bluuebunny/crossref_metadata_2025 huggingface dataset:
Supra-ilioinguinal versus modified Stoppa approach in the treatment of acetabular fractures: reduction quality and early clinical results of a retrospective study
Authors: Yao Sheng , Chen Kaifang , Ji Yanhui , Zhu Fengzhao , Zeng Lian , Xiong Zekang , Sun Tingfang , Yang Fan , Liu Jia , Guo Xiaodong
Published: November 2019

Background

To compare the efficacy of the operative techniques, complications, reduction quality and hip functional recovery by using the supra-ilioinguinal approach and the modified Stoppa approach for the management of acetabular fractures.

Methods

A consecutive cohort of 60 patients from September 2014 to October 2017 with displaced acetabular fractures involving the quadrilateral plate were treated operatively with supra-ilioinguinal approach (group A) and modified Stoppa approach (group B), respectively. There were 36 patients in group A and 24 patients in group B. The surgical details, complications, radiographic and clinical results were recorded. The quality of reduction was assessed by measuring the residual step and gap displacement of postoperative CT with a standardized digital method.

Results

The complications, reduction quality (gaps and steps) and hip function recovery had no significant statistical difference in approaches. The mean operative time was shorter and the mean intraoperative haemorrhage was less in group A. There were statistical differences in the operative time (P = 0.025) and intraoperative haemorrhage (P = 0.003) between the supra-ilioinguinal approach and the modified Stoppa approach.

Conclusion

Compared to the modified Stoppa approach, the supra-ilioinguinal approach provides a closer visualization to the quadrilateral plate, the operative time was shorter and the intraoperative haemorrhage was clearly less. It is at least equal to or could be a better choice to deal with complicated acetabular fractures especially involving the quadrilateral plate and the anterior one third of the iliac bone.
Comparison of modified MAZE with minimally invasive monopolar ablation and traditional bipolar radiofrequency ablation in the treatment of atrial fibrillation
Authors: Si Wei , Yang Sijia , Pan Linhui , Li Chengchegn , Ma Liang
Published: November 2019

Background and aim of the study

Atrial fibrillation (AF) is the most common atrial arrhythmia. Our aim was to compare the outcomes of atrial fibrillation treatment with original modified minimally invasive MAZE using monopolar radiofrequency ablation (mi-MAZE) and open surgery MAZE using bipolar radiofrequency ablation (os-MAZE).

Methods

We searched the associated patients’ information on the medical record system of the First Affiliated Hospital, School of Medicine, Zhejiang University. Statistical Package for Social Sciences (SPSS) was used to analyse the data. The primary outcome is the atrial fibrillation ablation rate 3 months, 6 months, 12 months after operation. And secondary outcome is the postoperative quality of life.

Results

The mi-MAZE group included 42 patients and the os-MAZE group had 65 patients. Three months after surgery, we found that 31 patients (77.5%) in the mi-MAZE group were sinus rhythm and 44 (71.0%) recovered sinus rhythm in the os-MAZE group. We followed up these patients on the phone or in person and scored them on the SF-36 scale. The results were found to be 120.2 ± 8.10 vs 110.6 ± 6.58 (mi-MAZE vs os-MAZE, P < 0.001).

Conclusions

There was no significant difference of atrial fibrillation ablation rate (sinus rhythm recovery rate) between the mi-MAZE group and the os-MAZE group. The postoperative quality of life in mi-MAZE group was higher than that in os-MAZE group.
Description of two Serratia marcescens associated mastitis outbreaks in Finnish dairy farms and a review of literature
Authors: Friman Mari Johanna , Eklund Marjut Hannele , Pitkälä Anna Helena , Rajala-Schultz Päivi Johanna , Rantala Merja Hilma Johanna
Published: November 2019

Background

Infection withSerratiaspp. have been associated with mastitis outbreaks in dairy cattle herds. Environmental contamination or a point source, like a teat dip product, have often been observed to be potential sources of such outbreaks. We describe twoSerratia marcescensassociated mastitis outbreaks associated with a contaminated teat dip containing a tertiary alkyl amine,n,n-bis (3-aminopropyl) dodecylamine in two dairy cattle farms in Finland.S. marcescensstrains isolated from milk and environmental samples were identified by the MALDI-TOF method.

