bluuebunny/crossref_metadata_2025 huggingface dataset:
Trial‐based cost‐effectiveness analysis of ultrathin Descemet stripping automated endothelial keratoplasty (UT‐DSAEK) versus DSAEK
Authors: Simons Rob W.P. , Dickman Mor M. , van den Biggelaar Frank J.H.M. , Dirksen Carmen D. , Van Rooij Jeroen , Remeijer Lies , Van der Lelij Allegonda , Wijdh Robert H.J. , Kruit Pieter J. , Nuijts Rudy M.M.A.
Published: April 2019

Purpose

To evaluate the cost‐effectiveness of ultrathin Descemet stripping automated endothelial keratoplasty (UT‐DSAEK) versus standard DSAEK.

Methods

A cost‐effectiveness analysis using data from a multicentre randomized clinical trial was performed. The time horizon was 12 months postoperatively. Sixty‐four eyes of 64 patients with Fuchs’ endothelial dystrophy were included and randomized to UT‐DSAEK (n = 33) or DSAEK (n = 31). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality‐adjusted life years (QALYs) were determined using the Health Utilities Index Mark 3 questionnaire. The main outcome was the incremental cost‐effectiveness ratio (ICER; incremental societal costs per QALY).

Results

Societal costs were €9431 (US$11 586) for UT‐DSAEK and €9110 (US$11 192) for DSAEK. Quality‐adjusted life years (QALYs) were 0.74 in both groups. The ICER indicated inferiority of UT‐DSAEK. The cost‐effectiveness probability ranged from 37% to 42%, assuming the maximum acceptable ICER ranged from €2500–€80 000 (US$3071–US$98 280) per QALY. Additional analyses were performed omitting one UT‐DSAEK patient who required a regraft [ICER €9057 (US$11 127) per QALY, cost‐effectiveness probability: 44–62%] and correcting QALYs for an imbalance in baseline utilities [ICER €23 827 (US$29 271) per QALY, cost‐effectiveness probability: 36–59%]. Furthermore, the ICER was €2101 (US$2581) per patient with clinical improvement in best spectacle‐corrected visual acuity (≥0.2 logMAR) and €3274 (US$4022) per patient with clinical improvement in National Eye Institute Visual Functioning Questionnaire‐25 composite score (≥10 points).

Conclusion

The base case analysis favoured DSAEK, since costs of UT‐DSAEK were higher while QALYs were comparable. However, additional analyses revealed no preference for UT‐DSAEK or DSAEK. Further cost‐effectiveness studies are required to reduce uncertainty.
Perceived Similarity in Multiple Categorisation
Authors: Grigoryan Lusine
Published: April 2019

As the diversity of modern societies becomes more structurally complex, the importance of studying multiple cross‐cutting group memberships increases as well. The present study investigates the causes and consequences of perceived similarity in multiple categorisation settings. In a factorial survey with six ethnic groups in Russia (N = 524 participants, 5,036 observations), this study examines the effects of eight real‐life social categories (ethnicity, religion, gender, age, education level, proficiency in Russian language, job skill level, and immigration background) on perceived similarity and attitudes. The findings show that ingroup membership on each categorisation dimension increases perceived similarity with the target and that high‐status others are evaluated as more similar even by participants who belong to a lower‐status group. Findings also suggest that all judgments of targets fall into two clusters, which can be described as “in‐group‐like” and “out‐group‐like” others. The implications for information processing in image formation are discussed. Finally, path analysis results indicate that participants’ attitudes towards the target person are mediated by perceived similarity for all categories. These findings provide strong evidence for the large explanatory power of perceived similarity in judgments of others when multiple group memberships are salient.
Systematic review with meta‐analysis: Lactobacillus rhamnosus GG for treating acute gastroenteritis in children – a 2019 update
Authors: Szajewska Hania , Kołodziej Maciej , Gieruszczak‐Białek Dorota , Skórka Agata , Ruszczyński Marek , Shamir Raanan
Published: April 2019

Background

Recently, evidence from a large randomised controlled trial (RCT) negated efficacy of Lactobacillus rhamnosus GG for treating acute gastroenteritis in children.

Aim

To review RCTs in which L rhamnosus GG was used to treat acute gastroenteritis in children.

Methods

The Cochrane Library, MEDLINE, and EMBASE databases were searched from May 2013 (end of last search) to January 2019. The primary outcomes were stool volume and duration of diarrhoea.

Results

Eighteen RCTs (n = 4208) were included. Compared with placebo or no treatment, L rhamnosus GG use had no effect on stool volume but was associated with a reduced duration of diarrhoea (15 RCTs, n = 3820, mean difference, MD −0.85 day, 95% CI −1.15 to −0.56). L rhamnosus GG was effective when used at a daily dose of ≥1010 CFU or <1010CFU; however, the latter produced results of borderline significance. L rhamnosus GG was more effective when used in European countries compared with non‐European countries, particularly when considered by region. L rhamnosus GG use was associated with a reduced duration of hospitalisation. One RCT found that L rhamnosus GG had no effect on the total clinical severity score at 14 days after enrolment.

