bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive life planning in women after kidney or liver transplantation
Authors: Szpotanska‐Sikorska Monika , Mazanowska Natalia , Madej Anna , Kociszewska‐Najman Bozena , Wielgos Miroslaw , Pietrzak Bronislawa
Published: August 2018

Introduction

To estimate reproductive life planning in post‐transplant women and to identify factors affecting their pregnancy intentions.

Material and Methods

A survey study on reproductive life planning was conducted in 217 women of childbearing age who underwent kidney or liver transplantation. The results were compared with data obtained from 816 healthy women surveyed by the Polish Centre for Public Opinion Research. Data were summarized using descriptive statistics.

Results

Post‐transplant women express a similar desire to have a child as women in the general population (42% vs 40%, respectively; P = 0.638). A comparable majority of childless women would like to give birth (65% vs 77%, P = 0.350). More post‐transplant women who have one child give up on future procreation plans (80% vs 46%, P < 0.001). The main factors affecting post‐transplant reproductive life planning were age (OR:0.79; 95% CI: 0.73‐0.85), number of live births (OR:0.22; 95% CI: 0.11‐0.43), and use of drugs contraindicated in pregnancy (OR:0.27; 95% CI: 0.11‐0.63).

Conclusions

Women after kidney or liver transplantation, especially childless, have a similar willingness to become mothers as those in the general population. For post‐transplant women who have already given birth, it is worth considering contraceptive counseling because these women more often choose to not attempt another pregnancy.
Is insulin pump therapy effective in Type 1 diabetes?
Authors: Pickup J. C.
Published: August 2018

There continues to be uncertainty about the effectiveness in Type 1 diabetes of insulin pump therapy (continuous subcutaneous insulin infusion, CSII) vs. multiple daily insulin injections (MDI). This narrative review discusses the reasons for this uncertainty, summarizes the current evidence base for CSII and suggests some future research needs. There are difficulties in interpreting trials of CSII because effectiveness varies widely due to factors such as differing baseline control, suboptimal use of best CSII practices, and psychological factors, for example, high external locus of control, non‐adherence and lack of motivation. Many summary meta‐analyses are also misleading because of poor trial selection (e.g. short duration, obsolete pumps, low baseline rate of hypoglycaemia) and reliance on mean effect size for decision‐making. Both MDI and CSII can achieve strict glycaemic control without hypoglycaemia in some people with Type 1 diabetes, especially those who are motivated and have undergone structured diabetes education, and with high levels of ongoing input from healthcare professionals. CSII is particularly effective in those people with Type 1 diabetes who have not achieved target HbA1c levels without disabling hypoglycaemia using best attempts with MDI, and here there can be valuable and substantial improvement. Insulin pumps are safe, effective and accepted when used in newly diagnosed diabetes, particularly in children, where MDI may not be practicable. Future research needs include more studies on mortality associated with insulin pumps where registry data have suggested lower rates vs. MDI; and psychological strategies to improve non‐adherence and suboptimal glycaemic outcomes on CSII.
A qualitative study exploring women's health behaviours after a pregnancy with gestational diabetes to inform the development of a diabetes prevention strategy
Authors: Parsons J. , Sparrow K. , Ismail K. , Hunt K. , Rogers H. , Forbes A.
Published: August 2018

Aim

To inform targeted interventions for women with gestational diabetes mellitus (GDM) by exploring the factors that influence their health behaviours and their preferences for lifestyle support.

Methods

Participants were women with previous GDM taken from a diverse inner‐city UK population. Data collection involved focus groups (n = 35 women in six groups) and semi‐structured interviews (n = 15 women). The transcribed data were analysed using framework analysis.

Results

Eight themes relating to factors influencing health behaviour were identified: psychological legacy of pregnancy, relationships with healthcare professionals, physical impacts of pregnancy, social support and cultural norms, life‐scheduling, understanding and risk perception, appetite regulation, and prioritization of the baby. The women's recommendations for intervention components included addressing the emotional stress of pregnancy; conveying personalized risk in a motivational way, adopting a family‐centered approach, focusing on women's health rather than just the infant's, and developing flexible interventions. These recommendations were used to construct a model integrating the behaviour‐regulating factors with a suggested framework for intervention.

Conclusions

This study identified some common drivers that may regulate the health behaviours of women following GDM, and recognized some ways to improve care to impact on this. Interventions for diabetes prevention in this population need to address factors at both the individual and systemic levels.
Carbohydrate quantity in the dietary management of type 2 diabetes: A systematic review and meta‐analysis
Authors: Korsmo‐Haugen Henny‐Kristine , Brurberg Kjetil G. , Mann Jim , Aas Anne‐Marie
Published: August 2018

Aims

This systematic review and meta‐analysis (registration number: CRD42013005825) compares the effects of low carbohydrate diets (LCDs) on body weight, glycaemic control, lipid profile and blood pressure with the effects of higher carbohydrate diets (HCDs) in adults with type 2 diabetes.

