bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal growth and fetoplacental circulation in pregnancies following bariatric surgery: a prospective study
Authors: Maric T , Kanu C , Muller DC , Tzoulaki I , Johnson MR , Savvidou MD
Published: January 2020

Objective

To investigate the intrauterine fetal growth pattern and fetoplacental circulation in pregnancies following bariatric surgery.

Design

Prospective study.

Setting

Maternity Unit, UK.

Population

One hundred and sixty‐two pregnant women; 54 with previous bariatric surgery and 108 with no surgery but similar booking body mass index.

Methods

Participants were seen at 11–14, 20–24, 30–33 and 35–37 weeks of gestation and an oral glucose tolerance test (OGTT) was performed at 27–30 weeks. Fetal head and abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW) and fetoplacental Dopplers were measured at three time‐points in pregnancy. Birthweight (BW) was recorded. Variables were modelled after adjustment for maternal/pregnancy characteristics. Model estimates are reported as posterior means and quantile‐based 90% credible intervals (CrI).

Main outcome measures

Fetal biometry, fetoplacental Doppler, BW.

Results

Compared with the no surgery group, the post‐bariatric surgery group had lower EFW during gestation (up to −120 g; [−189 g, −51 g] lighter) at 35–37 weeks, with smaller AC and FL. Similarly, infants of mothers with previous bariatric surgery had lower average BW [−202 g [−330 g, −72 g] lighter). Overall, there was no difference in the fetoplacental Doppler indices between groups but maternal glucose levels at OGTT were positively correlated with third‐trimester EFW and BW.

Conclusions

Fetuses of women with previous bariatric surgery are smaller during pregnancy and at birth, compared with those of women without such surgery, and this may be related to the lower maternal glucose levels seen in the former population. The fetoplacental circulation appears not to be altered by maternal weight loss surgery.

Tweetable abstract

Offspring of post‐bariatric women are smaller during pregnancy and at birth but this is not due to placental insufficiency.
Living‐donor liver transplantation for children with tyrosinemia type I
Authors: Liu Yuan , Luo Yi , Xia Lei , Qiu Bi Jun , Zhou Tao , Feng Ming Xuan , Xue Feng , Chen Xiao Song , Han Lian Shu , Zhang Jian Jun , Xia Qiang
Published: January 2020

Objective

To evaluate the efficacy of living‐donor liver transplantation (LDLT) in children with tyrosinemia type I.

Methods

Altogether 10 patients diagnosed with tyrosinemia type I underwent LDLT between June 2013 and April 2019. Cirrhosis was the indication for LDLT in all 10 patients, and hepatocellular carcinoma (HCC) was suspected in nine. Patients' outcomes, including liver function, restoration of metabolism, quality of life and physical development, were analyzed after LDLT.

Results

All recipients were alive with a normal liver function after a median follow‐up period of 49 months. Pathological examinations detected HCC in one patient, dysplasia in five and cirrhosis in all. Nine patients were found to have elevated alpha‐fetoprotein level, and their median alpha‐fetoprotein level dropped from 2520 ng/mL to a normal level after LDLT, with no recurrence of HCC detected during the follow‐up. Tyrosine metabolism was restored to its normal level with normalized plasma tyrosine and succinylacetone concentrations. Moreover, urinary succinylacetone excretion decreased significantly during the follow up. LDLT improved patients’ renal tubular function, as evidenced by the normalized plasma phosphate concentration and improved glomerular filtration rate. Severe rickets symptoms, including spontaneous fractures and bone pain, were also ameliorated. Improved motor function was reported by all patients' parents during the follow‐up. Dietary restriction was no longer required, which was associated with a favorable catch‐up in growth and improved quality of life. Complete resolution of hypertrophic cardiomyopathy was observed one year after LDLT in one patient.

Conclusion

LDLT is an effective treatment for patients with end‐stage liver disease resulting from tyrosinemia type I.
LncRNA SNHG16 promotes non‐small cell lung cancer development through regulating EphA2 expression by sponging miR‐520a‐3p
Authors: Yu Lin , Chen Dewen , Song Jie
Published: January 2020

Background

Recent evidence has found that lncRNA small nucleolar RNA host gene 16 (SNHG16) was associated with cell carcinogenesis in NSCLC. Here, we further investigated the precise functions and mechanisms of SNHG16 in NSCLC progression.

Methods

The expression of SNHG16, microRNA (miR)‐520a‐3p and EPH Receptor A2 (EphA2) was measured using quantitative real‐time polymerase chain reaction and western blot, respectively. Cell proliferation was determined using 3‐(4, 5)‐dimethylthiahiazo (−z‐y1)‐3, 5‐di‐phenytetrazoliumromide (MTT) assay. The migrated and invaded cells were measured by Transwell assay. Flow cytometry was used to detect apoptotic cells. The interaction between miR‐520a‐3p and SNHG16 or EphA2 was confirmed using a dual‐luciferase reporter assay.

Results

We found that SNHG16 was upregulated in NSCLC tissues and cell lines, knockdown of SNHG16 inhibited cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. MiR‐520a‐3p directly bound to SNHG16 and miR‐520a‐3p, and SNHG16 acted as a ceRNA in regulating EphA2 through competitively binding to miR‐520a‐3p. Additionally, rescue assay exhibited the anticancer activity mediated by SNHG16 knockdown on NSCLC could be reversed by miR‐520a‐3p inhibition or EphA2 overexpression.

