asked about, whereas queries about cyclophosphamide and rifampicine occurred most often in relation to the number of exposed patients. Advice provided in 557 (95%) replies comprised Avoid: n = 85 (15%), Adjust dose: n = 57 (10%), Separate intake: n = 17 (3%), Vigilance: n = 235 (42%) or No problem: n = 163 (29%). In all, 113 (71%) of 159 queries with Avoid/Adjust dose/Separate intake advice elicited an action alert on Janusmed, whereas 31 (20%) did not result in any alert at all. Summarized, seven in ten replies from the drug information centre recommended an explicit drug treatment action, regarding either specific prescribing aspects, for instance dose adjustments, or active follow‐up including monitoring potential adverse reactions and/or laboratory results. Readily accessible decision support regarding drug interactions often provides relevant action alerts, but cannot be solely relied on.
Hypoxic augmentation: The tale of a strange contraction
Authors: Vanhoutte Paul Michel , Leung Susan Wai Sum
Published: July 2019

Almost fifty years ago, experiments on isolated veins showed that acute hypoxia augments venoconstrictor responses in vitro and that such facilitation relied on anaerobic glycolysis. Over the years, this phenomenon was extended to a number of arterial preparations of different species and revisited, from a mechanistic point of view, with the successive demonstration that it depends on calcium handling in the vascular smooth muscle cells, is endothelium‐dependent and requires the production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) and the activation of soluble guanylyl cyclase (sGC). However, rather than the vasodilator cyclic nucleotide 3′,5′‐cyclic guanosine monophosphate (cGMP), its canonical product, the latter enzyme produces 3′,5′‐cyclic inosine monophosphate (cIMP) instead during acute hypoxia; this non‐canonical cyclic nucleotide facilitates the contractile process in the vascular smooth muscle cells. This ‘biased’ activity of soluble guanylyl cyclase appears to involve stimulation of NAD(P)H:quinone oxidoreductase 1 (NQO‐1). The exact interactions between hypoxia, anaerobic metabolism and NQO‐1 leading to biased activity of soluble guanylyl cyclase remain to be established.
FAS‐mediated apoptosis impairment in patients with ALPS/ALPS‐like phenotype carrying variants on CASP10 gene
Authors: Miano Maurizio , Cappelli Enrico , Pezzulla Agnese , Venè Roberta , Grossi Alice , Terranova Paola , Palmisani Elena , Maggiore Rosario , Guardo Daniela , Lanza Tiziana , Calvillo Michaela , Micalizzi Concetta , Pierri Filomena , Vernarecci Chiara , Beccaria Andrea , Corsolini Fabio , Lanciotti Marina , Russo Giovanna , Ceccherini Isabella , Dufour Carlo , Fioredda Francesca
Published: July 2019

Autoimmune lymphoproliferative syndrome (ALPS) is a congenital disorder that results in an apoptosis impairment of lymphocytes, leading to chronic lymphoproliferation and autoimmunity, mainly autoimmune cytopenias. FAS gene defects are often responsible for the disease, the phenotype of which can vary from asymptomatic/mild forms to severe disease. More rarely, defects are associated to  other genes involved in apoptosis pathway, such as CASP10. Few data are available on CASP10‐mutated patients. To date, two CASP10 mutations have been recognized as pathogenic (I406L and L258F) and others have been reported with controversial result on their pathogenicity (V410l, Y446C) or are known to be polymorphic variants (L522l). In this study, we evaluated apoptosis function in patients with an ALPS/ALPS‐like phenotype carrying CASP10 variants. Molecular findings were obtained by next generation sequencing analysis of genes involved in immune dysregulation syndromes. Functional studies were performed after inducing apoptosis by FAS‐ligand/TRIAL stimulation and analysing cell death and the function of CASP10, CASP8 and PARP proteins. We identified 6 patients with an ALPS (n = 2) or ALPS‐like (n = 4) phenotype, carrying I406L (n = 1),V410l (n = 2),Y446C (n = 1) heterozygous CASP10 variants or the L522l polymorphisms (n = 2) associated with another polymorphic homozygote variant on CASP8 or a compound heterozygous mutation on TNFRSF13C. Apoptosis was impaired in all patients showing that such variants may play a role in the development of clinical phenotype.
Effect of moderate exercise under hypoxia on Th1/Th2 cytokine balance
Authors: Santos Samile A. , Lira Fábio S. , Silva Edgar T. , Caris Aline V. , Oyama Lila M. , Thomatieli‐Santos Ronaldo V.
Published: July 2019