Results

Six specimens (n = 19) on Herd 1 and all specimens (n = 9) on Herd 2 were positive forS. marcescens. Positive specimens were from mastitis milk and teat dip liquid and equipment. Bacteria were not isolated from the unopened teat dip canister. The same clone ofS. marcescenswas isolated from milk samples and teat dip samples within the farms. Pulsed field gel electrophoresis results to theS. marcescensisolates from these two different herds were tested with unweighted pair-group method using arithmetic average clustering analysis. The isolates were not same clone in both herds, because similarity in that test was only 75% when cut-off value to similarity is 85%.

Conclusions

Our investigation showed that the post milking teat dip and/or temporary containers were contaminated withS. marcescensand these were most likely the sources for new mastitis cases. The negative result from the unopened teat dip canister and positive results from refillable containers demonstrated that the product itself was not contaminated withS. marcescensat the production unit, but became contaminated at the farm level.
Identifying climate-sensitive infectious diseases in animals and humans in Northern regions
Authors: Omazic Anna , Bylund Helena , Boqvist Sofia , Högberg Ann , Björkman Christer , Tryland Morten , Evengård Birgitta , Koch Anders , Berggren Camilla , Malogolovkin Alexander , Kolbasov Denis , Pavelko Nataly , Thierfelder Tomas , Albihn Ann
Published: November 2019

Background

General knowledge on climate change effects and adaptation strategies has increased significantly in recent years. However, there is still a substantial information gap regarding the influence of climate change on infectious diseases and how these diseases should be identified. From a One Health perspective, zoonotic infections are of particular concern. The climate in Northern regions is changing faster than the global average. This study sought to identify climate-sensitive infectious diseases (CSIs) of relevance for humans and/or animals living in Northern regions. Inclusion criteria for CSIs were constructed using expert assessments. Based on these principles, 37 potential CSIs relevant for Northern regions were identified. A systematic literature search was performed in three databases using an explicit stepwise approach to determine whether the literature supports selection of these 37 potential CSIs.

Results

In total, 1275 nominated abstracts were read and categorised using predefined criteria. Results showed that arthropod vector-borne diseases in particular are recognised as having potential to expand their distribution towards Northern latitudes and that tick-borne encephalitis and borreliosis, midge-borne bluetongue and the parasitic infection fasciolosis can be classified as climate-sensitive. Many of the other potential CSIs considered are affected by extreme weather events, but could not be clearly classified as climate-sensitive. An additional literature search comparing awareness of climate influences on potential CSIs between 1997–2006 and 2007–2016 showed an increase in the number of papers mentioning effects of climate change.

Conclusions

The four CSIs identified in this study could be targeted in a systematic surveillance programme in Northern regions. It is evident that climate change can affect the epidemiology and geographical range of many infectious diseases, but there were difficulties in identifying additional CSIs, most likely because other factors may be of equal or greater importance. However, climate-ecological dynamics are constantly under change, and therefore diseases may fall in or out of the climate-sensitive definition over time. There is increasing awareness in the literature of the effects of climate change on infectious diseases over time.
Association between DLA-DRB1.2 allelic diversity and development of mammary gland tumors in dogs
Authors: Vahedi Seyed Milad , Nikbakht Gholamreza , Jamshidi Shahram , Lankarani Leila , Alimi Nika , Esmailnejad Atefeh
Published: November 2019

Background

The major histocompatibility complex (MHC) is the best-characterized genetic region related to resistance/susceptibility to a wide range of infectious and immune-mediated diseases. Evidences suggest that MHC class II genes may play an important role in developing different types of tumors including breast cancer. Canine mammary gland tumors (CMTs) are the most common neoplasms in female dogs. In the current study, the association of canine MHC class II DLA-DRB1.2 genotypes with development of mammary gland tumor profiles in dogs was investigated. DLA-DRB1.2 allelic diversity was determined in 40 dogs (18 CMT cases and 22 controls) using HRM technique and DNA sequencing. Association of the DLA-DRB1.2 genotypes with CMT profiles was expressed as odds ratio (OR).