Conclusion

SNHG16 promoted NSCLC development by regulating the miR‐520a‐3p/EphA2 axis, suggesting novel insights for the pathogenesis of NSCLC and new potential therapeutic targets for the treatment of NSCLC.

Key points

Knockdown of SNHG16 inhibited NSCLC cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo.

SNHG16 directly interacted with miR‐520a‐3p.

EphA2 was a target of miR‐520a‐3p.

SNHG16 could regulate the expression of EphA2 by binding to miR‐520a‐3p.

SNHG16 promoted NSCLC development by regulating the miR‐520a‐3p/EphA2 axis.
Presence–absence sampling for estimating plant density using survey data with variable plot size
Authors: Ståhl Göran , Ekström Magnus , Dahlgren Jonas , Esseen Per‐Anders , Grafström Anton , Jonsson Bengt‐Gunnar
Published: January 2020

Presence–absence sampling is an important method for monitoring state and change of both individual plant species and communities. With this method, only the presence or absence of the target species is recorded on plots and thus the method is straightforward to apply and less prone to surveyor judgement compared to other vegetation monitoring methods. However, in the basic setting, all plots must be equally large or otherwise it is unclear how data should be analysed. In this study, we propose and evaluate five different methods for estimating plant density based on presence–absence registrations from surveys with variable plot sizes.

Using artificial plant population data as well as empirical data from the Swedish National Forest Inventory, we evaluated the performance of the proposed methods. The main analysis was conducted through sampling simulation in artificial populations, whereby bias and variance of density estimators for the different methods were quantified and compared.

Both for state and change estimation of plant density, we found that the best method to handle variable plot size was to perform generalized least squares regression, using plot size as an independent variable. Methods where plots smaller than a certain threshold were excluded or their registrations recalculated were, however, almost as good. Using all registrations as if they were obtained from plots with the nominal plot size resulted in substantial bias.

Our findings are important for plant population studies in a wide range of environmental monitoring programmes. In these programmes, plots are typically randomly laid out and may be located across boundaries between different land‐use or land‐cover classes, resulting in subplots of variable size. Such splitting of plots is common when large plots are used, for example, with the 100 m2plots used in the Swedish National Forest Inventory. Our methods overcome problems to estimate plant density from presence–absence data observed in plots that vary in size.
A common signaling pathway leading to degranulation in mast cells and its regulation by CCR1‐ligand
Authors: Chang Hyeun Wook , Kanegasaki Shiro , Jin Fansi , Deng Yifeng , You Zhiwei , Chang Jae‐Hoon , Kim Dong Young , Timilshina Maheshwor , Kim Jae‐Ryong , Lee Youn Ju , Toyama‐Sorimachi Noriko , Tsuchiya Tomoko
Published: January 2020

Background

Signal transduction pathways mediated by various receptors expressed on mast cells are thought to be complex, and inhibitory signals that turn off activating signals are not known.

Methods

Upstream signaling cascades mediated by several known receptors in bone marrow‐derived mast cells that lead to degranulation and mediator release were studied by immunoblotting and immunoprecipitation. Small interfering RNAs and knockout mice were used to confirm findings.

Results

All ligands tested including IgE/Ag, SCF, HSP70, CCL3, and its valiant eMIP induced phosphorylation of linker for activation of T cells (LAT), which triggered their receptor‐mediated downstream signaling cascades that controlled degranulation and mediator release. Phosphorylation of lymphocyte‐specific protein kinase (Lck) was induced by each ligand, which commonly played an indispensable role in LAT phosphorylation. In contrast, phosphorylation of spleen tyrosine kinase was additionally induced in cells stimulated only with IgE/Ag and SCF, which is also associated with LAT phosphorylation in part. Degranulation and mediator release induced by IgE/Ag, SCF, or HSP70 were enhanced by nanomolar doses of CCR1 ligands CCL3 and eMIP via enhanced LAT phosphorylation. On the other hand, micromolar doses of CCR1 ligand inhibited degranulation and mediator release from mast cells stimulated with IgE/Ag, SCF, or HSP70 by de‐phosphorylation of phosphorylated Lck with Src homology region 2 domain‐containing phosphatase‐1.

Conclusions

Linker for activation of T cells plays a central role in signal transduction pathways in mast cells stimulated with any ligand tested. Dose‐dependent alternate costimulation and inhibition of CCR1 ligands in IgE/Ag‐, SCF‐, or HSP70‐stimulated mast cells occur at the level of Lck‐LAT phosphorylation.
External validation and clinical utility of prognostic prediction models for gestational diabetes mellitus: A prospective cohort study
Authors: Meertens Linda J. E. , Scheepers Hubertina C. J. , van Kuijk Sander M. J. , Roeleveld Nel , Aardenburg Robert , van Dooren Ivo M. A. , Langenveld Josje , Zwaan Iris M. , Spaanderman Marc E. A. , van Gelder Marleen M. H. J. , Smits Luc J. M.
Published: January 2020

Introduction

We performed an independent validation study of all published first trimester prediction models, containing non‐invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated.

Material and methods

Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies.

Results

The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models.

Conclusions

The best performing prediction models showed acceptable performance measures and may enable more personalized medicine‐based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies.
Randomised oral stimulation and exclusive breastfeeding duration in healthy premature infants
Authors: Skaaning Diana , Carlsen Emma , Brødsgaard Anne , Kyhnæb Anne , Pedersen Maj , Ravn Stine , Pryds Ole , Kronborg Hanne
Published: January 2020

Aim

Although exclusive breastfeeding is recommended for all newborn in the first 6 months of life, only 13% of Danish premature infants complies with this. This trial aimed to examine whether oral stimulation prolonged exclusive breastfeeding in premature infants.