Introduction and objective

Moderate exercise performed in normoxia can be immunostimulatory, while strenuous exercise can be immunosuppressive. However, less is known about the effects of exercise under hypoxia on cytokines. The aim of this study was to evaluate the effects of an acute exercise session performed under hypoxia similar to an altitude of 4200 m on cytokine balance. Our hypothesis was that exercise, even of moderate intensity, associated with hypoxia may induce different changes in relation to the normoxic condition.

Methods

Eight healthy male volunteers were exercised on a treadmill for 1 hour at an intensity of 50% VO2peak under normoxic or hypoxic condition (4200 m). Blood samples were collected at rest and immediately 1 hour after the exercise, respectively to determine cytokines, hormones and metabolites. The two‐way ANOVA and the Bonferroni post hoc test were used and the significance adopted was P < .05.

Results

While IL‐2, the IL‐2/IL‐4 ratio and glutamine decreased under hypoxia, IL‐6 and IL‐1ra increased. There were increases in the IL‐2/IL‐4 ratio, IL‐6, IL‐1ra and IL‐10/TNF‐α in normoxia. There were no differences in cortisol or glucose.

Conclusion

Moderate exercise under hypoxia condition changes the Th1/Th2 balance including IL‐2, IL‐4 and TNF‐α cytokines, suggesting a Th2 response after 1 hour rest.
Ecological correlates of extinction risk in Chinese amphibians
Authors: Chen Chuanwu , Chen Cangsong , Wang Yanping
Published: July 2019

Aim

China is one of the countries with the richest amphibian biodiversity in the world. Among the 408 Chinese amphibians, 174 species are considered threatened according to the China Biodiversity Red List in 2015. However, to date, which species traits or extrinsic factors are correlated with extinction risk in Chinese amphibians is rarely examined. The aims of this study were thus to identify the patterns and correlates of extinction risk in Chinese amphibians and to determine whether patterns and processes are similar between species with either small or large geographic distributions.

Location

China.

Methods

We obtained twelve species traits and four extrinsic factors that have been commonly linked to the extinction risk of amphibians. After phylogenetic correction, these factors were tested separately and in combination to identify their correlations with extinction risk in all Chinese amphibians, and in small‐ranged and large‐ranged species.

Results

Geographic range size and elevational range were the most important predictors of extinction risk in all Chinese amphibians. Although extinction risk in small‐ranged amphibians was predominantly determined by small elevational range, in large‐ranged amphibians it was driven by geographic and elevational ranges, body size, human exploitation index and adult microhabitat. Small‐ranged amphibians had a higher percentage of threatened species than large‐ranged species. However, the body size distributions were not statistically different between these two amphibian subgroups.