Conclusions

Despite a recent large RCT demonstrating no effect of L rhamnosus GG, current evidence shows that, overall, L rhamnosus GG reduced both the duration of diarrhoea (with a higher impact in European countries) and hospitalisation in inpatients. These findings should be viewed in the context of the high heterogeneity and methodological limitations of the included trials.
Effects of stocking density on oxidative stress status and mammary gland permeability in early lactating dairy cows
Authors: Lin Shi‐xin , Liu Jian‐xin , Wang Kai‐ying , Wang Di‐ming
Published: April 2019

The current study was conducted to investigate the effect of stocking density (SD) on oxidative stress status and mammary gland permeability in early lactating dairy cows. Thirty‐two dairy cows were allocated into 16 blocks, basing on parity, previous milk yield, and body weight, and were then randomly assigned into one of the two treatments as follows: 75% (75SD) and 100% (100SD) SD. The cows were fed with same diet throughout the 8‐week experimental period. The milk yield and milk sample were collected on two consecutive days during the 8‐week experimental period weekly. Plasma samples were collected on fourth and eighth experimental weeks. Raw, energy‐corrected, and 4% fat‐corrected milk yield were significantly higher in 75SD‐cows than that of 100SD‐animals, respectively. The milk somatic cell count was lower in 75SD‐cows than that of 100SD‐animals. The levels of Na+, Na+/K+, bovine serum albumin and plasmin were lower in 75SD‐cows than those of 100SD‐cattle, respectively. The 75SD‐cows had reduced insulin and insulin/glucagon levels but higher prolactin and growth hormone concentrations, compared with those of 100SD‐animals, respectively. In conclusion, compared with low SD‐animals, early lactating cows with higher SD had higher oxidative stress status, which further led to a greater mammary gland permeability.
Pilot study to quantify the time to clear dexamethasone from plasma and urine of adult horses following a single nebulisation
Authors: Symonds NE , Dart AJ , Keledjian J , Lau M Liu , Ennis LC , McIver VC , Tsang AS , Biasutti SA , Jeffcott LB
Published: April 2019

Objective

To quantify the time to clear dexamethasone from plasma and urine of horses following a single nebulisation.

Design

Experimental using six Standardbred mares.

Methods

Dexamethasone sodium phosphate (0.04 mg/kg) diluted in 0.9% sodium chloride was administered as an aerosol using a Flexineb E2® nebuliser. Blood samples (0, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 h) and urine samples (0, 1, 4, 8, 24, 32, 48, 72 and 96 h) were collected for analysis using liquid chromatography mass spectrometry.

Results

Maximum plasma concentrations (tmax) were reached by the earliest detection point (2 h) after nebulisation (0.6–1.8 ng/mL), but was no longer detectable at 48 h. However, in one horse 0.1 ng/mL was found at 96 h after three consecutive readings of 0 ng/mL. The tmaxin urine was reached by the earliest collection point (1 h) after nebulisation (3.2–23.8 ng/mL), but was no longer present in urine at 72 h in five horses, while detectable levels (0.1 ng/mL) were still present at 96 h in one horse.

Conclusions

A single dose of 0.04 mg/kg of DSP administered as an aerosol through a FlexinebE2® mask was no longer detectable in blood at 48 h in six horses tested, but one horse returned a reading of 0.1 ng/mL at 96 h after having no detectable levels. Dexamethasone was not detectable in urine at 72 h in five horses but was detectable at a low concentration (0.1 ng/mL) at 96 h in one horse.
Confirmed case of Pneumocystis pneumonia in a Maltese Terrier × Papillon dog being treated with toceranib phosphate
Authors: Best MP , Boyd SP , Danesi P
Published: April 2019

Case report

A 7‐year‐old female‐neutered Maltese Terrier × Papillon dog was presented with tachypnoea and weight loss following 12 months of therapy with toceranib phosphate for a metastatic, histologically‐low‐grade mast cell tumour.

The dog was diagnosed with Pneumocystis canis based on PCR with supportive clinical, radiographic and cytological findings. No other clinical evidence of immunocompromise was identified through assessment of haematology and immunoglobulin quantification. Clinical signs completely resolved with a short course of potentiated sulfonamides and discontinuation of the toceranib.

Conclusion

To the authors’ knowledge this represents the first case of Pneumocystis in a dog secondary to immunomodulatory drug therapy. It is also the first case of opportunist infection secondary to a tyrosine kinase inhibitor in dogs.
Pharmacodynamics of rituximab on B lymphocytes in paediatric patients with autoimmune diseases
Authors: Pan Shan , Yu Huixin , Surti Ayesha , Cheng Iek , Marks Stephen D. , Brogan Paul A. , Eleftheriou Despina , Standing Joseph F.
Published: April 2019

Aims

Rituximab is a chimeric IgG‐1 monoclonal antibody that depletes B cells, aiding in the treatment of several conditions including autoimmune diseases. It is not licensed for use in children. This study aimed to quantify the B cell‐related pharmacodynamics of rituximab in children with autoimmune disease.