Methods

MEDLINE, EMBASE, CENTRAL, CINAHL, Food Science Source and SweMed+ databases were systematically searched to identify randomized controlled trials (duration ≥3 months) investigating the effects of an LCD compared to an HCD in the management of type 2 diabetes. Data were extracted and pooled using a random effects model and were expressed as mean differences and risk ratio. Subgroup analyses were undertaken to examine the effects of duration of intervention, extent of carbohydrate restriction and risk of bias. The certainty of evidence was assessed using GRADE.

Results

Of the 1589 studies identified, 23, including 2178 participants, met inclusion criteria. Reductions were slightly greater with LCDs than with HCDs for HbA1c (−1.0 mmol/mol; CI, −1.9, −0.1 [−0.09%; CI, −0.17, −0.01]) and for triglycerides (−0.13 mmol/L; CI, −0.24, −0.02). Changes in weight, HDL‐ and LDL‐cholesterol, total cholesterol and blood pressure did not differ significantly between groups. Subgroup analyses suggested that the difference in HbA1c was evident only in studies with a duration of ≤6 months and with a high risk of bias.

Conclusions

The proportion of daily energy provided by carbohydrate intake is not an important determinant of response to dietary management, especially when considering longer term trials. A range of dietary patterns, including those traditional in Mediterranean countries, seems suitable for translating nutritional recommendations for individuals with diabetes into practical advice.
The effects of dietary supplementation with inulin and inulin‐propionate ester on hepatic steatosis in adults with non‐alcoholic fatty liver disease
Authors: Chambers Edward S. , Byrne Claire S. , Rugyendo Annette , Morrison Douglas J. , Preston Tom , Tedford Catriona , Bell Jimmy D. , Thomas Louise , Akbar Arne N. , Riddell Natalie E. , Sharma Rohini , Thursz Mark R. , Manousou Pinelopi , Frost Gary
Published: August 2018

The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non‐alcoholic fatty liver disease (NAFLD). Eighteen adults were randomized to receive 20 g/d of an inulin‐propionate ester (IPE), designed to deliver propionate to the colon, or an inulin control for 42 days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between the groups (P = 0.082), however, IHCL significantly increased within the inulin‐control group (20.9% ± 2.9% to 26.8% ± 3.9%; P = 0.012; n = 9), which was not observed within the IPE group (22.6% ± 6.9% to 23.5% ± 6.8%; P = 0.635; n = 9). The predominant SCFA from colonic fermentation of inulin is acetate, which, in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate‐mediated increase in IHCL.
Brain glucose uptake is associated with endogenous glucose production in obese patients before and after bariatric surgery and predicts metabolic outcome at follow‐up
Authors: Rebelos Eleni , Immonen Heidi , Bucci Marco , Hannukainen Jarna C. , Nummenmaa Lauri , Honka Miikka‐Juhani , Soinio Minna , Salminen Paulina , Ferrannini Ele , Iozzo Patricia , Nuutila Pirjo
Published: August 2018

Aims

To investigate further the finding that insulin enhances brain glucose uptake (BGU) in obese but not in lean people by combining BGU with measures of endogenous glucose production (EGP), and to explore the associations between insulin‐stimulated BGU and peripheral markers, such as metabolites and inflammatory markers.

Materials and methods

A total of 20 morbidly obese individuals and 12 lean controls were recruited from the larger randomized controlled SLEEVEPASS study. All participants were studied under fasting and euglycaemic hyperinsulinaemic conditions using fluorodeoxyglucose‐positron emission tomography. Obese participants were re‐evaluated 6 months after bariatric surgery and were followed‐up for ~3 years.

Results

In obese participants, we found a positive association between BGU and EGP during insulin stimulation. Across all participants, insulin‐stimulated BGU was associated positively with systemic inflammatory markers and plasma levels of leucine and phenylalanine. Six months after bariatric surgery, the obese participants had achieved significant weight loss. Although insulin‐stimulated BGU was decreased postoperatively, the association between BGU and EGP during insulin stimulation persisted. Moreover, high insulin‐stimulated BGU at baseline predicted smaller improvement in fasting plasma glucose at 2 and 3 years of follow‐up.

Conclusions

Our findings suggest the presence of a brain‐liver axis in morbidly obese individuals, which persists postoperatively. This axis might contribute to further deterioration of glucose homeostasis.
Dentists’ responses about the effectiveness of continuing education activities
Authors: Al‐Ansari Asim , Nazir Muhammad Ashraf
Published: August 2018

Objective

To report the responses of dentists about the effectiveness of continuing education (CE) activities.

Methods

This cross‐sectional study involved the administration of a pilot‐tested questionnaire amongst dentists from different cities of the eastern province of Saudi Arabia. A calculated sample of dentists (n = 323) was approached in person to collect their responses about CE activities they attended during the last one year. Descriptive statistics and multivariate logistic regression analyses were performed.

Results

The response rate was 79.5% as 257 dentists returned completed questionnaires. There were 54.9% male and 45.1% female participants (mean age 31.18 ± 12.4 years). The majority of participants reported an improvement in knowledge (79.8%), a motivation for learning (79.8%), and quality of dental care (73.9%) as a result of CE activities. More than two‐thirds recognised the importance of CE courses for maintaining licensure in dentistry, and 91.1% felt the need to increase CE activities. Logistic regression models showed that male participants were less likely (OR = 0.48, P = 0.05) than female counterparts to report an improvement in clinical skills. Having a private job (OR = 2.38 P = 0.005) and >10 years since graduation (OR = 1.84, P = 0.05) were associated with an improvement in clinical skills. Believing in the importance of CE activities for maintaining licensure was significantly associated with the effectiveness of CE activities in improving knowledge (OR = 2.76, P = 0.01), clinical skills (OR = 2.02, P = 0.04) and patient satisfaction (OR = 2.22, P = 0.01).