Results

Based on the histopathological typing of tumors, CMT cases were categorized into 4 groups: simple carcinoma, complex carcinoma, carcinoma arising in a benign tumor and special types of carcinoma. A total of eight HRM profiles (A to H) were identified in dogs sampled. The association study revealed a significant correlation between DLA-DRB1.2 genotypes with different CMT profiles. The E genotype was significantly associated with increased risk of carcinoma arising in a benign tumor, and the B genotype represented a positive correlation with complex carcinoma. Significant association was also observed between the heterozygosity of DLA-DRB1.2 genotypes and decreased risk of developing tumor in dogs.

Conclusions

These results provide additional support for the association between DLA-DRB1 genes and development of mammary gland tumors in dogs and could potentially be used for early diagnosis of neoplasia and identifying susceptible dogs.
Antigen-labeled mesoporous silica-coated Au-core Pt-shell nanostructure: a novel nanoprobe for highly efficient virus diagnosis
Authors: Li Aiyun , Long Lin , Liu Fengshou , Liu Jianbo , Wu Xiaochun , Ji Yinglu
Published: November 2019

Background

As an emerging research area of artificial enzymes, nanozyme, the catalytic nanomaterials with enzyme-like characteristics, have attracted enormous attention in research. Here, a nanozyme probe has been realized by utilizing antigen-labeled mesoporous silica-encapsulated Au-core Pt-shell (Au@Pt@SiO2) nanostructures for the diagnosis of rubella virus (RV). Pt nanoparticles have been suggested to act as potent peroxidase mimetics with high activities. However, smaller Pt nanoparticles are very easily aggregated, which has negative effects on the catalytic activities.

Results

In this work, the use of gold nanorod as the support favours the well dispersion of the small Pt nanoparticles to improve the stability of them. Furthermore, the designed the silica shell could also isolate the recognition antigens from the surface reactive sites, retaining catalytic activity of the inner nanozyme. In addition, compared with antigen-labeled horseradish peroxidase (HRP), the antigen-labeled Au@Pt@SiO2 nanozyme was more stable and robust. A capture enzyme-linked immunosorbent assay (ELISA) for the determination of RV showed that the antigen-labeled Au@Pt@SiO2 nanozyme-based ELISA exhibited good sensitivity.

Conclusions

The highly sensitive peroxidase-like activity of antigen-labeled Au@Pt@SiO2 nanozyme, along with their catalytic stability and robustness, can facilitate their utilization in biochemical assays and clinical diagnosis.
Prevention of lymphedema via axillary reverse mapping for arm lymph-node preservation following breast cancer surgery: a randomized controlled trial
Authors: Faisal Mohammed , Sayed Mohamed Gamal , Antonious Kerolos , Abo Bakr Ahmmed , Farag Sherif Hussein
Published: November 2019

Background

Breast cancer, with an incidence of 32%, is the most frequent cancer among Egyptian women. The frequency of arm lymphedema after axillary surgery for breast cancer ranges from 7 to 77%. Axillary reverse mapping is a technique aimed to distinguish and conserve upper-limb lymphatics and lymph nodes during the course of axillary surgery and could help to prevent arm lymphedema.

Methods

Patients (n = 48) were prepared for axillary lymph-node dissection. The study group and the control group each contained 24 individuals. In the study group, following dye injection, stained arm lymph nodes and lymphatics were conserved during axillary dissection, whereas control-group participants underwent the conventional procedure. All participants were re-evaluated after 6 months, and the incidence of lymphedema was recorded by measuring arm circumference at a level 10 cm proximal to the medial epicondyle. Arm lymphedema was defined as a change in the circumference of the ipsilateral upper extremity > 2 cm during the follow-up period.

Results

Age, tumor size and N stage were not significantly different between the study and control groups. Lymph-node visualization was achieved in 20 participants (83.3%) in the study group. Suspicious stained lymph nodes were surgically removed from four individuals but showed no metastatic involvement. In 20 individuals in the study group, no stained lymph nodes were removed. The incidence of lymphedema in the control group was 16.7%, and the incidence in the study group was 4.2%.

