bluuebunny/crossref_metadata_2025 huggingface dataset:
Exceptional preservation of a Late Cretaceous dinosaur nesting site from Mongolia reveals colonial nesting behavior in a non-avian theropod
Authors: Tanaka Kohei , Kobayashi Yoshitsugu , Zelenitsky Darla K. , Therrien François , Lee Yuong-Nam , Barsbold Rinchen , Kubota Katsuhiro , Lee Hang-Jae , Chinzorig Tsogtbaatar , Idersaikhan Damdinsuren
Published: July 2019

Colonial nesting behavior has been inferred in a variety of non-avian dinosaurs based on high concentrations of nests preserved in an area, but sedimentologic and taphonomic evidence demonstrating the contemporaneity of the nests is often lacking. A new nesting site discovered in the Upper Cretaceous Javkhlant Formation of the eastern Gobi Desert, Mongolia, preserves at least 15 egg clutches laid by a probable non-avian theropod, and provides strong evidence for colonial nesting in a non-avian dinosaur. The occurrence of the clutches at the top of a common paleosurface, the distribution of eggshell fragments within clutches, the presence of a consistent two-layer sediment infill within eggs, and a thin marker lithologic unit blanketing all the clutches indicate the clutches were laid and hatched in a single nesting season. Despite the absence of sedimentologic evidence indicative of nest structure, statistical analyses of egg characteristics and facies association reveal the clutches were likely incubated in covered or buried nests. Based on the number of hatched clutches, the hatching success rate of the colony was high (60%), similar to that of extant crocodylian populations and bird species that attend and/or protect their nests during the incubation period, which indicates nest attendance behavior in the Javkhlant theropods. Thus, colonial nesting with parental attendance, widespread in extant birds, likely evolved initially among non-brooding, non-avian dinosaurs to increase nesting success.
Physical modelling of the response of reef islands to sea-level rise
Authors: Tuck Megan E. , Kench Paul S. , Ford Murray R. , Masselink Gerd
Published: July 2019

Sea-level rise and increased storminess are expected to destabilize low-lying reef islands formed on coral reef platforms, and increased flooding is expected to render them uninhabitable within the coming decades. Such projections are founded on the assumption that islands are geologically static landforms that will simply drown as sea-level rises. Here, we present evidence from physical model experiments of a reef island that demonstrates islands have the capability to morphodynamically respond to rising sea level through island accretion. Challenging outputs from existing models based on the assumption that islands are geomorphologically inert, results demonstrate that islands not only move laterally on reef platforms, but overwash processes provide a mechanism to build and maintain the freeboard of islands above sea level. Implications of island building are profound, as it will offset existing scenarios of dramatic increases in island flooding. Future predictive models must include the morphodynamic behavior of islands to better resolve flood impacts and future island vulnerability.
Fifteen-minute consultation: Initial management of suspected acute leukaemia by non-specialists
Authors: Behjati Sam , Ruffle Amy , Kelly Anne , Dickens Emmy
Published: July 2019

Leukaemia is the most common cancer of childhood. Most children with a new diagnosis of leukaemia are clinically stable at initial presentation. However, there are a number of life-threatening complications that have to be considered and monitored for. These complications include sepsis, tumour lysis syndrome, mediastinal masses, bleeding and pain. The aim of this article is to equip the general paediatrician with a framework for managing children with suspected leukaemia, prior to transfer to the primary treatment centre. The presentation, diagnosis and definitive treatment of acute leukaemia is not in the remit of this article.
The effect of resveratrol supplementation on the expression levels of factors associated with cellular senescence and sCD163/sTWEAK ratio in patients with type 2 diabetes mellitus: study protocol for a double-blind controlled randomised clinical trial
Authors: Abdollahi Shima , Salehi-Abargouei Amin , Tabatabaie Mahtab , Sheikhha Mohammad Hasan , Fallahzadeh Hossein , Rahmanian Masoud , Toupchian Omid , Karimi-Nazari Elham , Mozaffari-Khosravi Hassan
Published: July 2019

Introduction

Over the past decades, the number of people with type 2 diabetes (T2D) has increased globally. One of the major complications in these patients is cardiovascular disease; it seems that the cell proliferation inhibition can improve vascular function in these patients. It is proposed that peroxisome proliferator-activated receptor alpha (PPARα) can induce cell cycle arrest via cyclin-dependent kinase inhibitor 2A (p16) activation. Also, it has been shown that phosphorylated tumour suppressor protein p53 is involved in cell senescence by cyclin-dependent kinase inhibitor 1 (p21) upregulation. Resveratrol is a natural polyphenol and appears to improve the vascular function through the mentioned pathways. We will aim to evaluate the effects of resveratrol supplementation on mRNA expression of PPARα, p53, p21 and p16 in patients with T2D. We will also measure serum levels of cluster of differentiation 163 (CD163) and tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) as the indicators of cardiovascular status.

Methods and analysis

Seventy-two subjects suffering from T2D will participate in this double-blind randomised parallel placebo-controlled clinical trial. Participants will be randomly assigned to receive 1000 mg/day trans-resveratrol or placebo (methyl cellulose) for 8 weeks. The mRNA expression levels of PPARα, p53, p21 and p16 genes will be assessed using real-time PCR and serum CD163 and TWEAK levels will be measured using commercially available ELISA kits at baseline and the end of the study. Clinical outcome parameters (glycaemic and lipid profiles and body composition) will also be measured before and after study duration.