Conclusion

The majority of dentists recognised that CE activities were effective in improving their knowledge, clinical practice, quality of patient care and motivation for learning.
Self‐perceived preparedness of final year dental students in a developing country—A multi‐institution study
Authors: Ali Kamran , Cockerill Josephine , Zahra Daniel , Qazi Haroon S , Raja Ulfat , Ataullah Khurram
Published: August 2018

Aims

To evaluate the self‐perceived preparedness to practice of final year dental undergraduate students in three dental institutions.

Methods

Dental undergraduate students in their final year from three dental institutions in Pakistan were invited to participate in an online study to assess self‐perceived preparedness using a validated preparedness assessment scale.

Results

In total, 134 students responded to the questionnaire yielding a response rate of 72%. Students felt adequately prepared to carry out several clinical procedures including clinical assessment, fillings, tooth extractions and communication skills. However, perceived preparedness was low in the students’ ability to undertake intraoral radiographs, treatment planning, crowns, multirooted endodontics, research skills, referral for suspected oral cancer and raising concerns regarding inappropriate behaviour of colleagues.

Conclusions

This is the first study which investigates the self‐perceived preparedness of final year undergraduate dental students in Pakistan. The results show that the self‐perceived preparedness of final year students was satisfactory for a range of clinical and affective skills. However, several areas of weaknesses were identified which underscore the need for additional training and consolidation.
Outcomes of decades long installation of nest boxes for arboreal mammals in southern Australia
Authors: Goldingay Ross L. , Thomas Karen J. , Shanty Devi
Published: August 2018

Nest boxes are commonly installed to support hollow‐using species where the abundance of hollow‐bearing trees is deficient. Recent studies have provided equivocal evidence about the effectiveness of nest box projects and have highlighted significant management costs associated with some projects. We document the functionality of 303 nest boxes installed across five different community‐led projects in southern Australia for periods of 10–25 years. As expected, we found that nest boxes lost functionality over time. However, 60% remained functional to support the Brush‐tailed Phascogale (Phascogale tapoatafa) and the Sugar Glider (Petaurus breviceps) after almost 20 years. Years installed, method of nest box attachment and tree species influenced whether boxes remained functional. Nest box construction material changed over time so could not be assessed specifically. When inspected in a single year, the Brush‐tailed Phascogale occupied 9% of functional boxes and another 48% contained their nests. The Sugar Glider occupied 15% of functional boxes and another 22% contained their nests. These values suggest the nest box installations were highly effective for these species, although more detailed study is needed to understand what contribution these installations have made to support the local populations. Maintenance of most nest boxes occurred twice a year in the first five years after installation, but many received no maintenance for periods of three years, and some 10–15 years, before our census. Our findings suggest that infrequent maintenance by community groups can sustain nest box projects over periods of several decades. Research into employing nest boxes as a management tool in Australia is still in its infancy. Further studies are needed to resolve factors that limit their effectiveness.
Prevalence and phenotype of the c.1529C>T SPG7 variant in adult‐onset cerebellar ataxia in Italy
Authors: Mancini C. , Giorgio E. , Rubegni A. , Pradotto L. , Bagnoli S. , Rubino E. , Prontera P. , Cavalieri S. , Di Gregorio E. , Ferrero M. , Pozzi E. , Riberi E. , Ferrero P. , Nigro P. , Mauro A. , Zibetti M. , Tessa A. , Barghigiani M. , Antenora A. , Sirchia F. , Piacentini S. , Silvestri G. , De Michele G. , Filla A. , Orsi L. , Santorelli F. M. , Brusco A.
Published: August 2018

Background and purpose

Hereditary ataxias are heterogeneous groups of neurodegenerative disorders, characterized by cerebellar syndromes associated with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive impairment.

Recent reports have suggested mutations in the SPG7 gene, causing the most common form of autosomal recessive spastic paraplegia (MIM#607259), as a main cause of ataxias. The majority of described patients were homozygotes or compound heterozygotes for the c.1529C>T (p.Ala510Val) change. We screened a cohort of 895 Italian patients with ataxia for p.Ala510Val in order to define the prevalence and genotype–phenotype correlation of this variant.

Methods

We set up a rapid assay for c.1529C>T using restriction enzyme analysis after polymerase chain reaction amplification. We confirmed the diagnosis with Sanger sequencing.

Results

We identified eight homozygotes and 13 compound heterozygotes, including two novel variants affecting splicing.

Mutated patients showed a pure cerebellar ataxia at onset, evolving in mild spastic ataxia (alternatively) associated with dysarthria (~80% of patients), urinary urgency (~30%) and pyramidal signs (~70%). Comparing homozygotes and compound heterozygotes, we noted a difference in age at onset and Scale for the Assessment and Rating of Ataxia score between the two groups, supporting an earlier and more severe phenotype in compound heterozygotes versus homozygotes.