Method

A randomised controlled trial was conducted at the Neonatal Intensive Care Unit, Hvidovre Hospital, Denmark between 2016 and 2018. Systematic oral stimulation was performed by the parents after training by occupational therapists. Primary outcome was exclusive breastfeeding duration with 6 months' follow‐up, analysed by intention‐to‐treat.

Results

Included were 211 infants (53% boys) with a mean gestational age of 231 days, allocated in ratio 1:1 to oral stimulation or standard care. There was no difference in exclusive breastfeeding duration between infants orally stimulated and control infants. Thus, for orally stimulated infants, median duration was 122 days (interquartile range 40‐183) in contrast to 154 days (interquartile range 61‐183) for the controls, P value .16. At 6 months of age, 27% of orally stimulated infants were exclusively breastfed compared with 25% of controls.

Conclusion

In healthy premature infants, oral stimulation performed by parents has no long‐lasting effect on breastfeeding duration. Attention should be directed to parental education and involvement.
Aberrant sinus node firing during β‐adrenergic stimulation leads to cardiac arrhythmias in diabetic mice
Authors: Lubberding Anniek F. , Pereira Laetitia , Xue Jianbin , Gottlieb Lisa A. , Matchkov Vladimir V. , Gomez Ana M. , Thomsen Morten B.
Published: January 2020

Aim

Cardiovascular complications, including cardiac arrhythmias, result in high morbidity and mortality in patients with type‐2 diabetes mellitus (T2DM). Clinical and experimental data suggest electrophysiological impairment of the natural pacemaker of the diabetic heart. The present study examined sinoatrial node (SAN) arrhythmias in a mouse model of T2DM and physiologically probed their underlying cause.

Methods

Electrocardiograms were obtained from conscious diabetic db/db and lean control db/+ mice. In vivo SAN function was probed through pharmacological autonomic modulation with isoprenaline, atropine and carbachol. Blood pressure stability and heart rate variability (HRV) were evaluated. Intrinsic SAN function was evaluated through ex vivo imaging of spontaneous Ca2+ transients in isolated SAN preparations.

Results

While lean control mice showed constant RR intervals during isoprenaline challenge, the diabetic mice experienced SAN arrhythmias with large RR fluctuations in a dose‐dependent manner. These arrhythmias were completely abolished by atropine pre‐treatment, while carbachol pretreatment significantly increased SAN arrhythmia frequency in the diabetic mice. Blood pressure and HRV were comparable in db/db and db/+ mice, suggesting that neither augmented baroreceptor feedback nor autonomic neuropathy is a likely arrhythmia mechanism. Cycle length response to isoprenaline was comparable in isolated SAN preparations from db/db and db/+ mice; however, Ca2+ spark frequency was significantly increased in db/db mice compared to db/+ at baseline and after isoprenaline.

Conclusion

Our results demonstrate a dysfunction of cardiac pacemaking in an animal model of T2DM upon challenge with a β‐adrenergic agonist. Ex vivo, higher Ca2+ spark frequency is present in diabetic mice, which may be directly linked to in vivo arrhythmias.
Solidarity tested: The case of the Norwegian Confederation of Trade Unions (LO‐Norway) and its contradictory climate change policies
Authors: Houeland Camilla , Jordhus‐Lier David C. , Angell Frida Hambro
Published: January 2020

The paper examines how organised labour as an important strategic actor in the political economy engages with climate change mitigation policies. By using The Norwegian Confederation of Trade Unions (LO‐Norway) as a case study, we investigate how sectoral unions view the national confederation as a contested space of engagement in which they promote their positions on petroleum extraction and environmental conservation around the Lofoten archipelago. Affiliate unions of LO‐Norway legitimise their policy positions through claims of sectoral and regional representation. The analysis traces the confrontation of these policy positions as inter‐union solidarity was put to the test in the build‐up to the 2017 LO‐Norway congress. While an emerging climate agenda seemingly opened a discursive window for a policy shift within LO‐Norway at the 2017 congress, we show how institutional norms harnessed claims of sectoral and regional dependence and maintained unity within the national confederation.
Lung mechanical properties distinguish children with asthma with normal and diminished lung function
Authors: Comberiati Pasquale , Spahn Joseph D. , Paull Keith , Faino Anna , Cherniack Reuben , Covar Ronina A.
Published: January 2020

Background

Children with asthma, even those with severe persistent disease, can have forced expiratory volume in 1 second (FEV1) values ≥100% of predicted, while others have diminished FEV1.

Objective

We sought to characterize the lung mechanical properties underlying these two asthma phenotypes and the mechanisms explaining the paradox of severe asthmatic children, whom when clinically stable can have an FEV1 >100% of predicted, but during an acute bronchospastic episode can experience a life‐threatening asthma event.

Methods

Lung mechanics were evaluated in three groups of children: asthmatics with FEV1 ≥100% (HFEV1; n = 13), asthmatics with FEV1 ≤80% (LFEV1; n = 14) and non‐asthmatic controls (n = 10). A linear mixed model was used to examine the relationship between volume and static transpulmonary pressures obtained at total lung capacity (TLC); actual TLC %of predicted and flow; and static transpulmonary pressure and flow.