Main conclusions

Our findings suggest that conservation priority should be given to species with small geographic and elevational ranges. Small‐ranged and large‐ranged amphibians should be conserved with different strategies because the factors influencing extinction risk differ between these two groups. In specific, the reduction of habitat loss should be a primary focus of management efforts because species with small geographic and elevational ranges are particually vulnerable to habitat loss. Conservation efforts should also focus on protecting large‐bodied species and preventing human overexploitation for the effective conservation of large‐ranged amphibians.
Spatial and temporal patterns and the socioeconomic impacts of landslides in the tropical and mountainous Colombian Andes
Authors: Aristizábal Edier , Sánchez Oscar
Published: July 2019

Landslides are a natural hazard that presents a major threat to human life and infrastructure. Although they are a very common phenomenon in Colombia, there is a lack of analysis that entails national and comprehensive spatial, temporal, and socioeconomic evaluations of such events based on historical records. This study provides a detailed assessment of the spatial and temporal patterns and the socioeconomic impacts associated with landslides that occurred in the country between 1900 and 2018. Two national landslide databases were consulted and this information was complemented by local and regional landslide catalogues. A total of 30,730 landslides were recorded in the 118‐year period. Rainfall is the most common trigger of landslides, responsible for 92 per cent of those registered, but most fatalities (68 per cent) are due to landslides caused by volcanic activity and earthquakes. An ‘fN curve’ revealed a very high frequency of small and moderate fatal landslides in the time frame.
Differences in treatment and monitoring of chronic myeloid leukemia with regard to age, but not sex: Results from a population‐based study
Authors: Lauseker Michael , Gerlach Roman , Worseg Wenke , Haferlach Torsten , Tauscher Martin , Hasford Joerg , Hoffmann Verena S.
Published: July 2019

There are established guidelines for treatment and monitoring of chronic myeloid leukemia (CML) but little is known about routine care. Data on ICD‐10 codes as well as prescribed medications were available for 10.5 million patients in the statutory health insurance system in Bavaria for the years 2010 to 2016. Also, data on the molecular and cytogenetic monitoring were integrated. A total of 1714 adult patients with CML were observed. Only 50.8% received more than 67.5 daily doses per quarter year (target: 91.5) while 18.2% did not receive any tyrosine kinase inhibitor (TKI). The median number of daily doses was at least 80 doses per quarter year for all age groups in men, but decreased to 62 doses in elderly women. With this exception, no differences between men and women were observed. The percentage of patients without any TKI increased with age. The median number of molecular examinations was 3.54 independent of age and sex. Even in a highly developed country, still a considerable number of patients with CML seem to not receive adequate treatment, whereas molecular monitoring can be considered satisfactory.
Safety of tapering tacrolimus dose in patients with well‐controlled anti‐acetylcholine receptor antibody‐positive myasthenia gravis
Authors: Nishida Y. , Takahashi Y. K. , Kanai T. , Nose Y. , Ishibashi S. , Sanjo N. , Uzawa A. , Oda F. , Ozawa Y. , Kuwabara S. , Noguchi E. , Suzuki S. , Nakahara J. , Suzuki N. , Ogawa T. , Yokoyama K. , Hattori N. , Konno S. , Fujioka T. , Kawaguchi N. , Hatanaka Y. , Sonoo M. , Kaneko J. , Ogino M. , Nishiyama K. , Nomura K. , Yokota T.
Published: July 2019

Background and purpose

Tapering immunosuppressants is desirable in patients with well‐controlled myasthenia gravis (MG). However, the association between tapering of calcineurin inhibitor dosage and reduction‐associated exacerbation is not known. The aim of this study was to clarify the frequency of reduction‐associated exacerbation when tacrolimus is tapered in stable patients with anti‐acetylcholine receptor antibody‐positive MG, and to determine the factors that predict exacerbations.

Methods

We retrospectively analyzed 115 patients in whom tacrolimus dosage was tapered. The reduction‐associated exacerbation was defined as the appearance or worsening of one or more MG symptoms <3 months after the reduction.

Results

Tacrolimus dosage was successfully tapered in 110 patients (96%) without any exacerbation. Five patients (4%) experienced an exacerbation, but symptoms were reversed in all patients when the tacrolimus dose was increased to the previous maintenance level. No patient developed an MG crisis. The age at onset was significantly earlier (30 vs. 56 years, P = 0.025) and the reduction in dosage was significantly larger (2.0 vs. 1.0 mg/day, P = 0.002) in patients with reduction‐associated exacerbation than in those without exacerbation. The cut‐off values determined in a receiver‐operating characteristic curve analysis were 52 years (sensitivity, 57%; specificity, 100%) for the age at onset and 1.5 mg (sensitivity, 80%; specificity, 100%) for the dose reduction.