Ethics and dissemination

The study is performed in agreement with the Declaration of Helsinki and is approved by the Ethics Committee of the Shahid Sadoughi University of Medical Sciences (no: ir.ssu.sph.rec.1396.120). The results will be published in scientific journals.

Trial registration number

IRCT20171118037528N1; Pre-results.
Do emissions from landfill fires affect pregnancy outcomes? A retrospective study after arson at a solid waste facility in Sicily
Authors: Mazzucco Walter , Tavormina Elisa , Macaluso Maurizio , Marotta Claudia , Cusimano Rosanna , Alba Davide , Costantino Claudio , Grammauta Rosario , Cernigliaro Achille , Scondotto Salvatore , Vitale Francesco
Published: July 2019

Objectives

In response to public health concern about effects of arson at solid waste management plants in July 2012, we analysed vital statistics data to evaluate any potential effect on pregnancies at different gestational ages of pollutants emitted from the landfill on fire.

Setting

A community living near the largest landfill plant in Sicily.

Participants

The study group comprised 551 births, live births and stillbirths from pregnancies of mothers residing in the extra-urban exposed area, conceived during a 40 week period during which the highest fire’s peak might have influenced pregnancy.

Primary and secondary outcome measures

Birth outcomes (gestational age <37 and <32 weeks, low birth weight, very low birth weight and small for gestational age) in the study group were compared with the ones of a reference group of women residing in areas of Sicily with similarly low population density and industrial development.

Results

Among singleton live births we observed a three-fold increase in risk of very preterm birth between the extra-urban area and the remaining low inhabitants density and unindustrialised areas for births whose pregnancies were in the third trimester (OR adjusted for maternal age and infant gender=3.41; 95% CI 1.04 to 11.16). There was an excess of very low birth weight singleton infants in the study group as compared with the reference group, which was limited to births to mothers exposed during periconception period (OR adjusted for maternal age and infant gender=4.64; 95% CI 1.04 to 20.6) and first trimester (OR adjusted for maternal age and infant gender=3.66; 95% CI 1.11 to 12.1). The association estimates were imprecise due to the small number of outcomes recorded.

Conclusions

The study documented an excess of very preterm and very low birth weight among infants born to mothers exposed to the landfill fire emissions during conception or early pregnancy.
Clinical trial protocol of doublet therapy and olanzapine for carboplatin-induced nausea and vomiting in patients with thoracic cancer: a multicentre phase II trial
Authors: Iihara Hirotoshi , Shimokawa Mototsugu , Gomyo Takenobu , Fujita Yukiyoshi , Yoshida Tsutomu , Funaguchi Norihiko , Minato Koichi , Kaito Daizo , Osawa Tomohiro , Yamada Momoko , Hirose Chiemi , Suzuki Akio , Ohno Yasushi
Published: July 2019

Introduction

Adding neurokinin-1 receptor antagonist (NK1RA) to 5-hydroxytryptamine-3 receptor antagonist and dexamethasone (DEX) improved carboplatin (CBDCA)-induced chemotherapy-induced nausea and vomiting (CINV) in patients with thoracic cancer. NK1RAs with high-drug cost are raising medical expenses. Olanzapine (OLZ) is less expensive and can be expected to have an excellent effect on CINV. This phase II trial aimed at evaluating the efficacy and safety of 5 mg OLZ plus granisetron (GRN) and DEX in CBDCA combination therapy with area under curve (AUC) ≥5 mg/mL/min for the prevention of nausea and vomiting in patients with thoracic cancer.

Methods and analysis

This is an open-label, single-arm, multicentre, phase II trial. Patients who receive CBDCA-based therapies (AUC ≥5) and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive a combination of GRN, DEX and OLZ. The primary endpoint is complete response (CR) rate, defined as the absence of emetic episodes and no use of rescue medication for 120 hours after the initiation of CBDCA. Forty-eight patients are required based on our hypothesis that this regimen can improve CR rate from 65% (null hypothesis) to 80% (alternative hypothesis) with a one-sided type I error of 0.1 and a power of 0.8. We set the target sample size at 50 considering dropouts.

Ethics and dissemination

The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.

Trial registration number

UMIN000031267.
Prevalence and risk of pre-eclampsia and gestational hypertension in twin pregnancies: a population-based register study
Authors: Laine Katariina , Murzakanova Gulim , Sole Kristina Baker , Pay Aase Devold , Heradstveit Siri , Räisänen Sari
Published: July 2019

Objectives

The aim of this study was to assess the prevalence and risk of pre-eclampsia and gestational hypertension in twin pregnancies compared with singleton pregnancies.

Design

Population-based cohort study.

Setting

Medical Birth Registry of Norway and Statistics Norway.

Participants

929 963 deliveries with 16 174 twin pregnancies in 1999–2014.

Methods

Pre-eclampsia prevalences in twin and singleton pregnancies were described in percentages. Multivariable regression analyses were performed to assess the risks of pre-eclampsia and gestational hypertension in twin pregnancies compared with those in singleton pregnancies, adjusted for previously known risk factors.