Results

HFEV1 asthmatics had larger airways (FEV1 z‐scores 1.12 vs −2.37; P < .05), greater lung volumes (mean % of predicted TLC 134.8% vs 109.6%; P < .05) and lower airway resistance (mean %of predicted Raw 101.9% vs 199.9%; P < .05) compared to the LFEV1 group. Moreover, HFEV1 asthmatics had significantly reduced elastic recoil pressure (pressure‐volume curve shifted upward and to the left) and higher lung compliance (0.21 vs 00.9 L/cm H2O; P < .05) compared to the LFEV1 group. The pressure‐flow curves revealed the LFEV1 group to have significantly increased resistance to flow in the upstream segment of the airways at all lung volumes studied compared to HFEV1.

Conclusion and Clinical Relevance

HFEV1 asthmatic children display distinct lung mechanical proprieties compared to their LFEV1 asthmatic peers. With loss of elastic recoil pressure, the HFEV1 group could generate normal FEV1 due to proportionally enlarged airways and reduced airway resistance, while airflow limitation in the LFEV1 is due to increased airway resistance. Loss of elastic recoil and interdependence during acute bronchoconstriction episodes may predispose the HFEV1 group to catastrophic reductions in airflow.
Correlation between glucose metabolism and serum steroid hormones in patients with polycystic ovary syndrome
Authors: Li Xuelin , Zhang Tianyue , Li Shengxian , Deng Yuying , Wang Lihua , Tao Tao , Wang Shujie , Gu Yanyun , Gu Weiqiong , Hong Jie , Liu Wei , Wang Weiqing , Zhang Yifei
Published: January 2020

Objective

Polycystic ovary syndrome (PCOS) is associated with an increased prevalence of dysglycaemia, which includes impaired glucose tolerance and type 2 diabetes mellitus (T2DM). Patients with PCOS demonstrate abnormal patterns of steroid hormones. Here, we analyse the correlation between glucose metabolism and serum steroid hormones in PCOS.

Design

Observational double‐centre study.

Patients

914 patients with PCOS.

Measurements

We assessed the glucose metabolism status of all patients according to the 1999 WHO criteria. Serum steroid hormones were measured by liquid chromatography‐tandem mass spectrometry.

Results

The median age of the patients was 26 years (interquartile range: 21‐30), and 40.6% (371/914) had abnormal glucose metabolism: 29.3% (268/914) had prediabetes, and 11.3% (103/914) had T2DM. Correlation analysis not adjusting for confounding factors revealed that serum aldosterone, androstenedione, oestrone, pregnenolone and the free androgen index were positively correlated, while progesterone was negatively correlated with the risk of abnormal glucose metabolism. After adjusting for age, body mass index and fasting insulin levels in the logistic regression model, only aldosterone (P = .013), androstenedione (P = .046) and oestrone (P = .014; in quartiles) were correlated with the risk of abnormal glucose metabolism.

Conclusions

This study indicates a high prevalence of prediabetes and T2DM in patients with PCOS. Furthermore, there were positive correlations of serum aldosterone, androstenedione and oestrone with the risk of abnormal glucose metabolism after adjusting for confounding factors.
Evolutionary relationships of the ancient fern lineage the adder's tongues (Ophioglossaceae) with description of Sahashia gen. nov
Authors: Zhang Liang , Fan Xue‐Ping , Petchsri Sahanat , Zhou Lin , Pollawatn Rossarin , Zhang Xin , Zhou Xin‐Mao , Thi Lu Ngan , Knapp Ralf , Chantanaorrapint Sahut , Limpanasittichai Ponpipat , Sun Hang , Gao Xin‐Fen , Zhang Li‐Bing
Published: January 2020

As an ancient lineage of ferns, Ophioglossaceae are evolutionarily among the most fascinating because they have the highest chromosome count of any known organism as well as the presence of sporophores, subterranean gametophytes, eusporangiate sporangia without annuli, and endophytic fungi. Previous studies have produced conflicting results, identifyingsome lineages with unresolved relationships, and have paid much attention to the subfamily Botrychioideae. But the other species‐rich subfamily, Ophioglossoideae, has remained largely understudied and only up to 12 accessions of Ophioglossoideae have been sampled. In this study, DNA sequences of seven plastid markers of 149 accessions (75 in Ophioglossoideae) representing approximately 82 species (approximately 74% of estimated species diversity sensu J. Syst. Evol., 2016, 54, 563) in the family, and two Marattiaceae and two Psilotaceae, are used to infer a phylogeny. Our major results include: (1) Ophioglossaceae are resolved as monophyletic with strong support, and so are all four subfamilies and genera sensu PPG I except Botrypus and Ophioglossum; (2) a new genus Sahashia is segregated from Botrypus so that the monophyly of Botrypus can be retained; (3) the monophyly of Ophioglossum in its current circumscription is uncertain in spite of our large character sampling; (4) there is substantial cryptic speciation in Ophioderma detected by our molecular and morphological study; (5) the recognition of Holubiella is advocated based on its morphology and its sister relationship with Sceptridium; and (6) a novel sister relationship between Botrychium and the JHS clade (Japanobotrychium + (Holubiella + Sceptridium)) is discovered.
Titanium implant surface properties enhance osseointegration in ovariectomy induced osteoporotic rats without pharmacologic intervention
Authors: Lotz Ethan M. , Cohen David J. , Schwartz Zvi , Boyan Barbara D.
Published: January 2020

Objectives

This study determined whether implant surfaces that promote osseointegration in normal rats can promote osseointegration in osteoporotic rats without pharmacologic intervention.