Methods

Routine electronic health record data were collected at a large paediatric tertiary hospital in London, UK. Dosing protocols were either 2 × 750 mg/m2 intravenous infusions of rituximab on days 1 and 15, or 4 × 375 mg/m2 infusions on days 1, 8, 15 and 22. Rituximab pharmacokinetics (PK) were not measured but CD19+ lymphocyte counts were taken before and after rituximab treatment. A dose–response model was constructed describing the life cycle of CD19+ lymphocytes, with rituximab assumed to increase the death rate. Rituximab effect was assumed to decay by first‐order kinetics.

Results

In total, 258 measurements of CD19+ lymphocyte counts were collected from 39 children with 8 autoimmune diseases. The elimination rate constant (% relative standard error) of rituximab effect decay was 0.036 (22.7%) days−1 and CD19+ turnover was 0.02 (41%) days−1 corresponding to half‐lives of 19 and 35 days respectively. Rituximab increased CD19+ death rate 35‐fold, with methotrexate and cyclophosphamide associated with further increases. Simulations suggested that a single infusion of 750 mg/m2 provides similar 6‐month suppression of CD19+ lymphocytes to current dosing.

Conclusions

Rituximab pharmacodynamics (PD) in paediatric autoimmune diseases has been described. Compared with rituximab alone, the additional effect of methotrexate or cyclophosphamide was statistically significant but small.
Pharmacokinetic and pharmacodynamic modelling for renal function dependent urinary glucose excretion effect of ipragliflozin, a selective sodium–glucose cotransporter 2 inhibitor, both in healthy subjects and patients with type 2 diabetes mellitus
Authors: Saito Masako , Kaibara Atsunori , Kadokura Takeshi , Toyoshima Junko , Yoshida Satoshi , Kazuta Kenichi , Ueyama Eiji
Published: April 2019

Aims

To provide a model‐based prediction of individual urinary glucose excretion (UGE) effect of ipragliflozin, we constructed a pharmacokinetic/pharmacodynamic (PK/PD) model and a population PK model using pooled data of clinical studies.

Methods

A PK/PD model for the change from baseline in UGE for 24 hours (ΔUGE24h) with area under the concentration–time curve from time of dosing to 24 h after administration (AUC24h) of ipragliflozin was described by a maximum effect model. A population PK model was also constructed using rich PK sampling data obtained from 2 clinical pharmacology studies and sparse data from 4 late‐phase studies by the NONMEM $PRIOR subroutine. Finally, we simulated how the PK/PD of ipragliflozin changes in response to dose regime as well as patients' renal function using the developed model.

Results

The estimated individual maximum effect were dependent on fasting plasma glucose and renal function, except in patients who had significant UGE before treatment. The PK of ipragliflozin in type 2 diabetes mellitus (T2DM) patients was accurately described by a 2‐compartment model with first order absorption. The population mean oral clearance was 9.47 L/h and was increased in patients with higher glomerular filtration rates and body surface area. Simulation suggested that medians (95% prediction intervals) of AUC24h and ΔUGE24h were 5417 (3229–8775) ng·h/mL and 85 (51–145) g, respectively. The simulation also suggested a 1.17‐fold increase in AUC24h of ipragliflozin and a 0.76‐fold in ΔUGE24h in T2DM patients with moderate renal impairment compared to those with normal renal function.

Conclusions

The developed models described the clinical data well, and the simulation suggested mechanism‐based weaker antidiabetic effect in T2DM patients with renal impairment.
Activism, Bioethics and Academic Research
Authors: Draper Heather
Published: April 2019

This article sketches a taxonomy of the activities in which bioethics academics engage, including activities that may make their own research more impactful, from little or no engagement outside academia to activism or extreme activism. This taxonomy, the first of its kind, may be useful in determining what obligations bioethics academics have in relation to activism and activities that fall short of activism.
Developing a Work‐Ready Social Media Marketing Analytics Course: A Model to Cultivate Data‐Driven and Multiperspective Strategy Development Skills
Authors: Kim Yuna
Published: April 2019

This article reports on an innovative Social Media Marketing Analytics course that was developed to respond to current industry needs for marketing analysts with data‐driven and multiperspective marketing strategy development skills. Teaching approaches, resources, and insights are shared to encourage future development of similar courses.
The effect of remittances on the current account in developing and emerging economies
Authors: Lartey Emmanuel K. K.
Published: April 2019

This paper presents an analysis of the effect of remittances on the current account in developing and emerging economies, incorporating an assessment of the extent to which exchange rate regimes impact the relationship. The main findings suggest that there is a positive effect of remittances on the current account contemporaneously, but that the lagged effect is negative, which could be indicative of the existence of some underlying mechanisms characteristic of the Dutch disease phenomenon. In addition, the results show that a more flexible exchange regime dampens the contemporaneous positive effect that remittances have on the current account. The paper, therefore, asserts that policymakers face trade‐offs pertaining to the use of exchange rate policy in managing the effects of remittances on the current account, which should be given due consideration when such policy choices are made.
Pre‐Frail Multicomponent Training Intervention project for complexity of biological signals, functional capacity and cognition improvement in pre‐frail older adults: A blinded randomized controlled study protocol
Authors: Buto Marcele S S , Fiogbé Elie , Vassimon‐Barroso Verena , Rossi Paulo G , Farche Ana CS , Carnavale Bianca F , Takahashi Anielle CM
Published: April 2019

Aim

Frailty syndrome is related to decreased physiological complexity, functional capacity and cognition. Physical exercise has been suggested to slow down and reverse this syndrome. However, evidence of its effectiveness is not as straightforward as conventionally admitted, as there is a lack of trials with rigorous methodology. The purpose of this study was to describe the Pre‐Frail Multicomponent Training Intervention protocol.

