bluuebunny/crossref_metadata_2025 huggingface dataset:
Once‐weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9‐GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm™ trials
Authors: Oldenburg Johannes , Carcao Manuel , Lentz Steven R. , Mahlangu Johnny , Mancuso Maria Elisa , Matsushita Tadashi , Négrier Claude , Clausen Wan Hui Ong , Ehrenforth Silke , Young Guy
Published: September 2018

Introduction

Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half‐life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products.

Aim

To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9‐GP), using pooled data, with a focus on—but not limited to—prophylaxis at 40 IU/kg.

Methods

N9‐GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once‐weekly intravenous dosing.

Results

In total, 115 previously treated patients were exposed to N9‐GP. Of 54 patients (47%) treated with N9‐GP 40 IU/kg once‐weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once‐weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady‐state trough levels with N9‐GP 40 IU/kg once‐weekly were ≥15% overall; 27.3% in adolescents and adults.

Conclusion

N9‐GP 40 IU/kg once‐weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9‐GP may provide a new treatment option for preventing bleeding in haemophilia B patients.
Impact of intermediate‐dose prophylaxis on progression of haemarthropathy in patients with severe haemophilia A: A 10‐year, single‐centre experience in Korea
Authors: Kim Ju Y. , Lee Da J. , Chun Tong J. , You Chur W.
Published: September 2018

Aim

To determine the impact of 10‐year intermediate‐dose prophylaxis on haemarthropathy progression in patients with severe haemophilia A (SHA).

Methods

Prophylactic treatment with intermediate dose was given maximally for 10 years to 42 patients with SHA in a haemophilia treatment centre in Korea. Patients were divided into three groups based on prophylactic treatment started age: 1‐10 (group A’), 11‐20 (group B’), and ≥21 (group C’). Average annual increase of Pettersson score (P‐score) was compared between the treatment groups.

Results

Average ages and P‐scores at initiation of prophylaxis were 4.65±3.43 years and 2.09±3.25, 16.13±1.73 years and 7.37±4.38, and 28.33±7.25 years and 12.33±6.50 for groups A’, B’, and C’. Average annual increase of P‐score in groups A’, B’, and C’ was 0.039±0.11, 0.063±0.123, and 0.078±0.124. Assuming that intermediate‐dose prophylaxis started at the average age, P‐score and annual increase of P‐score would be the average values of each group; it would thus take 210 and 46.5 years to reach –2SD of the average critical level of haemarthropathy (The level of haemarthropathy (P‐score 13.0 ± 2.7) above which there is a significant impact on quality of life in Korean) in groups A’ and B’. However, it would take 55 and 15.75 years if the annual P‐score increase were +2SD of the average value in groups A’ and B’.

Conclusion

Intermediate‐dose prophylaxis for patients with SHA in Korea would maintain arthropathy below the critical level for most of the patients’ lifetime when started before adolescence. However, this would not be achieved in some adolescent patients with rapid progression of arthropathy and in most adult patients.
Endodontic pathogens possess collagenolytic properties that degrade human dentine collagen matrix
Authors: Marashdeh M. Q. , Gitalis R. , Lévesque C. , Finer Y.
Published: September 2018

Aim

To measure collagenolytic protease activity from Enterococcus faecalis and Micrococcus luteus and their ability to degrade human dentinal collagen.

Methodology

Proteases activity of E. faecalis ATCC 29212, ATCC 47077 and M. luteus towards generic and specific human matrix metalloproteinase (MMP) substrates was measured using a fluorimetric assay. The ability of the bacteria to degrade dentinal collagen was tested by quantifying the amount of hydroxyproline released into the media following incubation of the bacteria or heat‐inactivated bacteria (HIN) with demineralized human dentine samples for 24 h and by scanning electron microscopy (SEM). Multifactorial anova and Tukey's post hoc test were used to analyse the data (P < 0.05).

Results

All strains had MMP‐like activities, but with different substrate affinity; E. faecalis ATCC 29212, ATCC 47077 and M. luteus had the greatest affinity towards MMP‐8 (7.75 ± 0.88 μmol L−1/3 × 106 CFU), MMP‐9 (33.86 ± 5.16 μmol L−1/3 × 106 CFU) and generic MMP (26.08 ± 4.48 μmol L−1/3 × 106 CFU), respectively. The amount of hydroxyproline released from demineralized dentine was similar (P > 0.05) for the three strains (range 1.8 ± 0.17 to 2.38 ± 0.39 μg 50 μL−1) and was significantly higher (P < 0.001) compared to their HIN counterparts (0.61 ± 0.22 μg 50 μL−1). SEM revealed increased collagen network degradation after incubation with bacteria versus HIN.

Conclusions

Endodontic pathogens possess collagenolytic protease properties that enable them to degrade dentinal collagen, potentially compromising the restoration‐tooth and sealer‐tooth interfaces. These collagenolytic protease properties could facilitate the migration of pathogenic bacteria into the root canal system and explain in part their role in root canal infections.
Cutaneous leishmaniasis in Sri Lanka: effect on quality of life
Authors: Refai Wardha F. , Madarasingha Nayani P. , Sumanasena Buthsiri , Weerasingha Sudath , Fernandopulle Rohini , Karunaweera Nadira D.
Published: September 2018

Background

The quality of life in many patients is affected by skin lesions. Cutaneous leishmaniasis (CL), the commonest form of leishmaniasis, is no exception. In Sri Lanka, CL is an emerging parasitological condition with over 3,000 cases within the last decade. Lesions are often seen on exposed parts of the body which may cause social stigma, and hence a study was done to assess the changes in quality of life of CL patients.