Conclusions

The SPG7 c.1529C>T (p.Ala510Val) mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late‐onset pure ataxia. Moreover, the heterozygous/homozygous genotype appeared to predict the onset of clinical manifestation and disease progression.
Deep learning applied to whole‐brain connectome to determine seizure control after epilepsy surgery
Authors: Gleichgerrcht Ezequiel , Munsell Brent , Bhatia Sonal , Vandergrift William A. , Rorden Chris , McDonald Carrie , Edwards Jonathan , Kuzniecky Ruben , Bonilha Leonardo
Published: August 2018

Objective

We evaluated whether deep learning applied to whole‐brain presurgical structural connectomes could be used to predict postoperative seizure outcome more accurately than inference from clinical variables in patients with mesial temporal lobe epilepsy (TLE).

Methods

Fifty patients with unilateral TLE were classified either as having persistent disabling seizures (SZ) or becoming seizure‐free (SZF) at least 1 year after epilepsy surgery. Their presurgical structural connectomes were reconstructed from whole‐brain diffusion tensor imaging. A deep network was trained based on connectome data to classify seizure outcome using 5‐fold cross‐validation.

Results

Classification accuracy of our trained neural network showed positive predictive value (PPV; seizure freedom) of 88 ± 7% and mean negative predictive value (NPV; seizure refractoriness) of 79 ± 8%. Conversely, a classification model based on clinical variables alone yielded <50% accuracy. The specific features that contributed to high accuracy classification of the neural network were located not only in the ipsilateral temporal and extratemporal regions, but also in the contralateral hemisphere.

Significance

Deep learning demonstrated to be a powerful statistical approach capable of isolating abnormal individualized patterns from complex datasets to provide a highly accurate prediction of seizure outcomes after surgery. Features involved in this predictive model were both ipsilateral and contralateral to the clinical foci and spanned across limbic and extralimbic networks.
Everolimus in infants with tuberous sclerosis complex–related West syndrome: First results from a single‐center prospective observational study
Authors: Samueli Sharon , Dressler Anastasia , Gröppel Gudrun , Scholl Theresa , Feucht Martha
Published: August 2018

Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS). Currently available treatment options are ineffective in the majority of affected infants and/or associated with potential serious side effects. Based on the assumption that mTOR overactivation results in increased neuroexcitability in TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result, everolimus recently received approval for the adjunctive treatment of patients aged ≥2 years with refractory TSC‐associated focal and secondary generalized seizures. However, efficacy and safety data for infants with TSC‐associated WS are still lacking. Therefore, a prospective open‐label observational study was initiated at our center, to evaluate everolimus add‐on treatment in infants with TSC‐associated WS, previously refractory to standard treatment. For this preliminary report, data from four male infants with TSC2 and a median observation period of 13 (range = 8‐42) months after treatment initiation were analyzed. Two infants showed electroclinical remission until day 14 after everolimus treatment initiation. In one additional infant, hypsarrhythmia resolved. No relapse after initial response was documented. Developmental progress improved in three infants. Tolerability was similar to that described in older children. According to our preliminary results, everolimus appears to have the potential to treat successfully both spasms and hypsarrhythmia in infants with TSC‐associated WS, contributing to better developmental progress.
Return of individual results in epilepsy genomic research: A view from the field
Authors: Ottman Ruth , Freyer Catharine , Mefford Heather C. , Poduri Annapurna , Lowenstein Daniel H. ,   Epilepsy Return of Results Workshop Participants
Published: August 2018

Genomic findings are emerging rapidly in 2 large, closely related epilepsy research consortia: the Epilepsy Phenome/Genome Project and Epi4K. Disclosure of individual results to participants in genomic research is increasingly viewed as an ethical obligation, but strategies for return of results were not included in the design of these consortia, raising complexities in establishing criteria for which results to offer, determining participant preferences, managing the large number of sites involved, and covering associated costs. Here, we describe the challenges faced, alternative approaches considered, and progress to date. Experience from these 2 consortia illustrates the importance, for genomic research in epilepsy and other disorders, of including a specific plan for return of results in the study design, with financial support for obtaining clinical confirmation and providing ongoing support for participants. Participant preferences for return of results should be established at the time of enrollment, and methods for allowing future contacts with participants should be included. In addition, methods should be developed for summarizing meaningful, comprehensible information about findings in the aggregate that participants can access in an ongoing way.
Deleterious alleles in the context of domestication, inbreeding, and selection
Authors: Bosse Mirte , Megens Hendrik‐Jan , Derks Martijn F. L. , de Cara Ángeles M. R. , Groenen Martien A. M.
Published: August 2018