Materials and Methods

Virgin female 8‐month‐old CD Sprague Dawley rats (N = 25) were ovariectomized. At 6 weeks, microstructured/non‐nanostructured/hydrophobic, microstructured/nanostructured/hydrophobic, or microstructured/nanostructured/hydrophilic Ti implants (Ø2.5 × 3.5 mm; Institut Straumann AG, Basel, Switzerland) were placed in the distal metaphysis of each femur. At 28 days, bone quality and implant osseointegration were assessed using microCT, histomorphometrics, and removal torque values (RTVs). Calvarial osteoblasts were isolated and cultured for 7 days on Ø15 mm Ti disks processed to exhibit similar surface characteristics as the implants used for the in vivo studies. The phenotype was assessed by measuring the production of osteocalcin, osteoprotegerin, osteopontin, BMP2, VEGF, and RANKL.

Results

Microstructured/nanostructured/hydrophilic implants promoted increased bone‐to‐implant contact and RTVs in vivo and increased osteoblastic marker production in vitro compared to microstructured/non‐nanostructured/hydrophobic and microstructured/nanostructured/hydrophobic implants, suggesting that osseointegration occurs in osteoporotic animals, and implant surface properties improve its rate.

Conclusions

Although all modified implants were able to osseointegrate in rats with OVX‐induced osteoporosis without pharmacologic intervention, the degree of osseointegration was greater around microstructured/nanostructured/hydrophilic implant surfaces. These results suggest that when appropriate microstructure is present, hydrophilicity has a greater influence on Ti implant osseointegration compared to nanostructures. Moreover, modified implant surfaces can exert their control over the altered bone turnover observed in osteoporotic patients to stimulate functional osseointegration. These results provide critical insight for developing implants with improved osseointegration in patients with metabolic disorders of bone remodeling.
Ethical considerations when conservation research involves people
Authors: Brittain Stephanie , Ibbett Harriet , de Lange Emiel , Dorward Leejiah , Hoyte Simon , Marino Agnese , Milner‐Gulland E. J. , Newth Julia , Rakotonarivo Sarobidy , Veríssimo Diogo , Lewis Jerome
Published: January 2020

Social science is becoming increasingly important in conservation, with more studies involving methodologies that collect data from and about people. Conservation science is a normative and applied discipline designed to support and inform management and practice. Poor research practice risks harming participants and, researchers, and can leave negative legacies. Often, those at the forefront of field‐based research are early‐career researchers, many of whom enter their first research experience ill‐prepared for the ethical conundrums they may face. We draw on our own experiences as early‐career researchers to illuminate how ethical challenges arise during conservation research that involves human participants. Specifically, we considered ethical review procedures, conflicts of values, and power relations, and devised broad recommendations on how to navigate ethical challenges when they arise during research. In particular, we recommend researchers apply reflexivity (i.e., thinking that allows researchers to recognize the effect researchers have on the research) to help navigate ethical challenges and encourage greater engagement with ethical review processes and the development of ethical guidelines for conservation research that involves human participants. Such guidelines must be accompanied by the integration of rigorous ethical training into conservation education. We believe our experiences are not uncommon and can be avoided and hope to spark discussion to contribute to a more socially just conservation.
Associations between gastric histopathology and the occurrence of colonic polyps
Authors: Sonnenberg A. , Turner K. O. , Genta R. M.
Published: January 2020

Aim

Compromise of the gastric acid barrier may facilitate bacterial invasion of the lower intestinal tract and promote the development of colonic neoplasia. Our study aimed to test the associations between histopathological abnormalities of the upper and lower gastrointestinal tract in patients undergoing bidirectional endoscopy.

Method

The Inform Diagnostics database is a national electronic repository of histopathological records of patients distributed throughout the USA. A case–control study of 302 061 patients, 163 168 of whom had colonic polyps, evaluated whether the occurrence of colonic polyps was influenced by the presence of the following gastro‐oesophageal diagnoses: gastric Helicobacter pylori infection, gastric intestinal metaplasia, fundic gland polyps and gastric hyperplastic polyps. The influence of individual diagnoses on the occurrence of colonic polyps was expressed as odds ratios with their 95% confidence intervals.

Results

The odds ratio for tubular adenomas being associated with gastric H. pylori was 1.53 (1.49–1.58), with intestinal metaplasia 1.65 (1.59–1.71), with fundic gland polyps 1.49 (1.45–1.54) and with gastric hyperplastic polyps 1.85 (1.75–1.96). The odds ratio for sessile serrated polyps being associated with gastric H. pylori was 1.03 (0.96–1.10), with intestinal metaplasia 1.21 (1.13–1.30), with fundic gland polyps 1.79 (1.69–1.89) and with gastric hyperplastic polyps 1.52 (1.35–1.71.