Method

A total of 294 patients (200 civilians and 94 army personnel) answered a previously validated Sinhala self‐administered Dermatology Life Quality Index (DLQI) questionnaire and an interviewer‐administered questionnaire.

Results

From the majority of the civilian population, 47% had no effect on their quality of life due to CL lesions, 33.5% were affected in a small way, 12.5% were affected moderately, 6.5% suffered in a large way, and 0.5% (one patient) were extremely affected due a large ulcerative lesion being on the face. The effect on quality of life was negligible in the majority of army patients as well (35.1% no effect, 31.9% small effect), with a few patients affected moderately and very largely (22.3 and 10.6%, respectively). The most affected domain in patients was symptoms and feeling 1.27 ± 1.400 (mean ± SD), and the least was the relationships domain 0.27 ± 0.625.

Conclusion

CL does not seem to affect the quality of life in the majority of Sri Lankan patients when compared to CL in other parts of the world or other skin diseases.
The Integrated Approach to Teaching Visual Art in After‐School Activity Classes
Authors: Blagoeva Nadezda Vladimirova , Karppinen Seija , Kairavuori Seija
Published: September 2018

The present article discusses the possibilities of interdisciplinary integration for teaching art to primary‐school students in after‐school activities. Integrated teaching, as one of the ways for putting into practice the socioconstructivist approach to learning and the theory of the guided construction of knowledge, is used as a basis for conceiving and implementing the two projects described in the empirical part of the article. The research questions, addressed here, aim at finding out how a project‐based approach and the knowledge gained in school and through the students’ individual experiences can be applied pedagogically in after‐school art activities. To achieve the aims of the study a two‐cycle action research was conducted where the integrated teaching was viewed as a developmental spiral, in which the insights, experiences and results gained from the first project fed into the planning and realisation of the second one. The outcomes of the two projects suggest that the integrated presentation of teaching material enhances the students’ learning abilities to make associative connections between the different subjects, to transfer their skills from one project into another, and to apply their knowledge from one subject area to another by processing various sources of visual or verbal information in their creation of artworks. The two projects have proven empirically the validity and educational relevance of the integrated approach to teaching art, and the usefulness of the ideas in the New Finnish Core Curriculum for the holistic development of the child in the complexity of today's world.
Revealing Students’ Ethical Awareness during Problem Framing
Authors: Gray Colin M.
Published: September 2018

Expert designers determine what problem needs to be solved by creating a frame that allows the identification of potential solutions. However, it is unclear how students learn to generate these frames effectively, particularly in relation to ethical decision‐making and selecting appropriate constraints. In this study, undergraduate and graduate industrial design students at a large Midwestern United States university participated in a one‐day workshop that focused on designing products for natives of sub‐Saharan Africa to sell in their home nations. Participants (n=100) worked in 21 teams to generate a range of constraints and problem statements while being scaffolded by instructions, research materials and worksheets. Teams struggled to identify specific use contexts and users, even though these elements were present in relatively complex form in provided research materials. Students appeared to build distance between their own experiences and that of users they were designing for, leading to little awareness of the ethical and normative commitments that were reified in their problem statements and solutions. Implications for the explicit development of an ethically aware design character in design education are considered.
Drawing and the Aestheticisation of the Human Figure by Four‐ to Ten‐Year‐Old Botswana Children: Implications for Pedagogy
Authors: Mannathoko Magdeline Chilalu , Mamvuto Attwell
Published: September 2018

Drawing is one of children's modes of communication which has recently excited academic inquiry in non‐Western cultures. It is the means through which children express their fears, desires, anxieties and conception of phenomena. This study investigated drawings by four‐ to ten‐year‐old Botswana children in response to the human figure as an aesthetic object. The methodology involved observing a sample of forty purposively selected children engaged in the drawing process and analysing their visual productions in addition to conversational talk about their art. The study found that the human figure was the dominant aesthetic subject across ages represented in both conventionalised form and personalised imagery. Older children showed interest in culture specific imagery and demonstrated mastery of occlusion and depth cues, while four‐year‐old children had limited spatial awareness. The study also found that children demonstrated gradual improvement of drawing skills with age. There was no significant difference in drawing competence between sexes. Pedagogical implications are suggested to scaffold children through the stages of art development.
Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3
Authors: Park Nam‐Sook , Park Yu‐Kyoung , Ramalingam Mahesh , Yadav Anil Kumar , Cho Hyo‐Rim , Hong Victor Sukbong , More Kunal N. , Bae Jae‐Hoon , Bishop‐Bailey David , Kano Junko , Noguchi Masayuki , Jang Ik‐Soon , Lee Kyung‐Bok , Lee Jinho , Choi Jong‐Soon , Jang Byeong‐Churl
Published: September 2018