Conclusion

Tapering of tacrolimus was possible in most patients with well‐controlled anti‐acetylcholine receptor antibody‐positive MG. Early age at onset and a large reduction from maintenance dosage were associated with exacerbation. Reductions ≤1.5 mg/day from the maintenance dosage should be considered for patients with late‐onset disease.
Why is the gender revolution uneven and stalled? Gender essentialism and men's movement into ‘women's work'
Authors: Moskos Megan
Published: July 2019

Men's limited movement into female occupations has been identified as a key barrier to future declines in occupational sex segregation and achieving greater gender equality. So why are men so reticent to enter jobs normatively regarded as female? Drawing from qualitative interviews with multiple stakeholders in four female‐dominated occupations in Australia, this article documents the processes that influence men's employment in gender‐atypical jobs. Gender essentialism is central to many processes that generate and/or stall changes in men's representation in female‐dominated occupations. While gender essentialism's role in producing and reproducing occupation sex segregation is well known, its role in reducing occupational sex segregation is a critical process which has previously received limited attention. The article details gender essentialism's integrative function.
Raynaud's Phenomenon Associated With Calcitonin Gene‐Related Peptide Monoclonal Antibody Antagonists
Authors: Evans Randolph W.
Published: July 2019

Two cases are reported of migraineurs who reported Raynaud's phenomenon (RP) exacerbated while taking monoclonal antibodies to the calcitonin gene‐related peptide (CGRP) ligand (fremanezumab and galcanezumab) and 1 case of new onset RP while taking the CGRP receptor antagonist (erenumab). The prevalence of primary and secondary RP, causes of secondary RP, co‐morbidity with migraine, and medications which might induce or exacerbate RP are reviewed. The pathophysiology of how CGRP monoclonal antagonists might exacerbate or induce RP is discussed. The cases suggest but do not prove causation.
Gene expression of growth factors with angiogenic potential in human dental pulp tissue from teeth with complete and incomplete root development
Authors: Gomez‐Sosa J. F. , Caviedes‐Bucheli J. , Diaz‐Barrera L. E. , Munoz H. R.
Published: July 2019

Aim

To quantify the expression of angiogenic growth factors (ANG2, VEGFA, TGFß1) and their corresponding receptors (VEGFR1, VGFR2, NRP1 and TGFßR1) in human dental pulps from extracted third molars with complete and incomplete root development.

Methodology

Fifty‐six dental pulp samples obtained from freshly extracted human third molars were divided equally into two groups according to their stage of root development; 28 third molars with complete root development and 28 third molars with incomplete root development. All samples were processed and total RNA was extracted, cDNA was then synthetized for each sample and the target genes expression profiles for ANG2, VEGFA, VEGFR1, VEGFR2, NRP1, TGFß1 and TGFßR1 were obtained by RT2‐PCR. The data was analysed with a Student's t‐test to compare the replicate ∆∆Ct values for each gene.

Results

Teeth with incomplete root development were associated with a significantly greater gene expression of TGFβR1 (P = 0.03), whereas in teeth with complete root development the genes that had significantly greater expression were VEGFA (P = 0.04).