Each individual has a certain number of harmful mutations in its genome. These mutations can lower the fitness of the individual carrying them, dependent on their dominance and selection coefficient. Effective population size, selection, and admixture are known to affect the occurrence of such mutations in a population. The relative roles of demography and selection are a key in understanding the process of adaptation. These are factors that are potentially influenced and confounded in domestic animals. Here, we hypothesize that the series of events of bottlenecks, introgression, and strong artificial selection associated with domestication increased mutational load in domestic species. Yet, mutational load is hard to quantify, so there are very few studies available revealing the relevance of evolutionary processes. The precise role of artificial selection, bottlenecks, and introgression in further increasing the load of deleterious variants in animals in breeding and conservation programmes remains unclear. In this paper, we review the effects of domestication and selection on mutational load in domestic species. Moreover, we test some hypotheses on higher mutational load due to domestication and selective sweeps using sequence data from commercial pig and chicken lines. Overall, we argue that domestication by itself is not a prerequisite for genetic erosion, indicating that fitness potential does not need to decline. Rather, mutational load in domestic species can be influenced by many factors, but consistent or strong trends are not yet clear. However, methods emerging from molecular genetics allow discrimination of hypotheses about the determinants of mutational load, such as effective population size, inbreeding, and selection, in domestic systems. These findings make us rethink the effect of our current breeding schemes on fitness of populations.
Ethylenediaminetetraacetic acid (EDTA) anticoagulant affects the refractometric measurement of total protein concentration in equine synovial fluid
Authors: Hann M. J. , Parker R. A. , South V. E. N. , Underwood C. E.
Published: August 2018

The objectives of this study were to (i) determine the effect of ethylenediaminetetraacetic acid (EDTA) concentration on the refractometric measurement of the total protein (TP) concentration of equine synovial fluid and (ii) assess the effect of time and temperature on the refractometric measurement of TP concentration. Synovial fluid was retrieved aseptically from horses presenting to Liphook Equine Hospital either (a) immediately after euthanasia or (b) from those requiring arthrocentesis as part of their clinical investigation. Samples were aliquoted into commercially available (i) plain tubes (0.5 mL; control) and (ii) EDTA tubes (at different volumes to obtain serial dilutions of EDTA:synovial fluid). TP concentration was measured by two independent observers using a calibrated hand‐held refractometer. Samples from a separate group of horses were stored for 24 h at 4°C and 20°C before analysis to assess the effects of time and temperature. Results were compared using repeated measures ANOVA. TP concentration was significantly higher at all EDTA concentrations compared to control samples, with the greatest effect seen with higher concentrations (P<0.0001 for samples with ≥3.17 mg EDTA/mL). Storage time or temperature did not significantly affect TP concentration. Refractometric measurement of small volumes of synovial fluid in commercially available EDTA tubes leads to artificially elevated TP concentrations. Delays in sample analysis and alterations in storage conditions did not significantly affect TP concentration within the parameters studied. The magnitude of overestimation of synovial total protein concentration could result in misclassification of suspect synovial sepsis cases where EDTA tubes are used.
Risk of diabetes with fibrates and statins: a pharmacoepidemiological study in VigiBase®
Authors: Montastruc François , Benevent Justine , Rousseau Vanessa , Durrieu Geneviève , Sommet Agnès , Montastruc Jean‐Louis
Published: August 2018

In contrast to statins, the risk of diabetes with fibrates was not clearly studied. This study investigates a putative signal of diabetes associated with the use of fibrates using the World Health Organization (WHO) global individual case safety reports database, VigiBase®. We included all reports registered until the 31st December 2017 in VigiBase® to measure the risk of reporting ‘hyperglycemia or new onset of diabetes’ (SMQ term) compared with all other reports [as a reporting odds ratio (ROR 95% CI)] for fibrates, statins, and the combination fibrates + statins. The likelihood that diabetes resulted from statin–fibrate interaction was also estimated. According to the interaction additive model, a ROR value for coexposure exceeding the sum of the RORs estimated for each individual class of drug supports a potential drug–drug interaction (DDI). To assess the stability of our results, we performed several sensitivity analyses, according to outcome definition and after exclusion of putative competitive (hyperglycemic) drugs. We included 19 149 patients exposed to fibrates (without statins), 177 323 to statins (without fibrates) and 3 247 to statins plus fibrates. In contrast to statins (ROR = 1.75, 95% CI 1.72–1.78), no association was found for fibrates (ROR = 0.76, 95% CI 0.71–0.82). The ROR value was lower for the combination statins plus fibrates (ROR = 1.46, 95% CI 1.28–1.67). Similar trends were found in sensitivity analyses. This study, performed in the real conditions of use, failed to find a signal of diabetes with fibrates. It strengths the association previously described with statin without any evidence for a statin–fibrate DDI.
NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells
Authors: Becker‐Kettern Julia , Paczia Nicole , Conrotte Jean‐François , Zhu Chenchen , Fiehn Oliver , Jung Paul P. , Steinmetz Lars M. , Linster Carole L.
Published: August 2018