Conclusion

A diminished gastric acid barrier function, which occurs in various upper gastrointestinal diseases associated with lowered gastric acid output, may promote the development of colonic neoplasia.
Barriers to Social Inclusion with the Egyptian Museums; New Approach Towards Disability
Authors: Zakaria Nevine Nizar
Published: January 2020

Each person in Egypt, including the 15 million with disabilities and more than 3.5 million who are 65 and older, – have the right to access museums without barriers. Egyption law, requires accommodations for each disabled person so they have equal opportunity to participate in the cultural life of the community. Unfortunately, Egypt's museums have not prioritized accessibility, despite the legislation that establishes these rights of access. This forum identifies the source of the problem as a problem of public discourse and political will rather than the legal principles that have laid the foundations for universal design in western cultures. The author proposes a new strategic vision for Egypt's museums to work within their enabling legislation to interpret state policy in ways that can accelerate inclusive practices. This strategy acknowledges that the Egyptian context where accommodation has focused on a medical model, and acknowledges that the cultural challenges with implementation of a social model requires a shift in thinking that is already been achieved in other nations. Moreover, by working within their governing systems, the author suggests that the museum can lead a shift in public discourse toward removing environmental barriers in ways that benefit all people in Egypt rather than the medical model that promotes prejudice and victimhood of those who require accommodation.
“I don't know but I know who to ask”: 12‐month‐olds actively seek information from knowledgeable adults
Authors: Bazhydai Marina , Westermann Gert , Parise Eugenio
Published: January 2020

Active social communication is an effective way for infants to learn about the world. Do pre‐verbal and pre‐pointing infants seek epistemic information from their social partners when motivated to obtain information they cannot discover independently? The present study investigated whether 12‐month‐olds (N = 30) selectively seek information from knowledgeable adults in situations of referential uncertainty. In a live experiment, infants were introduced to two unfamiliar adults, an Informant (reliably labeling objects) and a Non‐Informant (equally socially engaging, but ignorant about object labels). At test, infants were asked to make an impossible choice—locate a novel referent among two novel objects. When facing epistemic uncertainty—but not at other phases of the procedure—infants selectively referred to the Informant rather than the Non‐Informant. These results show that pre‐verbal infants use social referencing to actively and selectively seek information from social partners as part of their interrogative communicative toolkit. A video abstract of this article can be viewed at https://youtu.be/23dLPsa-fAY
Evaluation of the size of cardiac structures in patients with high body mass index
Authors: Carnevalini Mariana , Deschle Héctor , Amenabar Agustina , Casso Norberto , Gantesti Jessica , Alfie Laura , Torres Bianqui Carolina
Published: January 2020

Aims

Isometric indexation of cardiac structures fails in patients with overweight. The aim of the study was to evaluate the LA indexed volume (LAVOL), left ventricular end‐diastolic diameter (LVEDD), left ventricular mass index (LVMI), and the aortic sinus diameter (AOSD) in healthy subjects with normal and high BMI and find the allometric correction exponent.

Methods

Four hundred and thirty patients without cardiac pathology were analyzed. Patients were divided into groups: Group I BMI < 24.9 187 patients, Group II BMI 25‐29.9 154 patients, Group III BMI 30‐34.9 63 patients, and Group IV 35‐39.9 26 patients. A Doppler echocardiogram was performed. The parameters indexed were compared between groups. When allometric growth was verified, the allometric coefficient was calculated.

Results

Male sex 242 p (56%), mean age: 44.87 ± 13.10 years, better correlation: LAVOL, LV mass, and AOSD with body surface area (BSA) (LAVOL R: .74, R2 .55, LV mass R: .73, R2: 0.53, AOSD R: .57, R2: .35), LVEDD with high (R: .63, R2: .39) were observed. A significant increase was observed in LAVOL and LVMI in the groups with increased BMI. We observed a decrease in the indexed AOSD and a marginal difference between groups in LVEDD. The allometric correction exponent calculated was as follows: LAVOL: 0.96 and for LVMI: 0.97.

Conclusions

Allometric correction is superior to isometric indexation to assess LAVOL and LVMI in obese and overweight patients. Allometric correction would allow differentiating deviations from VOLAI and IMVI attributable to obesity from those attributable to an associated pathology.
The influence of metallothionein treatment and treadmill running exercise on disease onset and survival in SOD1G93A amyotrophic lateral sclerosis mice
Authors: Lewis Katherine E. A. , Bennett William , Blizzard Christopher L. , West Adrian K. , Chung Roger S. , Chuah Meng Inn
Published: January 2020

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterised by the degeneration of motor neurons innervating skeletal muscle. The mechanisms underlying neurodegeneration in ALS are not yet fully elucidated, and with current therapeutics only able to extend lifespan by a matter of months there is a clear need for novel therapies to increase lifespan and patient quality of life. Here, we evaluated whether moderate‐intensity treadmill exercise and/or treatment with metallothionein‐2 (MT2), a neuroprotective protein, could improve survival, behavioural or neuropathological outcomes in SOD1G93A familial ALS mice. Six‐week‐old female SOD1G93A mice were allocated to one of four treatment groups: MT2 injection, i.m.; moderate treadmill exercise; neither MT2 nor exercise; or both MT2 and exercise. MT2‐treated mice survived around 3% longer than vehicle‐treated mice, with this mild effect reaching statistical significance in Cox proportional hazards analysis once adjusted for potential confounders. Mixed model body weight trajectories over time indicated that MT2‐treated mice, with or without exercise, reached maximum body weight at a later age, suggesting a delay in disease onset of around 4% compared to saline‐treated mice. Exercise alone did not significantly increase survival or delay disease onset, and neither exercise nor MT2 substantially ameliorated gait abnormalities or muscle strength loss. We conclude that neither exercise nor MT2 treatment was detrimental in female SOD1G93A mice, and further study could determine whether the mild effect of peripheral MT2 administration on disease onset and survival could be improved via direct administration of MT2 to the central nervous system.
The economic burden of caregiving in epilepsy: An estimate based on a survey of US caregivers
Authors: Hussain Shaun A. , Ortendahl Jesse D. , Bentley Tanya G. K. , Harmon Amanda L. , Gupta Shaloo , Begley Charles E. , Khilfeh Ibrahim , Knoth Russell L.
Published: January 2020

Objective

The burden of caregiving for persons with epilepsy (PWEs) has not been examined previously in the United States. We assessed the clinical impact and direct and indirect economic costs for caregivers of PWEs.