Conclusion

The angiogenic growth factors (ANG2, VEGFA, TGFβ1) and their receptors (NRP1, VEGFR1, VEGFR2 and TGFßR1) were expressed in pulps of teeth with complete and incomplete root development measured by RT2‐PCR, with TGFBR1 genes being significantly different in teeth with incomplete root development and VEGFA genes in teeth with complete root development.
Collaborative network to take responsibility for oral anticancer therapy (CONTACT): Study‐protocol investigating the impact of a care pathway
Authors: Kinnaer Lise‐Marie , Decoene Elsie , Van Hecke Ann , Foulon Veerle
Published: July 2019

Aim

To evaluate the effectiveness, feasibility, meaningfulness and appropriateness of the development and implementation of a transmural care pathway in four hospitals in Flanders to improve self‐management support in healthcare professionals and self‐management in patients treated with oral anticancer drugs.

Design

A multicentre, prospective, interventional before‐after study.

Method

The development and implementation of the care pathway is based on the 7‐phase method by Vanhaecht et al. (2012). Before and after, the care process will be evaluated from the perspective of patients, healthcare professionals in the hospital and from primary care and the available evidence. In both study‐parts, a mixed methods approach will be used including observations, semi‐structured interviews, focus groups and validated questionnaires for outcome assessments. The primary outcome is self‐management in patients and self‐efficacy and perception towards self‐management in healthcare professionals. This study was funded in October 2015 and has been approved by the Ethics Committee in June 2016.

Discussion

Due to the growing number of patients taking oral anticancer drugs, there is need for a rigorous study that aims to optimize self‐management in patients and self‐management support provided by an interdisciplinary team of healthcare professionals (including oncology nurses and clinical nurse specialists). The care pathway should therefore consist of effective self‐management supporting interventions and should clearly define the role of all stakeholders.

Impact

This study attempts to obtain standardization, uniformity and continuity of self‐management support provided by healthcare professionals to patients on oral anticancer drugs with the aim to achieve an adequate level of self‐management.

Trial registration: clinicaltrials.gov NCT02861209.
Medical reasoning and doctor‐patient communication
Authors: Stanley Donald E. , Sehon Scott R.
Published: July 2019

Nineteenth‐century American philosopher Charles Sanders Peirce offered a picture of the scientific method that can be fruitfully applied to the practice of medical diagnosis. Physicians can use this framework to become more self‐consciously aware of what they are doing when they diagnose medical conditions, and they can also learn more about the potential pitfalls of communication between physicians and their patients.
Individual behaviour and resource use of thermally stressed brook trout Salvelinus fontinalis portend the conservation potential of thermal refugia
Authors: White Shannon L. , Kline Benjamen C. , Hitt Nathaniel P. , Wagner Tyler
Published: July 2019

Individual aggression and thermal refuge use were monitored in brook trout Salvelinus fontinalis in a controlled laboratory to determine how fish size and personality influence time spent in forage and thermal habitat patches during periods of thermal stress. On average, larger and more exploratory fish initiated more aggressive interactions and across all fish there was decreased aggression at warmer temperatures. Individual personality did not explain changes in aggression or habitat use with increased temperature; however, larger individuals initiated comparatively fewer aggressive interactions at warmer temperatures. Occupancy of forage patches generally declined as ambient stream temperatures approached critical maximum and fish increased thermal refuge use, with a steeper decline in forage patch occupancy observed in larger fish. These findings suggest that larger individuals may be more vulnerable to stream temperature rise. Importantly, even at thermally stressful temperatures, all fish periodically left the thermal refuge to forage. This indicates that the success of refugia at increasing population survival during periods of stream temperature rise may depend on the location of thermal refugia relative to forage locations within the larger habitat mosaic. These results provide insights into the potential for thermal refugia to improve population survival and can be used to inform predictions of population vulnerability to climate change.
Further evaluation of the efficacy of emamectin benzoate for treating Pseudocapillaria tomentosa (Dujardin 1843) in zebrafish Danio rerio (Hamilton 1822)
Authors: Kent Michael L. , Watral Virginia , Gaulke Christopher A. , Sharpton Thomas J.
Published: July 2019