Methods

Cardiovascular, motor control and neuromuscular systems of pre‐frail older adults will be assessed by measuring the complexity of the output of these systems. Functional capacity and cognition will be assessed by specific tools. A 16‐week training protocol will be carried out on three alternate days, with 60‐min sessions, and combining aerobic, muscle strength, flexibility and balance exercises. The objective of this intervention is to improve the cardiovascular, motor control and neuromuscular systems, as well as functional capacity and cognition of pre‐frail older adults. The assessment of these systems will be carried out using gold standard devices.

Results

The results of the present study might allow clinical and functional support for the evaluation of the variables analyzed.

Conclusion

This protocol is easily reproducible and requires low‐cost materials, thus the Pre‐Frail Multicomponent Training Intervention could be a therapeutic strategy for pre‐frail older adults. Geriatr Gerontol Int 2019; 19: 684–689.
Differences in gene expression profiling and biomarkers between histological colorectal carcinoma subsets from the serrated pathway
Authors: García‐Solano José , Turpin‐Sevilla María del Carmen , García‐García Francisco , Carbonell‐Muñoz Rosa , Torres‐Moreno Daniel , Conesa Ana , Conesa‐Zamora Pablo
Published: April 2019

Aims

To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI‐H) both sharing common features (female gender, right‐sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options.

Methods and results

Molecular signatures of SAC and hmMSI‐H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over‐representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll‐like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule‐1 (ICAM1) was more highly expressed in hmMSI‐H, whereas two genes [those encoding calcitonin gene‐related peptide‐receptor component protein and C‐X‐C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings.

Conclusions

Our findings highlight specific functions and genes that provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules.
Potential role of TP63 in apical periodontitis development
Authors: Souza L. C. , Crozeta B. M. , Guajardo L. , Brasil da Costa F. H. , Sousa‐Neto M. D. , Letra A. , Silva R. M.
Published: April 2019

Aim

To investigate the expression of TP63 in apical periodontitis (AP) tissues and the association of single nucleotide polymorphisms (SNPs) in the TP63 gene with AP using a case‐control dataset.

Methodology

Expression of TP63 in human AP lesions (apical abscess, radicular cyst, periapical granuloma) was evaluated using immunohistochemistry. A case‐control association study was performed to assess the association of TP63 polymorphisms in individuals having AP with or without associated pain. Cases were defined as subjects with deep caries and AP (n = 151) and subjects with symptomatic apical periodontitis or acute apical abscess (n = 124). Subjects without AP (n = 169) and asymptomatic (n = 196) were used as controls, respectively. Saliva samples were collected as source of genomic DNA. Twelve SNPs in the TP63 gene were selected for genotyping using Taqman chemistry in real‐time PCR. Data analysis was performed using PLINK software. The Bonferroni method was applied to correct for multiple testing; α ≤ 0.004 indicates significant differences between groups.

Results

TP63 expression was evident in apical abscesses and radicular cysts, while weaker expression was observed in periapical granulomas. Positive expression was observed in mononuclear cells in the granulation tissues of all AP lesions. Regarding the presence of AP, a trend for allelic association was observed for rs16864812 and rs9810322 (P = 0.04) and rs9810322 genotypes were also nominally associated with AP under a dominant model (P = 0.04). When considering the presence of periapical pain, a trend for allelic and genotypic association was observed for rs10155037 (P = 0.03). Haplotypes were also associated with AP and periapical pain (P ≤ 0.05).

Conclusions

Apical periodontitis is a complex multifactorial condition and it is likely that multiple genes and environmental effects may influence its susceptibility, progression or both. TP63 variants may play a role in AP pathogenesis and susceptibility, individually or interactively with other genes. Additional studies in other populations and functional studies are needed to improve understanding of the role of TP63 in AP.
Impact of apical extent of root canal filling on vertical root fracture: a case–control study
Authors: PradeepKumar A. R. , Shemesh H. , van Loveren C. , JothiLatha S. , Shireen F. , VijayaBharathi R. , Kishen A.
Published: April 2019

Aim

To investigate the impact of apical extent of root filling on vertical root fracture (VRF) in a case–control study.