NADHX and NADPHX are hydrated and redox inactive forms of the NADH and NADPH cofactors, known to inhibit several dehydrogenases in vitro. A metabolite repair system that is conserved in all domains of life and that comprises the two enzymes NAD(P)HX dehydratase and NAD(P)HX epimerase, allows reconversion of both the S‐ and R‐epimers of NADHX and NADPHX to the normal cofactors. An inherited deficiency in this system has recently been shown to cause severe neurometabolic disease in children. Although evidence for the presence of NAD(P)HX has been obtained in plant and human cells, little is known about the mechanism of formation of these derivatives in vivo and their potential effects on cell metabolism. Here, we show that NAD(P)HX dehydratase deficiency in yeast leads to an important, temperature‐dependent NADHX accumulation in quiescent cells with a concomitant depletion of intracellular NAD+ and serine pools. We demonstrate that NADHX potently inhibits the first step of the serine synthesis pathway in yeast. Human cells deficient in the NAD(P)HX dehydratase also accumulated NADHX and showed decreased viability. In addition, those cells consumed more glucose and produced more lactate, potentially indicating impaired mitochondrial function. Our results provide first insights into how NADHX accumulation affects cellular functions and pave the way for a better understanding of the mechanism(s) underlying the rapid and severe neurodegeneration leading to early death in NADHX repair‐deficient children.
Trade union pedagogy and cross‐border action
Authors: NIFOROU CHRISTINA , HODDER ANDY
Published: August 2018

In this article, we examine the potential of global union pedagogy to address the structural and political challenges of cross‐border trade‐union action. We do so by proposing an analytical framework that draws on labour relations, political sociology and education to explain educational processes and outcomes as responses to the pitfalls of global labour campaigns and the inadequacy of global and local labour institutions. We proceed to assess the value of our framework by elaborating on its different dimensions – framing, synthesizing, connecting and regenerating – in relation to the educational work of a global union federation, namely the International Transport Workers' Federation. We find that an actor‐centred approach that combines top–down, bottom–up as and horizontal processes of collecting knowledge from different contexts and making links between different countries, industries and parts of supply chains can help actors realize that their seemingly diverse concerns are essentially different manifestations of the same problem.
German seafarers, anti‐fascism and the anti‐Stalinist left: the ‘Antwerp Group’ and Edo Fimmen's International Transport Workers' Federation, 1933–40
Authors: HYSLOP JONATHAN
Published: August 2018

Between the mid‐1930s and the beginning of the Second World War, a group of German seamen based in Antwerp combined with Amsterdam‐based Edo Fimmen, secretary of the International Transport Workers' Federation, to wage a campaign against the Nazi government among the sailors of the German merchant fleet. They organized cells of supporters on German ships, encouraged informal resistance, circulated propaganda and planned sabotage. The Antwerp Group was a breakaway from the Comintern‐aligned International of Seafarers and Harbour Workers (ISH). The Antwerp men were reacting against the ineffectiveness of the response of the German communist leadership to Hitler's takeover of power, and against the growing subordination of the ISH to Soviet interests. By highlighting the role of anti‐Stalinist militants in the anti‐fascism of the 1930s, the article contributes to the recent scholarship on anti‐fascism – a scholarship that has tended to emphasize the transnationalism and ideological diversity of anti‐fascism, rather than seeing it in national terms, or as a monolithic entity controlled by Moscow.
Histone H3K36M mutation and trimethylation patterns in chondroblastoma
Authors: Lu Chuanyong , Ramirez Daniel , Hwang Sinchun , Jungbluth Achim , Frosina Denise , Ntiamoah Peter , Healey John , Zhu Guo , Chen Wen , Klein Michael , Hameed Meera
Published: August 2018

Aims

Histones are essential components of chromatin, and mutations in histones lead to alterations in methylation and acetylation, which play an important role in tumorigenesis. Most of the chondroblastomas harbour the H3K36M mutation. With the availability of a mutation‐specific antibody, we sought to assess the sensitivity of this antibody and the alterations of histone methylation in a series of chondroblastoma cases.

Methods and results

Immunohistochemical staining with antibodies against H3K36M, trimethylated histones (H3K27me3 and H3K36me3) and an osteoblastic marker (SATB2) was performed on 27 chondroblastomas from 27 patients. The clinical and radiological characteristics of each patient were reviewed. All 27 tumours showed typical radiological and histological features of chondroblastoma, with a subset of cases showing secondary aneurysmal bone cyst changes (11/27), giant‐cell‐rich foci (4/27), and matrix‐rich areas mimicking chondromyxoid fibroma (1/27). All except one case (26/27, 96%) showed positive H3K36M immunostaining (nuclear). In the majority of cases, there was a diffuse staining pattern. Immunohistochemical staining for H3K27me3 and H3K36me3 showed a heterogeneous staining pattern in all cases, regardless of mutation status. None of the cases showed loss of positivity or diffuse positivity. Focal or diffuse SATB2 expression was seen in 21 of 26 tumours (81%).

Conclusion

Our results demonstrate that the vast majority of chondroblastomas are positive for H3K36M by immunohistochemical analysis, confirming its diagnostic value. H3K27me3 expression and H3K36me3 expression are heterogeneous in these tumours.
Electrical properties of Y/Mg modified NiO simple oxides for negative temperature coefficient thermistors
Authors: He Zhenli , Li Zhicheng , Xiang Qinghua , Yan Weiqin , Zhang Hong
Published: August 2018