Pseudocapillaria tomentosa is a pathogenic nematode parasite, causing emaciation and severe inflammatory lesions in the intestines in zebrafish Danio rerio (Hamilton 1822). Emamectin benzoate is commercially available analogue of ivermectin used for treating salmon for sea lice, under the brand name SLICE®, and we have used this for treating zebrafish with the P. tomentosa. Here, SLICE®, 0.2 per cent active emamectin benzoate, was used for oral treatments at 0.35 mg emamectin benzoate/kg fish/day for 14 days starting at 7 days post‐exposure (dpe). Another experiment entailed initiating treatment during clinical disease (starting at 28 dpe). Early treatment was very effective, but delaying treatment was less so, presumably due to inappetence in clinically affected fish. We evaluated emamectin benzoate delivered in water, using Lice‐Solve™ (mectinsol; 1.4% active emamectin benzoate) in two experiments. Application of four 24‐hr treatments, space over 7 days was initiated at 28 dpe at either 0.168 or 0.56 mg emamectin benzoate/L/bath, and both treatments completely eradicated infections. This was 3 or 10 times manufacture's recommended dose, but was not associated with clinical or histological side effects.
The impact of living with home enteral feeding: perspectives of people who have had a diagnosis of head and neck cancer
Authors: Thomas A. , Sowerbutts A. M. , Burden S. T.
Published: July 2019

Background

The number of people with head and neck cancer who are home enterally fed continues to grow each year. Insertion of a feeding tube is common place in these patients and is considered to have a detrimental effect on quality of life. The present study aimed to investigate the daily impact of home enteral feeding (HEF) from the perspective of people who have had a diagnosis of head and neck cancer.

Methods

The methodology aligned with interpretative phenomenology analysis. People who were home enterally fed, with head and neck cancer, and aged ≥18 years were recruited. Data were collected using semi‐structured interviews and analysis focused on what the daily impact of HEF meant for participants.

Results

Data saturation was achieved after interviewing 15 participants. Five cluster themes were identified. ‘Deviation from the norm’ encompassed change and loss of normality. ‘Regaining control leading to empowerment’ encompassed participant empowerment through development of new skills and adjusting the feeding regime. ‘Creating a new normal’ involved making adjustments to facilitate inclusion and participation. ‘External modifiers of the HEF experience’ and ‘internal modifiers of the HEF experience’ encompassed the identification of external and internal HEF factors that influenced HEF adaptation.

Conclusions

HEF was found to influence peoples’ daily lives substantially and required extensive adjustments for individuals to find a new normal. A greater level of interpretation was provided beyond the current evidence‐base for this group. Policymakers and clinicians should recognise the wider impact of HEF and ensure that this awareness is embedded in clinical practice.
Histopathological changes in tumor budding between biopsy and resected specimens from patients treated with preoperative S‐1 chemotherapy for oral cancer
Authors: Seki‐Soda Mai , Sano Takaaki , Koshi Hiromi , Yokoo Satoshi , Oyama Tetsunari
Published: July 2019

Background

S‐1 is an oral anticancer agent containing tegafur, a prodrug of 5‐fluorouracil (5‐FU). Preoperative S‐1 chemotherapy is performed to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the effects of preoperative S‐1 chemotherapy on tumor budding.

Methods

We examined 248 cases of OSCC and evaluated the budding scores in biopsy and resected specimens by keratin immunohistochemistry.

Results

In S‐1‐untreated patients, the budding scores in resected specimens tended to show a mild increase. S‐1 treatment had the effect of lowering the budding score, although some cases with dramatically increased budding scores in resected specimens were found in the early phase of administration. Relapse‐free survival showed a significant difference (P < .01) according to the presence or absence of S‐1 treatment among patients with high budding scores.