Primary and secondary outcome measures

Prevalence and risk of pre-eclampsia and gestational hypertension.

Results

The prevalence of pre-eclampsia in the study population was 3.7% (3.4% in singleton pregnancies, 11.8% in twin pregnancies (p=0.001)). The OR for pre-eclampsia in twin pregnancies was three to fourfold compared with singleton pregnancies (OR 3.78; 95% CI 3.59 to 3.96). After adjustment for known risk factors, twin pregnancy remained an independent risk factor for pre-eclampsia (adjusted OR 4.07; 95% CI 3.65 to 4.54). The prevalence of gestational hypertension was 1.7% in women with singleton pregnancies and 2.2% in those with twin pregnancies (OR 1.27; 95% CI 1.14 to 1.41). After adjustment for known risk factors, gestational hypertension was not significantly associated with twin pregnancy.

Conclusions

The risk of pre-eclampsia in twin pregnancies was three to fourfold compared with singleton pregnancies, regardless of maternal age, parity, educational level, smoking, maternal comorbidity or in vitro fertilisation. The risk of gestational hypertension was not increased in women with twin pregnancies after adjustment for the main risk factors.
Risk of amyotrophic lateral sclerosis and other motor neuron disease among men with benign prostatic hyperplasia: a population-based cohort study
Authors: Sørensen Trine Toft , Horváth-Puhó Erzsébet , Nørgaard Mette , Ehrenstein Vera , Henderson Victor W
Published: July 2019

Objectives

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder. Sleep disturbance may interfere with clearance of abnormal proteins that aggregate in neurodegenerative diseases. The objective of this study was to examine the association between benign prostatic hyperplasia (BPH), a common disorder causing nocturia and sleep disturbance, and risk of ALS and other motor neuron disease (MND). We hypothesised that men with BPH, in comparison to men in the general population, would be at increased risk.

Design

This is a nationwide, population-based cohort study.

Setting

This study was conducted among the population of Denmark.

Participants

We used linked Danish medical databases to identify all men with a first-time diagnosis of BPH between 1 January 1980 and 30 November 2013 and no prior diagnosis of MND (BPH cohort, n=223 131) and an age-matched general population comparison cohort of men without BPH or MND (n=1 115 642).

Primary outcome measure

The primary outcome is diagnosis of MND after the BPH diagnosis (index) date, with follow-up until MND diagnosis, emigration, death or 30 November 2013.

Results

We used Cox regression to compute adjusted HR, comparing men with and without BPH. After 34 years of follow-up, there were 227 cases of MND in the BPH cohort (incidence rate 0.13/1000 person-years) and 1094 MND cases in the comparison cohort (0.12/1000 person-years; HR 1.05, 95% CI 0.90 to 1.22). Risk did not vary by follow-up time.

Conclusions

BPH is not associated with an increased risk of ALS and other MND. Future studies should examine the relation between other disorders that disrupt sleep and MND risk in men and women.
Food and Agricultural Approaches to Reducing Malnutrition (FAARM): protocol for a cluster-randomised controlled trial to evaluate the impact of a Homestead Food Production programme on undernutrition in rural Bangladesh
Authors: Wendt Amanda S , Sparling Thalia M , Waid Jillian L , Mueller Anna A , Gabrysch Sabine
Published: July 2019

Introduction

Chronic undernutrition affects over 150 million children worldwide and has serious consequences. The causes are complex and include insufficient dietary diversity and poor hygiene practices. Systematic reviews of nutrition-sensitive agricultural interventions concluded that while these hold promise, there is insufficient evidence for their impact on child growth. The Food and Agricultural Approaches to Reducing Malnutrition (FAARM) project is a 1:1 cluster-randomised trial aiming to evaluate the impact of a Homestead Food Production (HFP) programme implemented by Helen Keller International on women’s and children’s undernutrition.

Methods and analysis

The HFP intervention comprises training of women’s groups and asset distribution to support year-round home gardening, poultry rearing and improved nutrition and hygiene practices. Formal trainings are supplemented by behaviour change communication during household visits, and facilitated links between producer groups and market actors. The FAARM trial will examine if and how this complex intervention reduces undernutrition. In 2015, FAARM enrolled married women and their children (0–3 years) in 96 rural settlements of Habiganj district in Sylhet division, Bangladesh. Covariate-constrained randomisation was used to assign 48 settlements to receive a 3-year HFP intervention, with the other 48 acting as controls, targeting over 2700 women. To study impact pathways, a surveillance system collects data on all participants every 2 months. In late 2019, children 0–3 years of age (born during the intervention period) will be surveyed, thus capturing impact during the critical first 1000 days of life. Children’s length/height-for-age z-scores will be compared between intervention and control arms using mixed-effects linear regression. Secondary outcomes include women’s and children’s micronutrient status, dietary intake, dietary diversity and other indicators of child growth, development and morbidity.

Ethics and dissemination

Ethical approval was received in Bangladesh and Germany. Results will be disseminated through peer-reviewed publications and presentations in Bangladesh and internationally.