Meridianin C is a marine natural product known for its anti‐cancer activity. At present, the anti‐tumour effects of meridianin C on oral squamous cell carcinoma are unknown. Here, we investigated the effect of meridianin C on the proliferation of four different human tongue cancer cells, YD‐8, YD‐10B, YD‐38 and HSC‐3. Among the cells tested, meridianin C most strongly reduced the growth of YD‐10B cells; the most aggressive and tumorigenic of the cell lines tested. Strikingly, meridianin C induced a significant accumulation of macropinosomes in the YD‐10B cells; confirmed by the microscopic and TEM analysis as well as the entry of FITC‐dextran, which was sensitive to the macropinocytosis inhibitor amiloride. SEM data also revealed abundant long and thin membrane extensions that resemble lamellipodia on the surface of YD‐10B cells treated with meridianin C, pointing out that meridianin C‐induced macropinosomes was the result of macropinocytosis. In addition, meridianin C reduced cellular levels of Dickkopf‐related protein‐3 (DKK‐3), a known negative regulator of macropinocytosis. A role for DKK‐3 in regulating macropinocytosis in the YD‐10B cells was confirmed by siRNA knockdown of endogenous DKK‐3, which led to a partial accumulation of vacuoles and a reduction in cell proliferation, and by exogenous DKK‐3 overexpression, which resulted in a considerable inhibition of the meridianin C‐induced vacuole formation and decrease in cell survival. In summary, this is the first study reporting meridianin C has novel anti‐proliferative effects via macropinocytosis in the highly tumorigenic YD‐10B cell line and the effects are mediated in part through down‐regulation of DKK‐3.
A four‐gene‐based prognostic model predicts overall survival in patients with hepatocellular carcinoma
Authors: Long Junyu , Zhang Lei , Wan Xueshuai , Lin Jianzhen , Bai Yi , Xu Weiyu , Xiong Jianping , Zhao Haitao
Published: September 2018

With the development of new advances in hepatocellular carcinoma (HCC) management and noninvasive radiological techniques, high‐risk patient groups such as those with hepatitis virus are closely monitored. HCC is increasingly diagnosed early, and treatment may be successful. In spite of this progress, most patients who undergo a hepatectomy will eventually relapse, and the outcomes of HCC patients remain unsatisfactory. In our study, we aimed to identify potential gene biomarkers based on RNA sequencing data to predict and improve HCC patient survival. The gene expression data and clinical information were acquired from The Cancer Genome Atlas (TCGA) database. A total of 339 differentially expressed genes (DEGs) were obtained between the HCC (n = 374) and normal tissues (n = 50). Four genes (CENPA, SPP1, MAGEB6 and HOXD9) were screened by univariate, Lasso and multivariate Cox regression analyses to develop the prognostic model. Further analysis revealed the independent prognostic capacity of the prognostic model in relation to other clinical characteristics. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the prognostic model. Then, the prognostic model and the expression levels of the four genes were validated using the Gene Expression Omnibus (GEO) dataset. A nomogram comprising the prognostic model to predict the overall survival was established, and internal validation in the TCGA cohort was performed. The predictive model and the nomogram will enable patients with HCC to be more accurately managed in trials testing new drugs and in clinical practice.
Practitioner experiences from the structured implementation of evidence‐based practice in primary care physiotherapy: A qualitative study
Authors: Carlfjord Siw , Nilsing‐Strid Emma , Johansson Kajsa , Holmgren Theresa , Öberg Birgitta
Published: September 2018

Rationale, Aims, and Objectives

To provide best available care, the practitioners in primary health care (PHC) must have adequate knowledge about effective interventions. The implementation of such interventions is challenging. A structured implementation strategy developed by researchers at Linköping University, Sweden, was used for the implementation of an evidence‐based assessment and treatment programme for patients with subacromial pain among physiotherapists in PHC. To further develop strategies for implementation of evidence‐based practices, it was deemed important to study the implementation from the practitioners' perspective. The aim of this study was to explore the practitioners' experiences from the implementation.

Methods

A qualitative design with focus group discussions was applied. The implementation in terms of perceptions of process and outcome was evaluated by focus group discussions with, in total, 16 physiotherapists in the target group. Data were analysed using the method qualitative content analysis.

Results

The components of the strategy were viewed positively, and the applicability and evidence base behind the programme were appreciated. The programme was perceived to be adopted, and the practitioners described a changed behaviour and increased confidence in handling patients with subacromial pain. Both patient‐ and provider‐related challenges to the implementation were mentioned.

Conclusions

The practitioners' experiences from the implementation were mainly positive. A strategy with collaboration between academy and practice, and with education and implementation teams as facilitators, resulted in changes in practice. Critical voices concerned interprofessional collaboration and that the programme was focused explicitly on the shoulder, not including other components of physical function.
Appearance‐based vs health‐based sun protective messages: A randomized, double‐blind controlled study
Authors: Cheng Judy , Widjajahakim Rafael , Rajanala Susruthi , B. C. Maymone Mayra , Secemsky Eric , Vashi Neelam A.
Published: September 2018

Background

Appearance‐based messages have shown promise in improving sun protection habits among Caucasians but have scarcely been investigated in Hispanic populations.

Objective

To compare the effectiveness of appearance‐based vs health‐based messages in an ethnic patient population, where hyperpigmentation disorders are prevalent and often cosmetically concerning.