Conclusions

The present findings indicate that S‐1 administration may be more effective in patients with high budding scores than in those with lower budding scores.
GHSR‐1 agonist sensitizes rat colonic intrinsic and extrinsic neurons to exendin‐4: A role in the manifestation of postprandial gastrointestinal symptoms in irritable bowel syndrome?
Authors: Buckley Maria M. , O'Brien Rebecca , Buckley Julliette M. , O'Malley Dervla
Published: July 2019

Background

Patients with irritable bowel syndrome (IBS) may experience postprandial symptom exacerbation. Nutrients stimulate intestinal release of glucagon‐like peptide 1 (GLP‐1), an incretin hormone with known gastrointestinal effects. However, prior to the postprandial rise in GLP‐1, levels of the hunger hormone, ghrelin, peak. The aims of this study were to determine if ghrelin sensitizes colonic intrinsic and extrinsic neurons to the stimulatory actions of a GLP‐1 receptor agonist, and if this differs in a rat model of IBS.

Methods

Calcium imaging of enteric neurons was compared between Sprague Dawley and Wistar Kyoto rats. Colonic contractile activity and vagal nerve recordings were also compared between strains.

Key Results

Circulating GLP‐1 concentrations differ between IBS subtypes. Mechanistically, we have provided evidence that calcium responses evoked by exendin‐4, a GLP‐1 receptor agonist, are potentiated by a ghrelin receptor (GHSR‐1) agonist, in both submucosal and myenteric neurons. Although basal patterns of colonic contractility varied between Sprague Dawley and Wister Kyoto rats, the capacity of exendin‐4 to alter smooth muscle function was modified by a GHSR‐1 agonist in both strains. Gut‐brain signaling via GLP‐1–mediated activation of vagal afferents was also potentiated by the GHSR‐1 agonist.

Conclusions & Inferences

These findings support a temporal interaction between ghrelin and GLP‐1, where the preprandial peak in ghrelin may temporarily sensitize colonic intrinsic and extrinsic neurons to the neurostimulatory actions of GLP‐1. While the sensitizing effects of the GHSR‐1 agonist were identified in both rat strains, in the rat model of IBS, underlying contractile activity was aberrant.
Electroencephalography theta/beta ratio covaries with mind wandering and functional connectivity in the executive control network
Authors: van Son Dana , de Rover Mischa , De Blasio Frances M. , van der Does Willem , Barry Robert J. , Putman Peter
Published: July 2019

The ratio between frontal resting‐state electroencephalography (EEG) theta and beta frequency power (theta/beta ratio, TBR) is negatively related to cognitive control. It is unknown which psychological processes during resting state account for this. Increased theta and reduced beta power are observed during mind wandering (MW), and MW is related to decreased connectivity in the executive control network (ECN) and increased connectivity in the default mode network (DMN). The goal of this study was to test if MW‐related fluctuations in TBR covary with such functional variation in ECN and DMN connectivity and if this functional variation is related to resting‐state TBR. Data were analyzed for 26 participants who performed a 40‐min breath‐counting task and reported the occurrence of MW episodes while EEG was measured and again during magnetic resonance imaging. Frontal TBR was higher during MW than controlled thought and this was marginally related to resting‐state TBR. DMN connectivity was higher and ECN connectivity was lower during MW. Greater ECN connectivity during focus than MW was correlated to lower TBR during focus than MW. These results provide the first evidence of the neural correlates of TBR and its functional dynamics and further establish TBR's usefulness for the study of executive control, in normal and potentially abnormal psychology.
Nano‐WO3‐SO3H as a New Photocatalyst Insight Through Covalently Grafted Brønsted Acid: Highly Efficient Selective Oxidation of Benzyl Alcohols to Aldehydes
Authors: Hosseini Saber , Amoozadeh Ali , Akbarzadeh Yasaman
Published: July 2019