Conclusions

Axillary reverse mapping is a minimally invasive technique that can be performed during axillary lymph-node dissection, helping to prevent the subsequent development of arm lymphedema.

Trial registration

#SCURCTN3276, retrospectively registered on 11 April 2017 at Research Ethics Committee at the Faculty of medicine-Suez Canal University.
CRISPR/Cas9-mediated knockout of NSD1 suppresses the hepatocellular carcinoma development via the NSD1/H3/Wnt10b signaling pathway
Authors: Zhang Shuhua , Zhang Fan , Chen Qing , Wan Chidan , Xiong Jun , Xu Jianqun
Published: November 2019

Background

The NSD family of histone lysine methyltransferases have emerged as important biomarkers that participate in a variety of malignancies. Recent evidence has indicated that somatic dysregulation of the nuclear receptor binding SET domain-containing protein 1 (NSD1) is associated with the tumorigenesis in HCC, suggesting that NSD1 may serve as a prognostic target for this malignant tumor. However, its mechanism in human hepatocellular carcinoma (HCC), the major primary malignant tumor in the human liver, remains unclear. Hence, we investigated how NSD1 regulated HCC progression via regulation of the Wnt/β-catenin signaling pathway.

Methods

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis was performed to identify the expression of NSD1 in HCC cells and clinically obtained tissues. The relationship between NSD1 expression and prognosis was analyzed by Kaplan-Meier survival curve. Further, a NSD1 knockout cell line was constructed by CRISPR/Cas9 genomic editing system, which was investigated in a battery of assays such as HCC cell proliferation, migration and invasion, followed by the investigation into NSD1 regulation on histone H3, Wnt10b and Wnt/β-catenin signaling pathway via ChIP. Finally, a nude mouse xenograft model was conducted in order to assess tumorigenesis affected by NSD1 knockout in vivo.

Results

NSD1 was overexpressed in HCC tissues and cell lines in association with poor prognosis. Knockout of NSD1 inhibited the proliferation, migration and invasion abilities of HCC cells. CRISPR/Cas9-mediated knockout of NSD1 promoted methylation of H3K27me3 and reduced methylation of H3K36me2, which inhibited Wnt10b expression. The results thereby indicated an inactivation of the Wnt/β-catenin signaling pathway suppressed cell proliferation, migration and invasion in HCC. Moreover, these in vitro findings were reproduced in vivo on tumor xenograft in nude mice.

Conclusion

In conclusion, the study provides evidence that CRISPR/Cas9-mediated NSD1 knockout suppresses HCC cell proliferation and migration via the NSD1/H3/Wnt10b signaling pathway, suggesting that NSD1, H3 and Wnt10b may serve as potential targets for HCC.
Physiological mechanism of improved tolerance of Saccharomyces cerevisiae to lignin-derived phenolic acids in lignocellulosic ethanol fermentation by short-term adaptation
Authors: Gu Hanqi , Zhu Yuyong , Peng Yanfang , Liang Xiujun , Liu Xiaoguang , Shao Lingzhi , Xu Yanyan , Xu Zhaohe , Liu Ran , Li Jie
Published: November 2019

Background

Phenolic acids are lignin-derived fermentation inhibitors formed during many pretreatment processes of lignocellulosic biomass. In this study, vanillic,p-hydroxybenzoic, and syringic acids were selected as the model compounds of phenolic acids, and the effect of short-term adaptation strategies on the tolerance ofS. cerevisiaeto phenolic acids was investigated. The mechanism of phenolic acids tolerance in the adapted yeast strains was studied at the morphological and physiological levels.

Results

The multiple phenolic acids exerted the synergistic inhibitory effect on the yeast cell growth. In particular, a significant interaction between vanillic and hydroxybenzoic acids was found. The optimal short-term adaptation strategies could efficiently improve the growth and fermentation performance of the yeast strain not only in the synthetic media with phenolic acids, but also in the simultaneous saccharification and ethanol fermentation of corncob residue. Morphological analysis showed that phenolic acids caused the parental strain to generate many cytoplasmic membrane invaginations with crack at the top of these sites and some mitochondria gathered around. The adapted strain presented the thicker cell wall and membrane and smaller cell size than those of the parental strain. In particular, the cytoplasmic membrane generated many little protrusions with regular shape. The cytoplasmic membrane integrity was analyzed by testing the relative electrical conductivity, leakage of intracellular substance, and permeation of fluorescent probe. The results indicated that the short-term adaptation improved the membrane integrity of yeast cell.