Trial registration number

NCT02505711; Pre-results.
Undiagnosed microscopic colitis: a hidden cause of chronic diarrhoea and a frequently missed treatment opportunity
Authors: Münch Andreas , Sanders David S , Molloy-Bland Michael , Hungin A Pali S
Published: July 2019

Microscopic colitis (MC) is a treatable cause of chronic, non-bloody, watery diarrhoea, but physicians (particularly in primary care) are less familiar with MC than with other causes of chronic diarrhoea. The colon in patients with MC is usually macroscopically normal. MC can only be diagnosed by histological examination of colonic biopsies (subepithelial collagen band >10 µm (collagenous colitis) or >20 intraepithelial lymphocytes per 100 epithelial cells (lymphocytic colitis), both with lamina propria inflammation). The UK National Health Service exerts downward pressure to minimise colonoscopy referrals. Furthermore, biopsies are often not taken according to guidelines. These factors work against MC diagnosis. In this review, we note the high incidence of MC (comparable to ulcerative colitis and Crohn’s disease) and its symptomatic overlap with irritable bowel syndrome. We also highlight problems with the recommendation by National Health Service/National Institute for Health and Care Excellence guidelines for inflammatory bowel diseases that colonoscopy referrals should be based on a faecal calprotectin level of ≥100 µg/g. Faecal calprotectin is <100 µg/g in over half of individuals with active MC, building into the system a propensity to misdiagnose MC as irritable bowel syndrome. This raises important questions—how many patients with MC have already been misdiagnosed, and how do we address this silent burden? Clarity is needed around pathways for MC management; MC is poorly acknowledged by the UK healthcare system and it is unlikely that best practices are being followed adequately. There is an opportunity to identify and treat patients with MC more effectively.
Simultaneous norovirus outbreak in three Portuguese army bases in the Lisbon region, December 2017
Authors: Lopes-João António , Mesquita J R , de Sousa R , Oleastro M , Penha-Gonçalves C , Nascimento M S J
Published: July 2019

Introduction

Norovirus outbreaks frequently occur in communities and institutional settings acquiring a particular significance in armed forces where prompt reporting is critical. Here we describe the epidemiological, clinical and laboratorial investigation of a multicentre gastroenteritis outbreak that was detected simultaneously in three Portuguese army units with a common food supplier, Lisbon region, between 5 and 6 December 2017.

Methods

Questionnaires were distributed to all soldiers stationed in the three affected army units, and stool specimens were collected from soldiers with acute gastrointestinal illness. Stool specimens were tested for common enteropathogenic bacteria by standard methods and screened for a panel of enteric viruses using a multiplex real-time PCR assay. Food samples were also collected for microbiological analysis. Positive stool specimens for norovirus were further genotyped.

Results

The three simultaneous acute gastroenteritis outbreaks affected a 31 (3.5%) soldiers from a total of 874 stationed at the three units and lasted for 2 days. No secondary cases were reported. Stool specimens (N=11) were negative for all studied enteropathogenic agents but tested positive for norovirus. The recombinant norovirus GII.P16-GII.4 Sydney was identified in all positive samples with 100% identity.

Conclusions

The results are suggestive of a common source of infection plausibly related to the food supplying chain. Although centralisation of food supplying in the army has economic advantages, it may contribute to the multifocal occurrence of outbreaks. A rapid intervention is key in the mitigation of outbreak consequences and in reducing secondary transmission.
Scar burden is an independent and incremental predictor of cardiac resynchronisation therapy response
Authors: Harb Serge C , Toro Saleem , Bullen Jennifer A , Obuchowski Nancy A , Xu Bo , Trulock Kevin M , Varma Niraj , Rickard John , Grimm Richard , Griffin Brian , Flamm Scott D , Kwon Deborah H
Published: July 2019

Objective

Determine the prognostic impact of scar quantification (scar %) by cardiac magnetic resonance (CMR) in predicting heart failure admission, death and left ventricular (LV) function improvement following cardiac resynchronisation therapy (CRT), after controlling for the presence of left bundle branch block (LBBB), QRS duration (QRSd) and LV lead tip location and polarity.

Methods

Consecutive patients who underwent CMR between 2002 and 2014 followed by CRT were included. The primary endpoint was death or heart failure admission. The secondary endpoint was change in ejection fraction (EF) ≥3 months after CRT. Cox proportional hazards, linear regression models and change in the area under the receiver operating characteristic curve (AUC) were used.

Results

A total of 84 patients were included (63% male, 51% with ischaemic cardiomyopathy). After adjusting for clinical factors, presence of LBBB and QRSd and LV lead tip location and polarity, greater scar % remained associated with a higher risk for clinical events (HR=1.06; 95% CI 1.02 to 1.10; p<0.001) and a smaller improvement in EF (slope: −0.61%; 95% CI −0.93% to 0.29%; p<0.001). When adding scar % to QRSd and LBBB, there was significant improvement in predicting clinical events at 3 years (AUC increased to 0.831 from 0.638; p=0.027) and EF increase ≥10% (AUC 0.869 from 0.662; p=0.007).