The semiconductors based on simple oxide have unique features with controllable electrical property by element doping. Y3+ doped NiO (Ni1−xYxO, x ≤ 0.01) and Mg2+ substituted Ni0.995Y0.005O (Ni0.995−yY0.005MgyO, y ≤ 0.5) powders were synthesized by a wet chemical method. The related ceramics were obtained by conventional ceramic processing. Phase component, microstructure, electrical property and temperature sensitivity of the prepared ceramics were investigated. All ceramics have a rock‐salt type crystalline structure. The room‐temperature resistivity of the ceramics can be widely adjusted from 254 to 12 322 Ω·cm by changing the concentrations of Y3+ and Mg2+ ions. The samples show typical characteristics of negative temperature coefficient of resistivity and have high temperature sensitivity with material constants higher than 4745 K. The analysis of impedance spectra indicates that the electrical properties resulted from both grain effect and grain boundary effect. Both band conduction and small polaron hopping were proposed as possible conduction mechanisms in the studied ceramics.
Investigating photocatalytic property of TiO2 nanorods fabricated hydrothermally at equal molar ratio of KOH and NaOH
Authors: Naseri Katayoon , Allahverdi Ali
Published: August 2018

TiO2 photocatalysts were prepared by hydrothermal method at temperatures of 110, 155, and 200°C for 24 hours, using KOH (5 mol/L):NaOH (5 mol/L) solution and anatase TiO2 powder with an average particle size of 0.13 μm as precursor and by calcining at two different temperatures of 450 and 700°C. An overall photocatalytic removal efficiency of 93% was achieved for Rhodamine B dye under UV light irradiation by the photocatalyst obtained at synthesis and calcination temperatures of 155 and 700°C, respectively, which indicated a nanorod morphology with a mean diameter of about 34 nm.
Interleukin‐33 contributes to disease severity in Dengue virus infection in mice
Authors: Marques Rafael E. , Besnard Anne‐Gaëlle , Maillet Isabelle , Fagundes Caio T. , Souza Danielle G. , Ryffel Bernhard , Teixeira Mauro M. , Liew Foo Y. , Guabiraba Rodrigo
Published: August 2018

The excessive inflammation often present in patients with severe dengue infection is considered both a hallmark of disease and a target for potential treatments. Interleukin‐33 (IL‐33) is a pleiotropic cytokine with pro‐inflammatory effects whose role in dengue has not been fully elucidated. We demonstrate that IL‐33 plays a disease‐exacerbating role during experimental dengue infection in immunocompetent mice. Mice infected with dengue virus serotype 2 (DENV2) produced high levels of IL‐33. DENV2‐infected mice treated with recombinant IL‐33 developed markedly more severe disease compared with untreated mice as assessed by mortality, granulocytosis, liver damage and pro‐inflammatory cytokine production. Conversely, ST2−/− mice (deficient in IL‐33 receptor) infected with DENV2 developed significantly less severe disease compared with wild‐type mice. Furthermore, the increased disease severity and the accompanying pathology induced by IL‐33 during dengue infection were reversed by the simultaneous treatment with a CXCR2 receptor antagonist (DF2156A). Together, these results indicate that IL‐33 plays a disease‐exacerbating role in experimental dengue infection, probably driven by CXCR2‐expressing cells, leading to elevated pro‐inflammatory response‐mediated pathology. Our results also indicate that IL‐33 is a potential therapeutic target for dengue infection.
The inflammasomes, immune guardians at defence barriers
Authors: Palazon‐Riquelme Pablo , Lopez‐Castejon Gloria
Published: August 2018

As a result of its strategic location, the epithelium is constantly exposed to a wide variety of pathogen and danger signals. Traditionally, the epithelium has been perceived as a defensive but passive barrier; however, it has now become evident that the epithelium senses and actively responds to these signals in order to maintain barrier homeostasis and contributes to the inflammatory response. One way it does this is by producing pro‐inflammatory cytokines including interleukin‐1β (IL‐1β) and IL‐18. These two cytokines are synthesized as inactive precursors, the maturation of which is mediated by pro‐inflammatory caspases after the activation and assembly of macromolecular complexes called inflammasomes. Epithelial cells express a large panel of inflammasome components, and although the molecular mechanisms underlying the activation of these complexes in haematopoietic cells are well understood, how epithelial cells react to danger signals to activate the inflammasome remains unclear. We review and discuss how different inflammasomes contribute to barrier homeostasis and inflammation at several barrier sites, their mechanisms and how their aberrant regulation contributes to disease at the different epithelia.
YY1 binds to the E3ʹ enhancer and inhibits the expression of the immunoglobulin κ gene via epigenetic modifications
Authors: Zhou Xiaorong , Xian Weiwei , Zhang Jie , Zhu Yiqing , Shao Xiaoyi , Han Yu , Qi Yue , Ding Xiaoling , Wang Xiaoying
Published: August 2018