Methods

One hundred thirty‐seven patients were randomized to receive images of (a) skin cancer, (b) hyperpigmentation, or (c) wrinkles. Analysis of variance tests for repeated measures were used to estimate the effects of the different stimuli on participants’ knowledge and intention to sun protect.

Results

Appearance‐based interventions were more effective in improving intentions to sun protect among both Hispanics and non‐Hispanic Whites (P < 0.05). They were furthermore more effective among younger patient populations (≤40 years old) and patients who thought that a tanned appearance is attractive (P < 0.05).

Conclusions

Appearance‐based photos of sun damage were more effective than health‐based messages among Hispanics, younger patient populations, and those who find tanned appearances to be attractive.
Ectopic pregnancy following oral levonorgestrel emergency contraception use
Authors: Kitani Yohei , Ishiguro Tatsuya , Kobayashi Akiko , Tamura Ryo , Ueda Haruka , Adachi Sosuke , Nishikawa Nobumichi , Sekine Masayuki , Enomoto Takayuki
Published: September 2018

Levonorgestrel is used worldwide as an emergency oral contraceptive. There have been occasional reports of ectopic pregnancy after oral levonorgestrel use. We present a case of ectopic tubal pregnancy after the use of oral levonorgestrel as an emergency contraceptive in a 37‐year‐old woman with a history of treatment for Chlamydia trachomatis infection. She conceived after sexual intercourse on menstrual day 14 of the first menstrual cycle following a normal delivery. After salpingectomy for this right tubal pregnancy, her following pregnancy was an ectopic pregnancy in the contralateral tube, which was treated with laparoscopic salpingectomy. Histopathological examination revealed endometriosis. We should be aware of ectopic pregnancy even after emergency contraceptive use, especially in patients with risk factors, such as Chlamydia infection and endometriosis. Because the efficacy of levonorgestrel decreases after ovulation, we should check the stage of the cycle before prescription.
Chlorophyll a fluorescence imaging of soya bean leaflets infected by Corynespora cassiicola
Authors: Fortunato Alessandro A. , Debona Daniel , Aucique‐Pérez Carlos E. , Fialho Corrêa Emerson , Rodrigues Fabrício A.
Published: September 2018

Considering the importance of target spot, caused by Corynespora cassiicola, to impact soya bean yield, this study investigated the C. cassiicola‐induced perturbations in the photosynthesis of soya bean plants from cultivars Fundacep 59 (moderately resistant) and TMG 132 (susceptible) by examining the chlorophyll (Chl) a fluorescence parameters and imaging and the photosynthetic pigment pools. The area under disease progress curve decreased by 38% for plants from cultivar Fundacep 59 in comparison with plants from cultivar TMG 132. The concentration of total Chla+b significantly increased by 16% and the Chla+b/carotenoids ratio significantly decreased by 11% for plants from cultivar Fundacep 59 in comparison with plants from cultivar TMG 132. Significant decreases of 31% and 8%, respectively, for the concentration of Chla+b and the Chla+b/carotenoids ratio occurred for inoculated plants in comparison with noninoculated ones regardless of the cultivar. As target spot developed, the values of maximal photosystem II quantum yield (Fv/Fm), effective photosystem II quantum yield [Y(II)], quantum yield of regulated energy dissipation [Y(NPQ)] and quantum yield of nonregulated energy dissipation [Y(NO)] increased, especially for plants from cultivar TMG 132. There were positive correlations of area under disease progress curve (AUDPC) with both Y(NPQ) and Y(NO) regardless of the cultivar. For cultivar TMG 132, the correlation between AUDPC and the electron transport rate was negative. Based on the analysis of the Chl a fluorescence, it was possible to elucidate the enormous potential of target spot to impair the functionality on the photosynthetic apparatus that may help the plants to invest in metabolic pathways involved in host defence responses.
Effects of forage source and particle size on feed sorting, milk production and nutrient digestibility in lactating dairy cows
Authors: Jiang Fugui , Lin Xueyan , Yan Zhengui , Hu Zhiyong , Wang Yun , Wang Zhonghua
Published: September 2018

The objectives of this study were to determine the effects of forage source (quality) and particle size on feed sorting, milk production and nutrient digestibility in lactating dairy cows. Twelve multiparous lactating Holstein cows were used in a replicated 4 × 4 Latin square experiment with a 2 × 2 factorial arrangement of treatments. Treatments were as follows: (a) feeding long oaten hay (OL), (b) feeding short oaten hay (OS), (c) feeding long wild‐rye hay (WL) and (d) feeding short wild‐rye hay (WS). The sorting activity of cows fed wild‐rye hay diets was greater than that of cows fed oaten hay diets. Sorting activity decreased with reduced forage particle size (FPS) for wild‐rye hay diets but was not affected for oaten hay diets. Cows fed oaten hay diets had a similar dry matter intake (DMI), but higher total tract nutrient digestibility, and hence higher milk yield than cows fed wild‐rye hay diets. The increase in DMI as a result of reduced FPS was significant in cows fed wild‐rye hay diets. Feed efficiency (4% fat‐corrected milk (FCM)/DMI) decreased from 1.18 to 1.11 when FPS decreased, but was not affected by the forage source. The digestibility of DM, crude protein (CP) and organic matter (OM) in the total tract was decreased by a reduction in FPS for wild‐rye hay diets, but was not affected for oaten hay diets. In conclusion, cows fed high‐quality forage (oaten hay) had a lower sorting activity and higher production performance than those fed poor‐quality forage (wild‐rye hay). The optimal dietary FPS in lactating dairy cows should take the effect of forage source into account.
On the Sensitivity of Granger Causality to Errors‐In‐Variables, Linear Transformations and Subsampling
Authors: Anderson Brian D.O. , Deistler Manfred , Dufour Jean‐Marie
Published: September 2018