Conclusion

Scar quantification by CMR has an incremental value in predicting response to CRT, in terms of heart failure admission, death and EF improvement, independent of the presence of LBBB, QRSd, LV lead tip location and polarity.
Managing cluster headache
Authors: Wei Diana Y , Khalil Modar , Goadsby Peter J
Published: July 2019

Cluster headache is a neurological disorder that presents with unilateral severe headache associated with ipsilateral cranial autonomic symptoms. Cluster headache attacks often occur more than once a day, and typically manifesting in bouts. It has a point prevalence of 1 in 1000 and is the most common trigeminal autonomic cephalalgia. This article aims to guide general neurologists to an accurate diagnosis and practical management options for cluster headache patients.
Urbanisation and asthma in low-income and middle-income countries: a systematic review of the urban–rural differences in asthma prevalence
Authors: Rodriguez Alejandro , Brickley Elizabeth , Rodrigues Laura , Normansell Rebecca Alice , Barreto Mauricio , Cooper Philip J
Published: July 2019

Background

Urbanisation has been associated with temporal and geographical differences in asthma prevalence in low-income and middle-income countries (LMICs). However, little is known of the mechanisms by which urbanisation and asthma are associated, perhaps explained by the methodological approaches used to assess the urbanisation-asthma relationship.

Objective

This review evaluated how epidemiological studies have assessed the relationship between asthma and urbanisation in LMICs, and explored urban/rural differences in asthma prevalence.

Methods

Asthma studies comparing urban/rural areas, comparing cities and examining intraurban variation were assessed for eligibility. Included publications were evaluated for methodological quality and pooled OR were calculated to indicate the risk of asthma in urban over rural areas.

Results

Seventy articles were included in our analysis. Sixty-three compared asthma prevalence between urban and rural areas, five compared asthma prevalence between cities and two examined intraurban variation in asthma prevalence. Urban residence was associated with a higher prevalence of asthma, regardless of asthma definition: current-wheeze OR:1.46 (95% CI:1.22 to 1.74), doctor diagnosis OR:1.89 (95% CI:1.47 to 2.41), wheeze-ever OR:1.44 (95% CI:1.15 to 1.81), self-reported asthma OR:1.77 (95% CI:1.33 to 2.35), asthma questionnaire OR:1.52 (95% CI:1.06 to 2.16) and exercise challenge OR:1.96 (95% CI:1.32 to 2.91).

Conclusions

Most evidence for the relationship between urbanisation and asthma in LMICs comes from studies comparing urban and rural areas. These studies tend to show a greater prevalence of asthma in urban compared to rural populations. However, these studies have been unable to identify which specific characteristics of the urbanisation process may be responsible. An approach to understand how different dimensions of urbanisation, using contextual household and individual indicators, is needed for a better understanding of how urbanisation affects asthma.

PROSPERO registration number

CRD42017064470.
Antimicrobial peptides, disease severity and exacerbations in bronchiectasis
Authors: Sibila Oriol , Perea Lídia , Cantó Elisabet , Shoemark Amelia , Cassidy Diane , Smith Alexandria Holly , Suarez-Cuartin Guillermo , Rodrigo-Troyano Ana , Keir Holly R , Oriano Martina , Ong Samantha , Vidal Silvia , Blasi Francesco , Aliberti Stefano , Chalmers James D
Published: July 2019

Rationale

Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease.

Objectives

To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis.

Methods

A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk.

Measurements and main results

AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1(forced expiratory volume in 1 s) andPseudomonas aeruginosainfection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months.

Conclusions

Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated withPseudomonas aeruginosainfection and can predict future risk of exacerbations in bronchiectasis.
Vitamin D for secondary prevention of acute wheeze attacks in preschool and school-age children
Authors: Stefanidis Christos , Martineau Adrian R , Nwokoro Chinedu , Griffiths Christopher J , Bush Andrew
Published: July 2019

Introduction

Vitamin D is best known for its role in bone health; however, the discovery of the vitamin D receptor and the expression of the gene encoding the vitamin D 1α-hydroxylase (CYP27B1) enzyme in a wide variety of tissues including immune cells and respiratory epithelium has led to the discovery of potential roles for vitamin D in the prevention of acute wheeze.

Methods

We review here the literature concerning the relationships between circulating 25-hydroxyvitamin D (25(OH)D) concentration and secondary prevention of acute wheeze attacks in preschool and school-age children.

Results

Epidemiological data suggest that vitamin D insufficiency (25(OH)D <75 nmol/L) is highly prevalent in preschool and school-age children with wheeze. Preschool age children with a history of wheeze attacks and circulating 25(OH)D <75 nmol/L are at increased risk and frequency of future acute wheeze. However, no consistent association between low vitamin D status and risk of acute wheeze is reported in school-age children. Seven randomised controlled trials (RCTs) with relatively small sample sizes (30–430) and variable quality showed inconsistent results regarding the effect of oral vitamin D supplementation during childhood on the risk of asthma attacks, asthma symptom control, inhaled corticosteroid requirements, spirometry and unscheduled healthcare attendances for wheeze. A RCT showed that vitamin D supplementation had no effect on the frequency of unplanned healthcare attendances due to acute wheeze in 22 preschool children.