The rearrangement and expression of immunoglobulin genes are regulated by enhancers and their binding transcriptional factors that activate or suppress the activities of the enhancers. The immunoglobulin κ (Igκ) gene locus has three important enhancers: the intrinsic enhancer (Ei), 3′ enhancer (E3′), and distal enhancer (Ed). Ei and E3′ are both required for Igκ gene rearrangement during early stages of B‐cell development, whereas optimal expression of the rearranged Igκ gene relies on both E3′ and Ed. The transcription factor YY1 affects the expression of many genes involved in B‐cell development, probably by mediating interactions between their enhancers and promoters. Herein, we found that YY1 binds to the E3ʹ enhancer and suppresses Igκ expression in B lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1 enhanced Igκ expression, which was associated with increased levels of E2A (encoded by the TCF3 gene) and its binding to the E3ʹ enhancer. Moreover, in germinal centre B cells and plasma cells, YY1 expression was reversely associated with Igκ levels, implying that YY1 might facilitate antibody affinity maturation in germinal centre B cells through the transient attenuation of Igκ expression.
The impact of inflationary cytomegalovirus‐specific memory T cells on anti‐tumour immune responses in patients with cancer
Authors: Luo Xiao‐Hua , Meng Qingda , Rao Martin , Liu Zhenjiang , Paraschoudi Georgia , Dodoo Ernest , Maeurer Markus
Published: August 2018

Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen‐specific CD8+ T‐cell pools with an effector‐memory phenotype and enrichment of these immune cells in peripheral organs. We review here this ‘memory T‐cell inflation’ phenomenon and associated factors including age and sex. ‘Collateral damage’ due to CMV‐directed immune reactivity may occur in later stages of life – arising from CMV‐specific immune responses that were beneficial in earlier life. CMV may be considered an age‐dependent immunomodulator and a double‐edged sword in editing anti‐tumour immune responses. Emerging evidence suggests that CMV is highly prevalent in patients with a variety of cancers, particularly glioblastoma. A better understanding of CMV‐associated immune responses and its implications for immune senescence, especially in patients with cancer, may aid in the design of more clinically relevant and tailored, personalized treatment regimens. ‘Memory T‐cell inflation’ could be applied in vaccine development strategies to enrich for immune reactivity where long‐term immunological memory is needed, e.g. in long‐term immune memory formation directed against transformed cells.
Climate risk on two vegetation axes—Tropical wet‐to‐dry and temperate arid‐to‐moist forests
Authors: Williams John N. , Rivera Raul , Choe Hyeyeong , Schwartz Mark W. , Thorne James H.
Published: August 2018

Aim

Assess climatic risk to vegetation types associated with tropical and temperate ecosystems based on exposure analysis, which models future risk as a function of deviation from current climate variable distributions.

Location

Oaxaca State, Mexico.

Taxon

Broadly defined vegetation types used in state‐ and national‐level vegetation classification systems. These types can be grouped into series representing dry‐to‐wet conditions for tropical and temperate vegetation.

Methods

We used climate exposure analysis to compare current and future climate parameters for the major vegetation types of Oaxaca. This technique integrates a recent vegetation map with historical climate data (1981–2010) to produce a baseline climate layer that is compared to climate projections made with five different global circulation models for near‐future (2015–2039) and end‐century (2075–2099) periods using two emissions scenarios (RCP4.5 and 8.5). We classified the frequency distribution of the baseline climate into five exposure classes where the closer values are to mean climate conditions, the lower the exposure. Future exposure was estimated by classifying the vegetation pixels into the same exposure classes, now based on future climate values. Increased exposure risk was assessed based on the fraction of pixels that moved into higher exposure classes from one period to another.

Results and main conclusions

Our analysis showed four general trends: (a) the higher, current track emissions scenario produced much larger end‐century climate exposure; (b) for the tropical vegetation series, tropical evergreen forests are projected as most exposed by end‐century; (c) for the temperate vegetation series the matorral‐shrubland and conifer forests are the most impacted; and (d) the fiveGCMs considered showed some convergence in their end‐century climate exposure predictions, with coastal and low‐elevation areas of the State projected to experience the greatest exposure, and the interior mountain slopes and central region projected to experience the least exposure and be the most climatically stable.
An ancient and a recent colonization of islands by an Australian sap‐feeding insect
Authors: Fromont Caroline , Rymer Paul D. , Riegler Markus , Cook James M.
Published: August 2018

Aim

To assess the genetic structure, biogeography, and the potential for speciation, of a highly host‐specific insect pest with mainland and island populations.

Location

East coast of Australia, Lord Howe Island (LHI), and New Zealand.

Methods

We focussed on Mycopsylla fici, a plant sap‐feeding insect host‐specific to the fig tree Ficus macrophylla. We genotyped 152 insects from across the natural and extended host plant range at 14 microsatellite loci and analysed the data using standard population genetics statistics, Discriminant Analysis of Principal Components, genetic autocorrelation, and two Bayesian clustering approaches.

Results

Genetic analyses revealed that the northeastern Australian mainland population (Brisbane) is the centre of genetic diversity. Northeastern and southeastern (Sydney) mainland populations are genetically differentiated and interconnected in a stepping‐stone pattern. The LHI population is the most distinct genetically and Bayesian estimates indicated that the most recent colonization occurred c. 2,000‐17,500 years ago from a northeastern mainland origin. In contrast, the New Zealand population is little differentiated from the Sydney population and probably diverged by colonization within the past 200 years.

Main conclusions

The strong differentiation in nuclear microsatellites mirrors previous evidence for divergence of the LHI population from both mtDNA and endosymbiont DNA. The LHI population may be undergoing speciation from the mainland populations, with an oceanic barrier to gene flow. In contrast, the geographically isolated population in Auckland represents a far more recent colonization reflecting the contemporary naturalization of the plant host in New Zealand.