Methods

An internet survey of 500 caregivers of PWEs was conducted from May to July 2015 using a combination of validated instruments and questions designed specifically for this survey. Caregivers were stratified by PWE age (adult/child) and disease severity (low: 0 vs high: 1 + seizures in the prior month). Annual self‐reported direct and indirect costs were reported per caregiver and extrapolated to all US caregivers. The economic burden of caregiving for PWEs was defined as the difference between costs for caregivers and the general population.

Results

Caregivers reported that PWEs averaged 11.4 seizures in the prior month. Eighty percent of respondents were female and the average age was 44.3. Since becoming a caregiver, many reported anxiety (52.8%), depression (41.0%), and insomnia (30.8%). Annual mean direct medical costs for caregivers of children with low vs high seizure frequency were $4344 and $10 162, respectively. Costs for caregivers of adult PWEs were $4936 and $8518. Mean indirect costs associated with caregiving for a child with low vs high seizure frequency were $20 529 and $40 137; those for caregivers of an adult were $13 981 and $28 410. The cost estimates are higher vs the general US population; annual per‐person healthcare utilization costs were $2740 and productivity loss costs were $5015. When extrapolating to the US population of PWE caregivers, annual costs exceeded $62 billion vs $14 billion for the general population, resulting in a caregiver burden of nearly $48 billion.

Significance

The clinical and economic burden of caregivers for PWE were substantial, and greatest for those caring for children with frequent seizures. The impact on caregivers should be considered when estimating the value of interventions that control epilepsy.
Epilepsy‐specific patient‐reported outcome measures of children's health‐related quality of life: A systematic review of measurement properties
Authors: Crudgington Holly , Rogers Morwenna , Morris Hannah , Gringras Paul , Pal Deb K. , Morris Christopher
Published: January 2020

Objective

To identify and appraise published evidence of the measurement properties for epilepsy‐specific patient‐reported outcome measures (PROMs) of children's health‐related quality of life (HRQoL).

Methods

We searched multiple databases for studies evaluating the measurement properties of English‐language epilepsy‐specific PROMs of children's HRQoL. We assessed the methodological quality using the COnsensus‐based Standards for the selection of health Measurement INstruments (COSMIN) guidance. We extracted data about the content validity, construct validity, internal consistency, test‐retest reliability, proxy reliability, responsiveness, and precision, and assessed the measurement properties with reference to standardized criteria.

Results

We identified 27 papers that evaluated 11 PROMs. Methodological quality was variable. Construct validity, test‐retest reliability, and internal consistency were more commonly assessed. Quality of Life in Childhood Epilepsy (QoLCE) questionnaires are parent‐reported and evaluated more than other PROMs; QoLCE‐55 has good and replicated evidence for structural and construct validity and internal consistency. Health‐Related Quality of Life Measure for Children with Epilepsy (CHEQoL) has both child and parent‐reported versions and good evidence of content, structural, and construct validity.

Significance

This review identified two leading candidate epilepsy‐specific PROMs for measuring health‐related quality of life in children. Establishing evidence of the responsiveness of PROMs is a priority to help the interpretation of meaningful change scores.
Three dimensional ultra‐high‐density electro‐anatomical cardiac mapping in horses: methodology
Authors: Van Steenkiste Glenn , De Clercq Dominique , Boussy Tim , Vera Lisse , Schauvliege Stijn , Decloedt Annelies , van Loon Gunther
Published: January 2020

Background

Ultra‐high‐density cardiac mapping allows very accurate characterisation of atrial and ventricular electrophysiology and activation timing.

Objective

To describe the technique and evaluate the feasibility of magnetic electro‐anatomical mapping of the equine heart.

Study design

In vivo experimental method development.

Methods

A mapping system using an 8.5F bidirectional deflectable catheter with a deployable mini‐basket (3–22 mm) containing 64 electrodes divided over eight splines was evaluated. Based upon predefined beat acceptance criteria, the system automatically acquires endocardial electrograms and catheter location information. Electro‐anatomical maps were acquired from four horses in sinus rhythm under general anaesthesia.

Results

All endocardial areas within each chamber could be reached. Access to the left atrium required the use of a deflectable sheath. With the exception of the left atrial map of horse 1, all four chambers in all four horses could be mapped. Optimisation of the beat acceptance criteria led to a reduction in manual correction of the automatically accepted beats from 13.1% in the first horse to 0.4% of the beats in the last horse.

Main limitations

Only a limited number of horses were included in the study.