Discussion

An evidence-based recommendation for the use of vitamin D as a preventive therapy for wheeze attacks cannot be made until results of further trials are available. The assessment of circulating 25(OH)D concentration and the optimisation of vitamin D status to prevent acute respiratory tract infections, and to maintain skeletal and general health in preschool and school-age children with acute wheeze is worthwhile in its own right, but whether this will reduce the risk of acute wheeze attacks is unclear.
Ventilation following established ARDS: a preclinical model framework to improve predictive power
Authors: Oakley Charlotte , Koh Marissa , Baldi Rhianna , Soni Sanooj , O'Dea Kieran , Takata Masao , Wilson Michael
Published: July 2019

Background

Despite advances in understanding the pathophysiology of acute respiratory distress syndrome, effective pharmacological interventions have proven elusive. We believe this is a consequence of existing preclinical models being designed primarily to explore biological pathways, rather than predict treatment effects. Here, we describe a mouse model in which both therapeutic intervention and ventilation were superimposed onto existing injury and explored the impact of β-agonist treatment, which is effective in simple models but not clinically.

Methods

Mice had lung injury induced by intranasal lipopolysaccharide (LPS), which peaked at 48 hours post-LPS based on clinically relevant parameters including hypoxaemia and impaired mechanics. At this peak of injury, mice were treated intratracheally with either terbutaline or tumour necrosis factor (TNF) receptor 1-targeting domain antibody, and ventilated with moderate tidal volume (20 mL/kg) to induce secondary ventilator-induced lung injury (VILI).

Results

Ventilation of LPS-injured mice at 20 mL/kg exacerbated injury compared with low tidal volume (8 mL/kg). While terbutaline attenuated VILI within non-LPS-treated animals, it was ineffective to reduce VILI in pre-injured mice, mimicking its lack of clinical efficacy. In contrast, anti-TNF receptor 1 antibody attenuated secondary VILI within pre-injured lungs, indicating that the model was treatable.

Conclusions

We propose adoption of a practical framework like that described here to reduce the number of ultimately ineffective drugs reaching clinical trials. Novel targets should be evaluated alongside interventions which have been previously tested clinically, using models that recapitulate the (lack of) clinical efficacy. Within such a framework, outperforming a failed pharmacologic should be a prerequisite for drugs entering trials.
Chromoblastomycosis in two giant ditch frogs also known as mountain chicken frogs (Leptodactylus fallax)
Authors: Croci Martina , Klausmann Stefanie , Hatt Jean‐Michel , Schmitt Sarah , Hilbe Monika
Published: July 2019

Because of sudden death of several frogs following the renewal of a terrarium, two giant ditch frogs (Leptodactylus fallax) were submitted for post‐mortem examination. The animals displayed extensive erythematous to ulcerative skin lesions as well as multiple granulomas in the liver, kidney and skeletal musculature. In skin lesions as well as in the brownish granulomas, pigmented fungal sclerotic bodies were found in addition to pigmented hyphal structures, though less common. The fungal pathogen, although not further classified in this study was identified as the etiological agent for chromoblastomycosis (synonym: chromomycosis), a leading cause of fatal systemic disease in poikilothermic animals. It is also a cause of chronic skin disease in human beings and therefore a potential zoonotic agent.
Severe persistent canine oral papillomatosis a multimodal approach including interferon alpha‐2B, CPV‐1 autologous vaccine, CO2 laser ablation and aggressive cryotherapy
Authors: Levinson Matthew , Kirby Allison , Richman Austin , Hall Melissa
Published: July 2019

A 3‐year‐old, 29.5 kg female, spayed, labrador retriever cross with a 5‐month history of severe, persistent papillomas affecting the oral mucous membranes was successfully treated using a multimodal approach that included staged aggressive cryotherapy. On presentation, verrucous growths varying in sizes of 2 mm–3 cm were appreciated affecting all tissues of the oral cavity. There were two alopecic, pedunculated growths with frond‐like projections approximately 4 mm by 4 mm and 1 cm by 4 mm on the left pelvic paw. While the growths on the paws resolved with minimal intervention, the oral verrucous growths remained. A combination of interferon alpha‐2B, canine papillomavirus‐1 autologous vaccine, surgical excision, carbon dioxide laser ablation and aggressive cryotherapy led to complete resolution and continued remission of the canine oral viral papillomas.
MRI findings in two West Highland White Terrier dogs with hepatic encephalopathy secondary to portosystemic shunt
Authors: Fernandes Ricardo , Driver Colin , Rose J H , Rusbridge Clare
Published: July 2019

A portosystemic shunt is an abnormal communication between the portal vascular system and the systemic circulation. A significant number of clinical signs associated with portosystemic shunting result from hepatic encephalopathy (HE); a syndrome encompassing neurological signs such as including changes in behaviour, ataxia, unresponsiveness, pacing, circling, blindness, seizures, coma and death. We present two West Highland White Terrier dogs diagnosed with HE based on clinical signs, bile acid stimulation test and imaging of the abnormal vessel communicating the portal and the systemic circulation. Magnetic resonance sequences of the brain revealed a poorly marginated and diffuse, bilateral and symmetric hyperintense lesions on T2‐weighted, fluid attenuation inversion recovery and diffusion‐weighted sequences relative to the brain parenchyma including the medial longitudinal fasciculus and reticular formation in the brainstem. No abnormalities were detected on T1‐weighted sequences.
Can the outcome of an impaired oral glucose absorption test in horses be improved with fat supplementation and dietary modifications?
Authors: Galinelli NIcolas Cayetano , Wambacq Wendy , Lefère Laurence , Paulussen Ellen , Hesta Myriam
Published: July 2019