This article studies the sensitivity of Granger causality to the addition of noise, the introduction of subsampling, and the application of causal invertible filters to weakly stationary processes. Using canonical spectral factors and Wold decompositions, we give general conditions under which additive noise or filtering distorts Granger‐causal properties by inducing (spurious) Granger causality, as well as conditions under which it does not. For the errors‐in‐variables case, we give a continuity result, which implies that: a ‘small’ noise‐to‐signal ratio entails ‘small’ distortions in Granger causality. On filtering, we give general necessary and sufficient conditions under which ‘spurious’ causal relations between (vector) time series are not induced by linear transformations of the variables involved. This also yields transformations (or filters) which can eliminate Granger causality from one vector to another one. In a number of cases, we clarify results in the existing literature, with a number of calculations streamlining some existing approaches.
Outcomes after placement of a SX‐ELLA oesophageal stent for refractory variceal bleeding—A national multicentre study
Authors: Pfisterer Nikolaus , Riedl Florian , Pachofszky Thomas , Gschwantler Michael , König Kurt , Schuster Benjamin , Mandorfer Mattias , Gessl Irina , Illiasch Constanze , Fuchs Eva‐Maria , Unger Lukas , Dolak Werner , Maieron Andreas , Kramer Ludwig , Madl Christian , Trauner Michael , Reiberger Thomas
Published: September 2018

Background

Current guidelines favour the use of bleeding stents over balloon tamponade (BT) for refractory variceal bleeding (VB) from oesophageal varices. However, data on the efficacy and safety of self‐expandable metal SX‐ELLA Danis stents (SEMS) are limited.

Methods

Cirrhotic patients receiving SEMS for VB at four tertiary care centres were included in this retrospective multicentre study. Rates of failure‐to‐control bleeding (within 5 days) and bleeding‐related mortality (6 weeks) were assessed.

Results

SEMS controlled VB in 79.4% (27/34) of patients. In the rest of patients, other rescue treatments including endoscopic band ligation (EBL, n = 3), SEMS renewed (n = 2) or Linton (n = 2) were applied; however, VB was only controlled in one patient. Early rebleeding within six weeks occurred in 17.6% (6/34) patients. Median SEMS dwell time was three (IQR:6) days. Overall n = 13/34 (38.2%) patients died with SEMS in situ. After SEMS removal, rebleeding and bleeding‐related death occurred in n = 7 (35%) and n = 5 (14.7%) patients respectively. Only 32.4% (10/34) patients did not experience any rebleeding within six weeks after SEMS removal. Bleeding‐related mortality was 47.1% (n = 16/34) and the median survival after SEMS placement was 2.1 months. Notably, no patient received an early transjugular intrahepatic portosystemic shunt (TIPS). The most common adverse events were stent dislocations (n = 13; 38.2%), while ulcers/necrosis of the oesophageal mucosa was seen in only four (11.8%) patients.

Conclusion

SEMS controlled refractory VB in most patients. However, bleeding‐related mortality remained high. While SEMS dislocations were frequent, ulcers/necrosis of the oesophagus was rare. Further studies should investigate whether the wider use of early TIPS reduces bleeding‐related mortality after SEMS placement.
Hepatic fat as clinical outcome and therapeutic target for nonalcoholic fatty liver disease
Authors: Pelusi Serena , Valenti Luca
Published: September 2018

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of advanced liver disease in Western countries. NAFLD is defined in the presence of increased hepatic fat content, which is mainly stored under the form of neutral lipids within intracellular droplets and is not explained by at risk alcohol intake. In order to understand the pathogenesis, monitor the progression and find novel treatments for this condition, previous research efforts mainly addressed the role of inflammation. However, very recent data seem to suggest that hepatic lipid accumulation may be involved in NAFLD pathogenesis by driving secondary inflammation and fibrosis progression. Here, we will briefly review the novel results derived from natural history, genetics, imaging studies and therapeutic trials that support the notion that hepatic fat accumulation may represent a major clinical outcome and therapeutic target for NAFLD. Indeed, prospective and genetic data are consistent with hepatic fat being a driver of NAFLD progression. Furthermore, new technologies will render possible to monitor hepatic fat content without the need of invasive assessment, thereby allowing to identify patients at higher risk, and to monitor the response to drugs that act by decreasing hepatic lipid accumulation.
Stress–strain analysis of duodenal contractility in response to flow and ramp distension in rabbits fed low‐fiber diet
Authors: Liu Yue , Zhao Jingbo , Liao Donghua , Wang Guixue , Gregersen Hans
Published: September 2018

Background

Previously we demonstrated that low‐fiber diet in rabbits affects the passive mechanomorphological properties in the small intestine, resulting in reduced intestinal wall thickness and collagen content, as well as intestinal wall softening. The aim of the present study was to evaluate the contractility in rabbits on long‐term low‐fiber diet and specifically to compare the contraction threshold, the frequency, and the amplitude of flow‐induced and distension‐induced contractions in the duodenum between rabbits on normal diet and on long‐term low‐fiber diet.