Methodology

Eighty‐six patients (119 roots) diagnosed withVRFin crowned root filled anterior and posterior teeth were selected. The cases were matched individually with control teeth in a ratio of 1:1 for age (±5 years), gender, tooth type, canal instrumentation method, master apical file (MAF) size and taper, technique of canal filling and time period after root filling. All root canals had been prepared using nickel–titanium (NiTi) rotary instruments and filled using the lateral compaction technique. The apical extent of root filling (overfilled to or beyond the radiographic apex or not overfilled and short of the radiographic apex) was recorded as the dependent variable by two individual examiners. Inter‐examiner agreement was obtained using Kappa statistics. Recorded numbers of overfilled and not overfilled canals in cases and controls were analysed using chi‐square tests and conditional logistic regression, and odds ratio was calculated. In addition, the frequency distribution of vertical and cross‐sectional extensions and the course ofVRFswere evaluated.

Results

The mean age of patients withVRFswas 50 ± 10 years with 27 (31%) males and 59 (69%) females. The Kappa score for inter‐observer agreement was 0.832 (P < 0.001). There was a significant difference between cases and controls with respect to apical extent of root filling (P < 0.0001). When compared to roots not overfilled, overfilled roots had 11.5 times higher odds for occurrence ofVRF(OR = 11.5;CI: 4.99 – 26.48). MostVRFs had a complete corono‐apical longitudinal extension and were present bucco‐lingually/palatally.

Conclusion

After matching for age, gender, tooth type,MAFsize and taper, canal filling technique and time period after root filling, root canals filled to or beyond the radiographic apex following lateral compaction had a greater association withVRFthan canals filled short of the radiographic apex.
Pricing decisions with reference price effect and risk preference customers
Authors: Zhao Nenggui , Wang Qiang , Cao Ping , Wu Jie
Published: April 2019

We consider a seller selling a single product in a short period and taking reference price effect into account in the presence of risk preference customers. Customers' demand for the product is closely related to their purchase probability, which is determined by their purchase utility that is contingent on the reference price, selling price, and risk coefficients, through a multinomial logit model. Customers in the market are categorized as three types according to their asymmetry perceptions anchoring on the difference between the reference price and selling price: loss‐averse, gain‐seeking, and loss‐neutral. We first theoretically explore the influences of the reference price, risk coefficients, as well as the numbers of three types of customers on the seller's pricing decisions and profits. Then, we introduce model misspecification and use a computational study to further illustrate the significance of the seller's correct cognition on the customers' risk preference behaviors. We find that customers with higher reference price or lower risk coefficients would urge the seller to increase the optimal price. When there are more loss‐averse customers in the market, markdown is optimal for the seller; whereas markup is optimal for the seller when there are more gain‐seeking customers in the market. In addition, we find that customers' risk preference behaviors are nonnegligible for the seller in making pricing decisions, especially when gain‐seeking customers' risk coefficient is small enough or loss‐averse customers' risk coefficient is large enough.
EPC‐derived exosomes promote osteoclastogenesis through LncRNA‐MALAT1
Authors: Cui Yigong , Fu Shenglong , Sun Dong , Xing Junchao , Hou Tianyong , Wu Xuehui
Published: April 2019

Bone repair involves bone resorption through osteoclastogenesis and the stimulation of neovascularization and osteogenesis by endothelial progenitor cells (EPCs). However, the role of EPCs in osteoclastogenesis is unclear. In this study, we assess the effects of EPC‐derived exosomes on the migration and osteoclastic differentiation of primary mouse bone marrow‐derived macrophages (BMMs) in vitro using immunofluorescence, western blotting, RT‐PCR and Transwell assays. We also evaluated the effects of EPC‐derived exosomes on the homing and osteoclastic differentiation of transplanted BMMs in a mouse bone fracture model in vivo. We found that EPCs cultured with BMMs secreted exosomes into the medium and, compared with EPCs, exosomes had a higher expression level of LncRNA‐MALAT1. We confirmed that LncRNA‐MALAT1 directly binds to miR‐124 to negatively control miR‐124 activity. Moreover, overexpression of miR‐124 could reverse the migration and osteoclastic differentiation of BMMs induced by EPC‐derived exosomes. A dual‐luciferase reporter assay indicated that the integrin ITGB1 is the target of miR‐124. Mice treated with EPC‐derived exosome‐BMM co‐transplantations exhibited increased neovascularization at the fracture site and enhanced fracture healing compared with those treated with BMMs alone. Overall, our results suggest that EPC‐derived exosomes can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors through LncRNA‐MALAT1.
Periodontal status correlates with anti‐citrullinated protein antibodies in first‐degree relatives of individuals with rheumatoid arthritis
Authors: Loutan Lucie , Alpizar‐Rodriguez Deshire , Courvoisier Delphine S. , Finckh Axel , Mombelli Andrea , Giannopoulou Catherine
Published: April 2019

Aim

To evaluate periodontal status in first‐degree relatives of patients with rheumatoid arthritis (FDR‐RA) and detect correlation with the presence of anti‐citrullinated protein antibodies (ACPAs).

Materials and Methods

Rheumatologic status and periodontal status were evaluated in a nested case–control study of FDR‐RA with no diagnosis of RA at enrolment. The following parameters were assessed in 34 ACPA‐positive (ACPA+) and 65 ACPA‐negative (ACPA−) subjects: gingival index (GI), plaque index (PI), probing depth (PD), bleeding on probing (BOP) and clinical attachment level (CAL). We compared the two groups using conditional logistic regression.