Conclusion

Ultra‐high‐density 3D electro‐anatomical mapping is feasible in adult horses and is a promising tool for electrophysiological research and characterisation of complex arrhythmias.
Role of neuroimmune circuits and pruritus in psoriasis
Authors: Ayasse Marissa T. , Buddenkotte Jörg , Alam Majid , Steinhoff Martin
Published: January 2020

Psoriasis is a chronic inflammatory skin disease presenting with an array of clinical phenotypes, often associated with pruritus. Environmental and psychological stressors can exacerbate psoriasis symptoms and provoke flares. Recent studies suggest a dysfunctional hypothalamic‐pituitary‐adrenal (HPA) axis in some patients with psoriasis that can result in immune dysregulation. The immune system, in turn, can communicate with the nervous system to induce, maintain or aggravate psoriasis. In the skin, peripheral sensory as well as autonomic nerves control release of inflammatory mediators from dendritic cells, mast cells, T cells or keratinocytes, thereby modulating inflammatory responses and, in case of sensory nerves, pruritus. In response to the environment or stress, cytokines, chemokines, proteases, and neuropeptides fluctuate in psoriasis and influence immune responses as well as nerve activity. Furthermore, immune cells communicate with sensory nerves which control release of cytokines, such as IL‐23, that are ultimately involved in psoriasis pathogenesis. Nerves also communicate with keratinocytes to induce epidermal proliferation. Notably, in contrast to recent years the debilitating problem of pruritus in psoriasis has been increasingly appreciated. Thus, investigating neuroimmune communication in psoriasis will not only expand our knowledge about the impact of sensory nerves in inflammation and pruritus and give new insights into the impact of environmental factors activating neuroimmune circuits or of stress in psoriasis, but may also lead to novel therapies. This review summarizes the relevant literature on the role of neuroimmune circuits, stress and how the central HPA axis and its peripheral equivalent in the skin, impact psoriasis.
TL1A/TNFR2‐mediated mitochondrial dysfunction of fibroblast‐like synoviocytes increases inflammatory response in patients with rheumatoid arthritis via reactive oxygen species generation
Authors: Al‐Azab Mahmoud , Qaed Eskandar , Ouyang Xunli , Elkhider Abdalkhalig , Walana Williams , Li Han , Li Weiping , Tang Yawei , Adlat Salah , Wei Jing , Wang Bing , Li Xia
Published: January 2020

Rheumatoid arthritis (RA) is the major autoimmune destructive disease of joints with a complicated pathogenesis. The contribution of tumor necrosis factor‐like ligand 1A (TL1A) in RA pathogenesis, especially on fibroblast‐like synoviocytes (FLS), has been suggested clinically. The present study investigated the role of TL1A in mitochondrial dysfunction, induced oxidative stress in mitochondria, apoptosis resistance and the inflammatory response in FLS obtained from RA patients (RA‐FLS). RA‐FLS were incubated with TL1A and tumor necrosis factor receptor 2 (TNFR2) antagonist. Respiratory function, mitochondrial membrane potential and respiration associated genes of mitochondria were measured in both TL1A stimulated and non‐stimulated RA‐FLS. Additionally, the effects of TL1A on reactive oxygen species (ROS) production in mitochondria, apoptosis and the inflammatory response in RA‐FLS were also assessed. The role of TL1A in association between ROS generation, especially mitochondrial type and the inflammatory response, was evaluated by measuring inflammation‐related cytokines and signaling pathways using ROS inhibitors, diphenyleneiodonium chloride and Mito‐TEMPO (Sigma‐Aldrich, Miamisburg, OH, USA). We found that TL1A induced mitochondrial dysfunction by weakening mitochondrial respiration and membrane potential, which was blocked by a TNFR2 antagonist. Increased ROS synthesis in impaired mitochondria was observed with MitoSOX (Invitrogen, CA, USA) immunofluorescence staining in TL1A‐stimulated RA‐FLS but inhibited by a TNFR2 antagonist. TL1A influenced apoptosis resistance and inflammatory mediators via TNFR2. Inhibition of mitochondria‐derived ROS compromised the production of inflammatory factors in TL1A‐stimulated RA‐FLS, suggesting that mitochondrial dysfunction mediated by the TL1A/TNFR2 axis might amplify the inflammatory response via regulation of mitochondria‐derived ROS generation. Collectively, our results reveal that TL1A might be involved in making FLS more aggressive in RA pathogenesis via cell respiration interruption.
The re‐emerging pathophysiological role of the cystathionine‐β‐synthase ‐ hydrogen sulfide system in Down syndrome
Authors: Szabo Csaba
Published: January 2020

Down syndrome (DS) is associated with significant perturbances in many morphological and biochemical features. Cystathionine‐β‐synthase (CBS) is one of the key mammalian enzymes that is responsible for the biological production of the gaseous transmitter hydrogen sulfide (H2S). When H2S is overproduced, it can exert detrimental cellular effects, in part due to inhibition of mitochondrial Complex IV activity. An increased expression of CBS and the consequent overproduction of H2S are well documented in individuals with DS. Two decades ago, it has been proposed that a toxic overproduction of H2S importantly contributes to the metabolic and neurological deficits associated with DS. However, until recently, this hypothesis has not yet been tested experimentally. Recent data generated in human dermal fibroblasts show that DS cells overproduce H2S, which, in turn, suppresses mitochondrial Complex IV activity and impairs mitochondrial oxygen consumption and ATP generation. Therapeutic CBS inhibition lifts the tonic (and reversible) suppression of Complex IV: This results in the normalization of mitochondrial function in DS cells. H2S may also contribute to the cellular dysfunction via several other molecular mechanisms through interactions with various mitochondrial and extramitochondrial molecular targets. The current article provides a historical background of the field, summarizes the recently published data and their potential implications, and outlines potential translational approaches (such as CBS inhibition and H2S neutralization) and future experimental studies in this re‐emerging field of pathobiochemistry.