Methods

Ten rabbits were fed a low‐fiber diet for 5 months (Intervention group), and five rabbits were fed normal diet (Control group). The duodenal segments were used for determination of mechanical parameters for analyses of contractility. The duodenal experiments were carried out in organ baths containing physiological Krebs solution. Pressure and diameter changes induced by contractions in response to flow and ramp distension were measured. The frequencies and amplitude of contractions were analyzed. Distension‐induced contraction thresholds and maximum contraction amplitude of flow‐induced contractions were calculated in terms of mechanical stress and strain. Multiple linear regression analyses were applied to study dependencies between contractility parameters and wall thickness, wall area, and muscle layer thickness.

Key results

During distension, the pressure, stress, and strain thresholds for induction of phasic contraction were biggest in the Intervention Group (P < 0.05). In addition, the contraction frequencies during flow‐induced contraction were highest in the Intervention Group (P < 0.05), whereas the maximum contraction amplitudes in terms of pressure, diameter, stress, and strain were lowest in the Intervention Group (P < 0.05). The contraction thresholds and contraction frequencies were negatively associated with the wall thickness, wall area, and muscle layer thickness, whereas maximum contraction amplitudes were positively associated with the wall thickness, wall area, and muscle layer thickness.

Conclusions and inferences

Duodenal contractility in rabbits fed with long‐term low‐fiber diet exhibited low contraction amplitudes and high contraction thresholds and frequencies. The changes were associated with the low‐fiber diet‐induced histomorphological remodeling. Studies on detailed structural and functional diet‐induced changes in smooth muscle and intestinal nerves are needed for better understanding the remodeling mechanisms.
Patients diagnosed with long QT syndrome after repair of congenital heart disease
Authors: Song Mi Kyoung , Bae Eun Jung , Kim Gi Beom , An Hyo Soon , Ahn Kyung Jin , Seong Moon‐Woo , Park Sung Sup
Published: September 2018

Background

Patients with repaired congenital heart disease (CHD) can have both depolarization and repolarization abnormalities. A coexisting long QT syndrome (LQTS) may cause electrical instability in these patients; however, diagnosing LQTS is difficult owing to intraventricular conduction delay or paced rhythm after the operation. We report on six patients diagnosed with LQTS after CHD repair.

Methods

We investigated two male and four female patients. Clinical data, electrocardiographic findings, and genetic analysis results were reviewed.

Results

The range of patient age at LQTS diagnosis was 1.4‐22 years. There were two patients with tetralogy of Fallot, four with septal defect, and one with tricuspid atresia. All patients underwent total correction or a staged operation, without events. The diagnosis of LQTS was made in four asymptomatic patients and two symptomatic patients with recurrent syncope and ventricular fibrillation. During the postoperative follow‐up, their median QTc interval and QTc dispersion increased (from 474 and 41 ms preoperatively to 541 and 141 ms postoperatively, respectively; P = 0.043). T‐wave notching over three leads was observed in three patients. Genetic analysis showed SCN5A mutation in one, KCNH2 mutation in three, KCNQ1 mutation in one, and no identified mutation in one patient. An implantable cardioverter defibrillator was placed in two patients.

Conclusion

A coexisting LQTS may confer additional risk for arrhythmia and sudden cardiac death in patients with CHD. Suspicion of LQTS and careful monitoring of the QT interval and T‐wave morphology are important during the follow‐up of patients with repaired CHD.
Necrotizing fasciitis caused by Mucor indicus in a pediatric bone marrow transplant recipient
Authors: Bloch Deborah , Gonzalez Mark D. , Haight Ann , Abramowsky Carlos , Yildirim Inci
Published: September 2018

Necrotizing fasciitis is a life‐threatening, rapidly progressing infection of fascia and subcutaneous cellular tissue typically caused by mixed aerobic and anaerobic bacteria. We present a case report of an immunocompromised 4‐year‐old female with necrotizing fasciitis from a rare fungal organism, Mucor indicus. The patient underwent multiple debridements and was treated for 10 months, first on liposomal amphotericin B (2 months) then posaconazole (8 months). Mucor indicus is a rarely described pathogen with only nine other cases described. Identification of this organism remains a challenge, and the need for further understanding of risk factors and organism susceptibility testing to help guide treatment is crucial.
Protective Effect of Baicalin Against TLR4‐mediated UVA‐induced Skin Inflammation
Authors: Sherwani Mohammad Asif , Yang Kevin , Jani Aditi , Abed Reham A. , Taufique Abdul Karim , Dosunmu Tolulope Gid , Yusuf Nabiha
Published: September 2018