Results

In ACPA+ individuals, the mean, PD, BOP, CAL and number of sites per person with PD > 4 mm and BOP were significantly higher compared to the ACPA‐ group. All ACPA+ subjects had periodontitis: 44.1% presenting moderate and 47.1% severe periodontitis. ACPA‐ subjects had mainly mild (30.8%) and moderate (27%) periodontitis, differences being significantly different for both moderate periodontitis (p = 0.001) and severe periodontitis (p < 0.001). In multivariable analyses, ACPA status (p = 0.04) and age (p = 0.002) were significantly and independently associated with periodontal conditions.

Conclusion

High prevalence and severity of periodontitis in FDR‐RA was associated with seropositivity to ACPAs. This further strengthens the hypothesis that periodontitis may be a risk factor in the development of RA.
Predictors for tooth loss in periodontitis patients: Systematic review and meta‐analysis
Authors: Helal Omar , Göstemeyer Gerd , Krois Joachim , Fawzy El Sayed Karim , Graetz Christian , Schwendicke Falk
Published: April 2019

Aim

A range of predictors for tooth loss in periodontitis patients have been reported. We performed a systematic review and meta‐analysis to assess the consistency and magnitude of any association between a total of 12 predictors and tooth loss.

Materials and Methods

Medline/Embase/Central were searched for longitudinal studies investigating the association between predictors and tooth loss in periodontitis patients. Random‐effects meta‐analysis was performed, and study quality assessed.

Results

Twenty studies (15,422 patients, mean follow‐up: 12 years) were included. The mean annual tooth loss/patient was 0.12 (min./max: 0.01/0.36). Older patients (n = 8 studies; OR: 1.05, 95% CI: 1.03–1.08/year), non‐compliant ones (n = 11; 1.51, 1.06–2.16), diabetics (n = 7; 1.80, 1.26–2.57), those with IL‐1‐polymorphism (n = 3; 1.80; 1.29–2.52) and smokers (n = 15; 1.98, 1.58–2.48) had a significantly higher risk of tooth loss. Teeth with bone loss (n = 3; 1.04, 1.03–1.05/%), high probing pocket depth (n = 6; 3.19, 1.70–5.98), mobility (n = 4; 3.71, 1.65–8.38) and molars (n = 4; 4.22, 2.12–8.39), especially with furcation involvement (n = 5; 2.68, 1.75–4.08) also showed higher risks. Gender (n = 16; 0.95, 0.86–1.05) and endodontic affection (n = 3; 3.62, 0.99–13.2) were not significantly associated with tooth loss.

Conclusions

Older, non‐compliant, smoking or diabetic patients, and teeth with bone loss, high probing pocket depth, mobility, or molars, especially with furcation involvement showed higher risks of tooth loss.
The evolution of healthy skin to acne lesions: a longitudinal, in vivo evaluation with reflectance confocal microscopy and optical coherence tomography
Authors: Manfredini M. , Bettoli V. , Sacripanti G. , Farnetani F. , Bigi L. , Puviani M. , Corazza M. , Pellacani G.
Published: April 2019

Background

Comedogenesis is defined as the process of the development of a new comedo, which is of great importance for the understanding of acne.

Objective

To evaluate the formation and evolution of acne lesions from clinically unaffected skin of patients with mild–moderate acne to characterize the morphological changes and natural resolution by means of in vivo reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D‐OCT).

Methods

Ten patients with mild–moderate acne, not assuming any topical or systemic therapy, comprised between 12 and 30 years of age, were recruited. A target area of 4 × 4 mm of the face, without acne lesions at baseline, was selected. A set of standardized clinical pictures, RCM and D‐OCT images were acquired weekly for 6 weeks and evaluated.

Results

Seventy full sets of clinical, RCM and D‐OCT images were analysed. The appearance of acne lesion is preceded by an increase of large bright follicles in the area corresponding to infundibular keratinization, followed by increment of inflammation parameter, such as increased of small bright cells upon RCM and vascular network upon D‐OCT, which return to normal after the resolution of acute inflammation.

Conclusion

Acne skin dynamics is complex and seems characterized by the early increase in the number of dysmorphic pilosebaceous units and the hyperkeratinization of the acroinfundibulum of the pilosebaceous duct prior to the occurrence of inflammatory events around the follicle. The processes of hyperkeratinization and inflammatory phenomena may generate a pathologic vicious cycle, which characterizes acne through progressive worsening and a self‐sustainment mechanism.
Associations between electroencephalography power and Alzheimer's disease in persons with Down syndrome
Authors: Musaeus C. S. , Salem L. C. , Sabers A. , Kjaer T. W. , Waldemar G.
Published: April 2019

Background

It is complicated to diagnose dementia in persons with Down syndrome (DS). Older studies have, however, demonstrated low‐frequency activity in electroencephalography (EEG) in persons with concurrent DS and Alzheimer's disease (DS‐AD). The aim of this study was to examine whether it was possible to identify AD‐associated changes (increased high‐frequency power and decreased low‐frequency power) in persons with DS‐AD compared with DS.