Modification of nano‐WO3 with −SO3H groups as a covalently grafted solid acid reduced its band‐gap energy from 2.8 to 2.4 eV and made it an ideal nominee for photocatalytic reaction under visible light irradiation. This nano‐photocatalyst has been successfully used for the selective oxidation of different benzyl alcohols to corresponding aldehydes under blue LED irradiation. The reaction became approximately two times faster with excellent yields. It has shown that the nitrobenzene as an available industrial oxidant is applicable for photocatalytic oxidation of benzyl alcohol; remarkably high yield and selectivity have been observed.
Myocardial fibrosis in chagas disease and molecules related to fibrosis
Authors: Chaves Ana T. , Menezes Cristiane A. S. , Costa Henrique S. , Nunes Maria C. P. , Rocha Manoel O. C.
Published: July 2019

Chronic Chagas cardiomyopathy (CCC) is responsible for the disease's greater morbidity and poor prognosis. Although understanding the pathophysiology of CCC and the fundamentals of its clinical management derives from research related to other cardiomyopathies, there are peculiarities that distinguish CCC from the others. CCC is the most fibrous heart disease, and its myocardial involvement is important as it disorganizes or disrupts the extracellular matrix, creating an environment conducive to the formation of arrhythmogenic foci. It is also considered the most arrhythmogenic of the known heart diseases, giving rise to complex arrhythmias, usually associated with varying degrees of stimulus conduction disorders. The central proposal of this review is to describe a possible association between the distribution and degree of myocardial fibrosis and cardiac arrhythmogenicity in patients with Chagas cardiomyopathy, drawing attention to the importance of noninvasive biomarkers for the quantification of myocardial fibrosis.
Introduction: The cultural and material worlds of mining in early modern Europe
Authors: Asmussen Tina , Long Pamela O.
Published: July 2019

This special issue is dedicated to the cultural values and impacts of the early modern mining industry and some of the enterprises and practices that surrounded them. The contributions enquire into how mining and metallurgy became a key sector in early modern European society, not only in terms of economic prosperity with its utilitarian connotations, but as a sociocultural phenomenon, whose materials and products affected, or even enabled, many areas of life and rulership. The authors' contributions focus on places, materials, and processes, and assess how historical actors engaged with metallic materials, both under and above the ground. They analyse human engagement with mined materials not simply from an economic perspective, but also as an administrative and legal praxis, a technological challenge, an environmental problem, a spiritual engagement, and an affective experience. This approach affords a broader perspective which expands the history of mining beyond the narrow sense of a history of material extraction, one that crosses the borders of the European mining regions and takes activities in urban hubs and on the sea into consideration as well.
Diving engines, submarine knowledge and the ‘wealth fetch’d out of the sea’
Authors: Hellawell Philippa
Published: July 2019

This article examines the motives for human intervention into the submarine, using the seventeenth‐century diving engine to consider the epistemic and economic incentives for venturing under water. It shows how diving engines and other underwater technologies were imbued with the associated promises of gaining new submarine knowledge as well as the quest for retrieving precious materials from the bottom of the sea. Setting diving engines against learned attitudes towards the submarine and the challenges of experience in knowledge‐making, it moves to consider the external, commercial influences on the experimental philosopher and the consequences this has for notions of disinterestedness. It argues that diving engines should be understood within the pursuits of both knowledge and profit, for the submarine, like the subterranean, was an environment to be both studied and exploited.
Productivity, Infrastructure and Urban Density—An Allometric Comparison of Three European City Regions Across Scales
Authors: Arbabi Hadi , Mayfield Martin , McCann Philip
Published: July 2019

Agglomeration-based arguments citing Dutch and German city regions have been a primary driver in advocating intercity transport strategies in the north of England. We adopt an allometric urban model investigating the applicability and transferability of these transport-led agglomerative strategies promoted to address England’s regional economic underperformance. This is undertaken through a comparative study of the size–cost performance balance of three city regions and the overall urban networks in the Netherlands and Germany, and England and Wales by using city units defined at different spatial scales. Although our results support a case for better mobility and transport comparing the three urban networks regardless of the spatial scales, comparisons of specific city regions indicate a more nuanced interplay of productivity, mobility infrastructure and urban density.