UVA irradiation is known to cause photoaging via production of reactive oxygen species (ROS) and activation of inflammatory processes. Previously, we have demonstrated that baicalin, a plant‐derived flavonoid possessing both antioxidant and anti‐inflammatory activity, protects mouse keratinocytes against damage from UVB irradiation. However, the role of baicalin in vivo has not been well studied, particularly in the setting of UVA irradiation. To explore the protective effects and mechanisms of baicalin treatment in mice after UVA irradiation, mice were exposed to acute and chronic doses of UVA irradiation with or without baicalin or vehicle. Skin samples were collected for histological staining, RNA isolation, flow cytometry and protein extraction. Our results demonstrate the protective effect of baicalin against UVA‐induced oxidative damage and inflammation in mouse skin. These effects are likely mediated via the TLR4 pathway, which may serve as a target for photochemoprevention against skin inflammation.
Gliosarcoma arising from oligodendroglioma (Oligosarcoma): A case report with genetic analyses
Authors: Tanaka Shunya , Hitotsumatsu Tsutomu , Sugita Yasuo , Ishido Katsuya , Ito Osamu , Hatae Ryusuke , Akagi Yojiro , Yoshimoto Koji , Iihara Koji
Published: September 2018

Gliosarcomas are a type of bimorphic tumor composed of glial and sarcomatous elements, and are considered to be a variant of glioblastoma, WHO grade IV. To date, only rare cases of gliosarcoma with oligodendroglial components (oligosarcoma) have been reported. We report a case of oligosarcoma consisting of gliosarcoma arising from recurrent oligodendroglioma. A 53‐year‐old man, who had undergone a gross total resection of oligodendroglioma (WHO grade II) 11 years earlier, presented with a local tumor recurrence. The patient underwent a second gross total resection, whereupon a histopathological examination further revealed residual features of classical oligodendroglioma, and newly‐developed sarcomatous characteristics. Both the primary and recurrent tumors showed 1p/19q co‐deletion and mutation of the isocitrate dehydrogenase 1 (IDH1) gene, consistent with being oligodendroglial in nature. Loss of heterozygosity (LOH) of chromosome 1p/19q and IDH1 mutation have seldom been analyzed in previous reports of oligosarcomas. We report a rare case study supported by the results of genetic analyses. Our analyses have revealed that the sarcomatous component represents a metaplastic change occurring in the oligodendroglial element.
Gene and protein expression in the reproductive tract of Brazilian Somalis rams
Authors: Bezerra Maria Júlia B. , Silva Mariana B. , Lobo Carlos H. , Vasconcelos Fábio R. , Lobo Marina D. , Monteiro‐Moreira Ana Cristina O. , Moreira Renato A. , Machado‐Neves Mariana , Figueiredo José R. , Moura Arlindo A.
Published: September 2018

Contents

Brazilian Somalis is a locally‐adapted breed of rams raised in tropical climate and native pastures. The present study was conducted to evaluate gene expression and proteome of the reproductive tract of such rams. Samples were collected from testes, epididymides, seminal vesicles and bulbourethral glands of four rams. Expression of clusterin (CLU), osteopontin (OPN) and prostaglandin D2 synthase (PGDS) genes were evaluated in all samples by real‐time PCR. Shotgun proteomic analysis was performed using samples from the head, corpus and cauda epididymides and from all other structures as well. Gene ontology terms and protein interactions were obtained from UniProtKB databases and MetaCore v.6.8 platform. CLU trasncripts were detected in the testes, epididymides, seminal vesicles and bulbourethral glands of the Somalis rams. The initial region and body of the epididymis had the greatest CLU expression. OPN mRNA was localized in all tissues of the ram reproductive tract. PGDS mRNA was detected in the testes and epididymides. Lable‐free mass spectrometry allowed the identification of 137 proteins in all samples. Proteins of the epididymis head mainly participate in cellular processes and response to stimulus, participating in catalityc activity and binding. Proteins of epididymis body acted as regulatory proteins and in cellular processes, with binding and catalytic activity. Cauda epididymis molecules were associated with cellular processes and regulation, with binding function and catalytic activity as well. Testis proteins were mainly linked to cell processes and response to stimuli, and had catalytic function. Seminal vesicle proteins were involved in regulation and mainly with binding functions. Most bulbourethral gland proteins participated in cellular processes. The present study is the first to evaluate the proteome and gene expressions in the reproductive tract of Brazilian Somalis rams. Such pieces of information bring significant cointribution for the understanding of the reproductive physiology of locally‐adapted livestock.
The heritability of pampiniform plexus vessel size and varicocoele in boars
Authors: Gruhot Tasha R. , Rempel Lea A. , Spangler Matthew L. , Kachman Stephen D. , Mote Benny E.
Published: September 2018

Contents

Ultrasonography was used to capture a coronal–sagittal image of the veins of the pampiniform plexus (PP) and the testicular artery of 327 maternal‐line boars at approximately 6 months of age at the University of Nebraska—Lincoln. Varicocoele was diagnosed by two methods. Method 1 diagnosed varicocoele when the average vessel area on one side of the scrotum was 1.5 times larger than the average vessel area on the other side of the scrotum. Method 2 diagnosed varicocoele when the average vessel area on one side of the scrotum of a boar was 1.5 times larger than the average vessel on the same side of the scrotum of the boar's cohorts (same population and year). Varicocoele was diagnosed in 23.17% and 15.1% of boars measured using method 1 and method 2, respectively. Ultrasonography showed to be an effective means to measure PP vessel size in boars and may even allow for earlier detection of varicocoele than by using palpation. Animal models were employed to estimate the heritability for: average area of right PP vessels (0.52), average area of the left PP vessels (0.46), varicocoele presence using method 1 (0.26) and varicocoele presence using method 2 (0.25). These heritability estimates suggest that vessel size and varicocoele could be selected against in breeding programmes to potentially improve boar semen quality.
Noninvasive measurements of ovarian activity in Beira antelope (Dorcatragus megalotis)
Authors: Wolf Tanja E. , Arif Abdi , Bennett Nigel C. , Ganswindt André
Published: September 2018