Methods

We included 21 persons with DS‐AD and 16 with DS without cognitive deterioration assessed by the informant‐based Dementia Screening Questionnaire in Intellectual Disability. EEG was recorded for all participants. Absolute power for each electrode and global power were calculated for all frequency bands for both eyes open and eyes closed.

Results

For global power in the eyes closed condition, we found an increased global slow‐frequency activity and a decreased global high‐frequency activity in DS‐AD compared with DS. In addition, we found a significant difference in the global alpha/delta ratio with the largest difference found for global alpha power in DS‐AD compared with DS.

Conclusions

In the current study, we found that changes known to be associated with AD could also be identified when comparing DS‐AD with DS using quantitative EEG. In general, these findings suggest that EEG might be a useful tool in diagnosing AD in persons with DS, but larger studies are needed.
Simultaneous recovery of both bright and dim structures from noisy fluorescence microscopy images using a modified TV constraint
Authors: XIAO C. , SMITH Z.J. , CHU K.
Published: April 2019

The quality and information content of biological images can be significantly enhanced by postacquisition processing using deconvolution and denoising. However, when imaging complex biological samples, such as neurons, stained with fluorescence labels, the signal level of different structures can differ by several orders of magnitude. This poses a challenge as current image reconstruction algorithms are focused on recovering low signals and generally have sample‐dependent performance, requiring tedious manual tuning. This is one of the main hurdles for their wide adoption by nonspecialists. In this work, we modify the general constrained reconstruction method (in our case utilizing a total variation constraint) so that both bright and dim structures can drive the deconvolution with equal force. In this way, we can simultaneously obtain high‐quality reconstruction across a wide range of signals within a single image or image sequence. The algorithm is tested on both simulated and experimental data. When compared with current state‐of‐art algorithms, our algorithm outperforms others in terms of maintaining the resolution in the high‐signal areas and reducing artefacts in the low‐signal areas. The algorithm was also tested on image sequences where one set of parameters are used to reconstruct all images, with blind evaluation by a group of biologists demonstrating a marked preference for the images produced by our method. This means that our method is suitable for batch processing of image sequences obtained from either spatial or temporal scanning.

Lay Description

Fluorescence microscopy images of complex biological samples contain a wide range of signal levels. This signal variation leads current reconstruction algorithms, which aim to enhance the quality of the raw images, to have sample‐dependent performance. In this work, we design a new optimization that allows the reconstruction to “pay equal eqattention to” both bright and dim structures. In this way, we can simultaneously recover both bright and dim structures within a single image or image sequence, as validated when the algorithm was quantitatively tested on both simulated and experimental data. When our method was evaluated alongside current state of art algorithms by a group of biologists, our algorithm was considered qualitatively superior.
Maturation of the human foetal basioccipital: quantifying shape changes in second and third trimesters using elliptic Fourier analysis
Authors: Niel Mélissa , Chaumoître Kathia , Corny Julien , Lalys Loïc , Adalian Pascal
Published: April 2019

During prenatal development, the brain is considered the best maturation criterion for the estimation of foetal physiological age, regardless of the conditions of pregnancy. Unfortunately, the brain lyses very quickly after death, but fortunately, the brain also has a major influence over osseous structures of the cranial base during development. Therefore, we considered the osseous structures of the cranial base potential indirect maturation indicators of foetal age. Because of its early formation and robustness, the basioccipital is a cranial base bone that is often used for studies in biological anthropology. Studies generally use conventional morphometry and bone size ratio to highlight morphological changes occurring during the foetal period and to create age estimation methods. These methods usually define thresholds beyond which the morphology of the basioccipital changes, but do not fully consider the form that might be valuable precisely to visualize its development or improve age estimation methods. Using geometric morphometric methods, the present study aims to analyse the development of the basioccipital during the second and third trimesters of foetal life by quantifying and visualizing shape changes in the inferior view. Basioccipital shapes are used as direct indicators of the maturation of the cranial base and as indirect indicators of the maturation of the brain and, by extension, the whole body. A sample of 221 anonymized computed tomographic (CT) scans of normal foetuses, ranging from 18 to 41 gestational weeks (GW), was used. Elliptic Fourier analysis (EFA) was used to quantify the basioccipital outline, and maturation stages were established to visualize shape changes with a principal component analysis. Our study allowed us precisely to quantify and continuously visualize shape changes occurring during prenatal life. Additionally, this study provides the first evidence of two distinct linear shape trajectories of the basioccipital. Foetuses aged between 18 and 26GWhave a rapid shape change with well‐individualized stages, whereas shape changes are less visible in the second trajectory (27–41GW). Furthermore, intra‐stage shape variation is higher for the basioccipital at the beginning of the second and third trimesters than at the first trimester. By using geometric morphometric methods andEFA, this study shows that it was possible to go beyond classical methods. Indeed, the developed methodology enabled the first quantification of the overall shape changes of the basioccipital between gestational ages. The morphological shape changes throughout the foetal period can be useful for anthropological studies and provide new perspectives for immature age estimation methods.
Caucasian endemic medicinal and nutraceutical plants: in-vitro antioxidant and cytotoxic activities and bioactive compounds
Authors: Manukyan Artur , Lumlerdkij Natchagorn , Heinrich Michael
Published: April 2019

Objectives

In order to assess traditional claims about the therapeutic potential of Caucasian endemic medicinal plants and to select plants for phytochemical research, nine plant species were selected and assessed for their in-vitro antioxidant and cytotoxic activities. The metabolite profiles of some priority plants were analysed.