Malabsorption syndrome results in impaired nutrient digestion/absorption. Diagnostic tests in horses are focused on reduced carbohydrate absorption demonstrated by abnormal oral glucose tolerance test. However, to determine the definitive diagnosis a biopsy should be performed. The objective was to evaluate the progress of horses believed to be suffering from malabsorption syndrome without other infectious conditions, following institution of appropriate dietary advice. Medical records of 15 horses admitted to the equine hospital of Ghent University (2014–2017) were reviewed. All horses had received corticosteroid treatment and individual dietary advice. All horse owners were contacted in 2017 for a follow‐up. Most horses (86 per cent) had tolerated the recommended diets well and gained weight. Owners noticed the greatest improvements at three and six months after starting the diet. Adequate dietary formulation may therefore be a valuable adjunct to medical treatment. However, it may take several months before increases in bodyweight and condition are seen.
Primary defects in lipid handling and resistance to exercise in myotubes from obese donors with and without type 2 diabetes
Authors: Løvsletten Nils Gunnar , Rustan Arild C. , Laurens Claire , Thoresen G. Hege , Moro Cedric , Nikolić Nataša
Published: July 2019

Several studies have shown that human primary myotubes retain the metabolic characteristic of their donors in vitro. We have demonstrated, along with other researchers, a reduced lipid turnover and fat oxidation rate in myotubes derived from obese donors with and without type 2 diabetes (T2D). Because exercise is known to increase fat oxidative capacity in skeletal muscle, we investigated if in vitro exercise could restore primary defects in lipid handling in myotubes of obese individuals with and without T2D compared with lean nondiabetic donors. Primary myotubes cultures were derived from biopsies of lean, obese, and T2D subjects. One single bout of long-duration exercise was mimicked in vitro by electrical pulse stimulation (EPS) for 24 h. Lipid handling was measured using radiolabeled palmitate, metabolic gene expression by real-time qPCR, and proteins by Western blot. We first showed that myotubes from obese and T2D donors had increased uptake and incomplete oxidation of palmitate. This was associated with reduced mitochondrial respiratory chain complex II, III, and IV protein expression in myotubes from obese and T2D subjects. EPS stimulated palmitate oxidation in lean donors, while myotubes from obese and T2D donors were refractory to this effect. Interestingly, EPS increased total palmitate uptake in myotubes from lean donors while myotubes from T2D donors had a reduced rate of palmitate uptake into complex lipids and triacylglycerols.

Novelty Myotubes from obese and T2D donors are characterized by primary defects in palmitic acid handling. Both obese and T2D myotubes are partially refractory to the beneficial effect of exercise on lipid handling.
circ-NOTCH1 acts as a sponge of miR-637 and affects the expression of its target gene Apelin to regulate gastric cancer cell growth
Authors: Guan Encui , Xu Xiaoguang , Xue Fangxi
Published: July 2019

Gastric cancer (GC) is a major cause of cancer-related deaths worldwide, and has a low survival rate, low cure rate, high recurrence rate, and poor prognosis. Recent studies have indicated that circular RNAs (circRNAs) have important functions in the occurrence and progression of GC. Studies on circ-NOTCH1, which was shown to be highly expressed in GC, have indicated that miR-637 binds to circ-NOTCH1 at multiple sites, and a dual-luciferase reporter gene assay further confirmed that miR-637 indeed targeted circ-NOTCH1 and Apelin. Circ-NOTCH1 and Apelin are highly expressed in GC cells and tissues, whereas the expression of miR-637 is reduced. Circ-NOTCH1 and miR-637 do not regulate each other’s expression levels, but circ-NOTCH1significantly upregulates the expression of the miR-637 target gene Apelin, whereas miR-637 inhibites the expression of Apelin. Examination of GC cells showed that circ-NOTCH1 enhances cell proliferation and invasiveness, and reduces cell apoptosis; these effects were reversed by miR-637, which could terminate the above effects of circ-NOTCH1. When co-transfected with the circ-NOTCH1 overexpression plasmid and Apelin siRNAs, there were no obvious changes to the levels of cell proliferation, apoptosis, or invasiveness. Therefore, in GC cells, circ-NOTCH1 inhibits the transcriptional activity of miR-637, thereby upregulating the expression of its target gene Apelin and regulating cell proliferation, apoptosis, and invasiveness. This finding provides more experimental evidence for the function of circRNA in GC.
Atypical chromatin structure of immune-related genes expressed in chicken erythrocytes
Authors: Jahan Sanzida , Beacon Tasnim H. , Xu Wayne , Davie James R.
Published: July 2019

The major biological role of red blood cells is to carry oxygen to the tissues in the body. However, another role of the erythroid cell is to participate in the immune response. Mature erythrocytes from chickens express Toll-like receptors and several cytokines in response to stimulation of the immune system. We previously reported the application of a biochemical fractionation protocol to isolate highly enriched transcribed DNA from polychromatic erythrocytes from chickens. In conjunction with next-generation DNA, RNA sequencing, chromatin immunoprecipitation-DNA sequencing, and formaldehyde-assisted isolation of regulatory elements (FAIRE) sequencing, we identified the active chromosomal compartments and determined their structural signatures in relation to expression levels. Here, we present the detailed chromatin characteristics of erythroid genes participating in the innate immune response. Our studies revealed an atypical chromatin structure for several genes coding for Toll-like receptors, interleukins, and interferon regulatory factors. The body of these genes had nucleosome-free regions intermingled with nucleosomes modified with H3K4me3 and H3K27ac, suggesting a dynamic unstable chromatin structure. We further show that human genes involved in cell identity have gene bodies with the same chromatin-instability features as the chicken polychromatic erythrocyte genes participating in the innate immune response.
Observations: What for?
Authors: Şengör A.M. Celâl
Published: July 2019