Contents

As the natural habitat of more and more species becomes depleted, captive breeding programmes have become established to bring species back from the brink of extinction. Monitoring the reproductive status of an individual is essential in order to improve breeding success. Traditional methods have involved stressful blood sampling, and thus noninvasive methods have been proven to be reliable alternatives for monitoring reproductive function in both captive and free‐ranging animals. Subsequently, noninvasive methods have become an invaluable tool in longitudinal studies and conservation efforts, as animals can be observed without, or minimal human contact. The Beira antelope is a small antelope endemic to the northern part of the Horn of Africa. Population numbers of the Beira have been declining over the last few decades due to habitat fragmentation. We show here that the reproductive cycle of female Beira antelopes can be monitored noninvasively, by using faecal samples to analyse oestrogen (fEM) as well as progestagen (fPM) metabolites. The profiles of fPM and fEM of both females showed regular cyclic patterns in which the follicular and luteal phases could be distinguished. The overall mean cycle length is 22 days (range: 21–25 days), with a mean length of the follicular phase of 6 days (range: 4–7 days) and a mean length for the luteal phase being 15 days (range: 12–16 days). The suitability of these noninvasive techniques should assist in optimizing breeding efforts of this endemic small antelope in captivity. Being noninvasive, this method could also be a useful tool for monitoring reproductive function in the dwindling wild populations.
The Jazziness of Local Food Practice Work: Organization‐Level Ingenuity and the Entrepreneurial Formation and Evolution of Local Food Systems
Authors: Mars Matthew M. , Schau Hope Jensen
Published: September 2018

Local food systems (LFSs) are complex and diverse social structures. The processes that influence the formation and evolution of LFSs are obscure, relatively uncoordinated, and somewhat mysterious. This study develops a stronger understanding of such processes through a qualitative exploration of the influence of routine practice work at the organization level on the entrepreneurial development of two distinct LFSs in the Southwest region of the United States: southeastern Arizona and Albuquerque−Santa Fe. We gathered data between August 2014 and September 2017 through semistructured interviews with and direct observations of 53 local food practitioners operating in one of the two LFSs. Theoretical principles of institutional entrepreneurship, embedded agency, and practice work guided the study. The findings reveal three forms of ingenuity (technological, organizational, policy) that regularly emerge through the day‐to‐day organization‐level work of local food practitioners. We argue that the system‐level influence of these forms, whether intentional or not, are indicators of the embedded agency of the practitioners and their capacities to serve as institutional entrepreneurs. We discuss implications for both practice and future research.
“I Don’t Want to Work in Agriculture!” The Transition from Agricultural Education to the Labor Market in Rural Russia
Authors: Unay‐Gailhard İlkay , Bavorová Miroslava , Bednaříková Zuzana , Ponkina Elena V.
Published: September 2018

In Russia, the shift in career incentives from agriculture‐related jobs to other sectors, even among agriculturally educated students, presents two main challenges to rural labor markets. The first relates to the shortage of agricultural employees. The second concerns difficulties in the school‐to‐work transition, characterized by long periods of unemployment. This article addresses these challenges by studying the career incentives of postsecondary agriculturally educated students, based on data from the Altai region, Siberia (N = 474). We use a logit regression to predict the probability of career transition, given the incentives. We examine whether familial background and life expectations are associated with plans to pursue a career in agriculture within a life course context. The results show that students’ career plans with respect to agriculture vary according to both sociofamilial background and views about one’s life course.
Leonard Lawlor’s Renewal of Thinking
Authors: Haddad Samir
Published: September 2018

In this paper I analyze Leonard Lawlor’s strategy of inheriting from the tradition, highlighting the way he traces and amplifies a series of conceptual transformations that take place across twentieth‐century continental philosophy. Focusing on the particular movement from metaphysics to ethics enacted in From Violence to Speaking Out, I raise three concerns regarding Lawlor’s ethics of “the least violence,” arguing that there is a problem with a quantitative understanding of this notion, that the quality of potentiality attributed to it needs more clarification, and that Lawlor’s proposal of a radical letting be has more dangers than he seems to realize.
Violence and Reactions
Authors: Lawlor Leonard
Published: September 2018

This article has two parts. On the one hand, it summarizes a lot of the work I have done over the last 10 years. The summary starts with three phenomenological insights: into temporalization, into intersubjectivity, and into foundations. It ends with a discussion of ethics based on Kant and Bergson. On the other hand, the article presents my responses to three commentators on my work: Emilia Angelova, Edward S. Casey, and Samir Haddad. All three raise important questions about my work. All three bring me back to the main point of my work: strategies for letting others be free. Thus, to use a phrase that probably seems out of date, this article could have been called “strategies of deconstruction.”