Methods

Antioxidant effects were assessed using the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) system, lipid peroxidation and Folin–Ciocalteu methods. Cytotoxic activities were examined against human liver cancer cells (HepG2) using the Alamar Blue assay. Terpenoids of selected species were analysed by GC and GC-MS. Polyphenols were separated by HPLC.

Key findings

Thymus transcaucasicus, Heracleum transcaucasicum, Ribes armenum, Crataegus armena showed most promising antioxidant activity in ABTS model system. Moreover, Rubus takhtadjanii, C. armena, T. transcaucasicus showed a high level of antioxidant activity by inhibiting lipid peroxidation. C. armena and T. transcaucasicus expressed high-to-moderate cytotoxicity against HepG2 cells. The main terpenoids and polyphenols of Centaurea hajastana, C. armena and T. transcaucasicus were quantified.

Conclusions

This study provides in-vitro data relevant for assessing the use of Caucasian endemic medicinal plants, most importantly C. armena and T. transcaucasicus as traditional antioxidant supplements and potential anticancer remedies. Metabolite profiles of some lead plants showed the nature of bioactive compounds of medical interest.
Preliminary results on the association with feeding and recovery length in equine colic patients after laparotomy
Authors: Valle Emanuela , Giusto Gessica , Penazzi Livio , Giribaldi Marzia , Bergero Domenico , Fradinho Maria João , Lamas Luís Ressano Garcia P. , Gandini Marco
Published: April 2019

Colic is a serious disease for horses and the nutritional management of postoperative colic patients is an extremely important field. The aim of this retrospective study was to analyse the different factors, especially related to nutritional management, that may be associated with recovery length during hospitalization after a surgical intervention for colic, using a multivariate model. Data were collected from the records of horses presented to two hospitals and undergoing surgery for colic. The length (days) of recovery was the outcome of interest and was taken into account as a reference parameter (short, medium, long). The parameters collected (patient details, preoperative clinical and laboratory examinations, postoperative parameters and post‐surgery nutritional parameters) were subjected to multivariate analysis (MCA and PCoA). A ranking class dataset was used to calculate Kendall's tau correlation of the length of recovery with respect to other parameters. Descriptive statistic to identify differences in the recovery length among groups (Kruskal–Wallis and Dunn's Multiple Comparison Test) was also performed. p value was set at < 0.05. Groups were not different in preoperative clinical parameters (BCS, PCV, total protein), postoperative parameters (time to 1st defecation, time to the end of IV fluid therapy and time to first water drinking, anaesthesia) and patient details (age). The comparison among groups revealed differences on the post‐surgical nutritional parameters. Horses with short recovery consumed higher % of DM as forages in the 24 hr compared with the horses that have a long recovery and reach the minimum DM intake in a shorter period. Both Kendall and MCA analysis confirmed that the time to first feeding had a positive association with the length of recovery. Only 37 horses undergoing colic surgery were included in the study. From a clinical standpoint, this study has shown which nutritional parameters are associated with short recovery.
Guideline for Thoracolumbar Pedicle Screw Placement Assisted by Orthopaedic Surgical Robot
Authors: Tian Wei , Liu Ya‐jun , Liu Bo , He Da , Wu Jing‐ye , Han Xiao‐guang , Zhao Jing‐wei , Fan Ming‐xing ,   Technical Committee on Medical Robot Engineering of Chinese Society of Biomedical Engineering,   Technical Consulting Committee of National Robotic Orthopaedic Surgery Application Center
Published: April 2019

The pedicle screw placement procedure is the most commonly used technique for spinal fixation and can provide reliable three‐column stabilization. Accurate screw placement is necessary in clinical practice. To avoid screw malposition, which may decrease the stiffness of the screw‐rod construct or increase the likelihood of neural and vascular injuries, the surgeons must fully understand the regional anatomy. Deformities, such as scoliosis, kyphosis or congenital anomalies, may complicate the application of the pedicle screw placement technique and increase the chance of screw encroachments. Incidences of pedicle screw malposition vary in different districts and hospitals and with surgeons and techniques. Today, the minimally invasive spinal surgery is well developed. However, the narrow corridors and limited views for surgeons increase the difficulty of pedicle screw placement and the possibility of screw encroachment. Evidenced by previous studies, robotic surgery can provide accurate screw placement, especially in settings of spinal deformities, anatomical anomalies, and minimally invasive procedures. Based on the consensus of consultant specialists, the literature review and our local experiences, this guideline introduces the robotic system and describes the workflow of robot‐assisted procedures and the precautions to take during procedures. This guideline aims to outline a standardized method for robotic surgery for thoracolumbar pedicle screw placement.