Observations are to test hypotheses and without hypotheses there can be no usable observations. Geology students should be taught to be independent, bold, imaginative thinkers before they become assiduous observers.
Next-generation sequencing reveals endosymbiont variability in cassava whitefly,Bemisia tabaci, across the agro-ecological zones of Kerala, India
Authors: Harish E.R. , ManiChellappan  , MakeshKumar T. , Mathew Deepu , Ranjith M.T. , Girija D.
Published: July 2019

Silverleaf whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is one of the most notorious invasive insect pests, infesting more than 900 species of plants and spreading more than 200 viral diseases. This polyphagous agricultural pest harbours diverse bacterial communities in its gut, which perform multiple functions in whiteflies, including nutrient provisioning, amino acid biosynthesis, and virus transmission. The present exploratory study compares the bacterial communities associated with silverleaf whitefly infesting cassava, also known as cassava whitefly, collected from two different zones (zone P: plains; zone H: high ranges), from Kerala, India, using next-generation sequencing of 16S rDNA. The data sets for these two regions consisted of 1 321 906 and 690 661 high-quality paired-end sequences with mean length of 150 bp. Highly diverse bacterial communities were present in the sample, containing approximately 3513 operational taxonomic units (OTUs). Sequence analysis showed a marked difference in the relative abundance of bacteria in the populations. A total of 16 bacterial phyla, 27 classes, 56 orders, 91 families, 236 genera, and 409 species were identified from the P population, against 16, 31, 60, 88, 225, and 355, respectively, in the H population. Arsenophonus sp. (Enterobacteriaceae), which is important for virus transmission by whiteflies, was relatively abundant in the P population, whereas in the H population Bacillus sp. was the most dominant group. The association of whitefly biotypes and secondary symbionts suggests a possible contribution of these bacteria to host characteristics such as virus transmission, host range, insecticide resistance, and speciation.
FRACTAL MATHEMATICAL MODEL FOR INVESTIGATING THE MICRO-DISPLACEMENT BEHAVIOR OF A TEMPERATURE-DEPENDENT NON-NEWTONIAN FRACTURING LIQUID FLOW IN TIGHT MATRIX
Authors: MENG XINGBANG , WANG XIUKUN , CHEN JIANGUO , GENG DANDAN
Published: July 2019

Micro-displacement behavior during hydraulic fracturing greatly influences damage formation. Formation temperature and the non-Newtonian behavior of fracturing liquid are the major influencing factors in the micro-displacement process. In this work, to investigate the influencing factors on micro-displacement process, we built a mathematical model for the micro-displacement of a fracturing liquid on the basis of the fractal theory. Then, the analytical expression for penetration equation was obtained according to the model, and explicit solution for the relationship between the volume driven into formation and time was derived. Finally, the influences of non-Newtonian behavior, formation temperature, wettability, and pore size complexity on the micro-displacement process were discussed. Results show that the decrease in formation temperature or decrease in the non-Newtonian degree of fracturing liquid reduce fracturing liquid leakage.
QUASISYMMETRIC PACKING-MINIMALITY OF MORAN SETS
Authors: LI YANZHE , QIAO YU , LOU MANLI
Published: July 2019

In this paper, we prove that a large class of Moran sets on the line with packing dimension 1 is quasisymmetrically packing-minimal.
CONSTRUCTION OF NONLINEAR HIDDEN VARIABLE FRACTAL INTERPOLATION FUNCTIONS AND THEIR STABILITY
Authors: KIM JINMYONG , KIM HYONJIN , MUN HAKMYONG
Published: July 2019

This paper presents a method to construct nonlinear hidden variable fractal interpolation functions (FIFs) and their stability results. We ensure that the projections of attractors of vector-valued nonlinear iterated function systems (IFSs) constructed by Rakotch contractions and function vertical scaling factors are graphs of some continuous functions interpolating the given data. We also give an explicit example illustrating obtained results. Then, we get the stability results of the constructed FIFs in the case of the generalized interpolation data having small perturbations.
REFLECTED BROWNIAN MOTION ON SIMPLE NESTED FRACTALS
Authors: KALETA KAMIL , OLSZEWSKI MARIUSZ , PIETRUSKA-PAŁUBA KATARZYNA
Published: July 2019

For a large class of planar simple nested fractals, we prove the existence of the reflected diffusion on a complex of an arbitrary size. Such a process is obtained as a folding projection of the free Brownian motion from the unbounded fractal. We give sharp necessary geometric conditions for the fractal under which this projection can be well defined, and illustrate them by numerous examples. We then construct a proper version of the transition probability densities for the reflected process and we prove that it is a continuous, bounded and symmetric function which satisfies the Chapman–Kolmogorov equations. These provide us with further regularity properties of the reflected process such us Markov, Feller and strong Feller property.