Conclusion

The inhibition mechanism of phenolic acid might be attributed to the combined effect of the cytoplasmic membrane damage and the intracellular acidification. The short-term adaptation strategy with varied stressors levels and adaptive processes accelerated the stress response of yeast cell structure to tolerate phenolic acids. This strategy will contribute to the development of robust microbials for biofuel production from lignocellulosic biomass.
Associations between Water, Sanitation and Hygiene (WASH) and trachoma clustering at aggregate spatial scales, Amhara, Ethiopia
Authors: Altherr Forest M. , Nute Andrew W. , Zerihun Mulat , Sata Eshetu , Stewart Aisha E. P. , Gessese Demelash , Melak Berhanu , Astale Tigist , Ayenew Gedefaw , Callahan E. Kelly , Chanyalew Melsew , Gashaw Bizuayehu , Waller Lance A. , Tadesse Zerihun , Nash Scott D.
Published: November 2019

Background

Trachoma is the leading infectious cause of blindness globally. The WHO has recommended the SAFE (Surgery, Antibiotics, Facial cleanliness and Environmental improvements) strategy to eliminate trachoma as a public health problem. The F and E arms of the strategy will likely be important for sustained disease reductions, yet more evidence is needed detailing relationships between hygiene, sanitation and trachoma in areas with differing endemicity. This study addressed whether the regional differences in water, sanitation, and hygiene (WASH) variables were associated with the spatial distribution of trachomatous inflammation-follicular (TF) among children aged 1 to 9 years in the Amhara National Regional State of Ethiopia.

Methods

Data from 152 multi-stage cluster random trachoma surveys were used to understand the degree of clustering of trachoma on two spatial scales (district and village) in Amhara using a geographical information system and the Getis-Ord Gi* (d) statistic for local clustering. Trained and certified graders examined children for the clinical signs of trachoma using the WHO simplified system. Socio-demographic, community, and geoclimatic factors thought to promote the clustering of the disease were included as covariates in a logistic regression model.

Results

The mean district prevalence of TF among children aged 1 to 9 years in Amhara was 25.1% (standard deviation = 16.2%). The spatial distribution of TF was found to exhibit global spatial dependency with neighboring evaluation units at both district and village level. Specific clusters of high TF were identified at both the district and the village scale of analysis using weighted estimates of the prevalence of the disease. Increased prevalence of children without nasal and ocular discharge as well as increased prevalence of households with access to a water source within 30 minutes were statistically significantly negatively associated with clusters of high TF prevalence.

Conclusions

Water access and facial cleanliness were important factors in the clustering of trachoma within this hyperendemic region. Intensified promotion of structural and behavioral interventions to increase WASH coverage may be necessary to eliminate trachoma as a public health problem in Amhara and perhaps other hyper-endemic settings.
A systematic review of natural killer cells profile and cytotoxic function in myalgic encephalomyelitis/chronic fatigue syndrome
Authors: Eaton-Fitch Natalie , du Preez Stanley , Cabanas Hélène , Staines Donald , Marshall-Gradisnik Sonya
Published: November 2019

Background

Compromised natural killer (NK) cell cytotoxic function is a well-documented and consistent feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Other outcomes evaluated in NK cells of ME/CFS patients, however, remain equivocal. The aim of this study was to conduct a systematic review of the literature regarding NK cell phenotype, receptor expression, cytokine production and cytotoxicity in ME/CFS patients and determine the appropriateness as a model for ME/CFS.

Methods

Medline (EBSCOHost), Scopus, EMBASE and PubMed databases were systematically searched to source relevant papers published between 1994 and March 2018. This review included studies examining NK cells’ features in ME/CFS patients compared with HC following administration of specific inclusion and exclusion criteria. Secondary outcomes included genetic analysis in isolated NK cells or quality of life assessment. Quality assessment was completed using the Downs and Black checklist in addition to The Joanna Briggs Institute checklist.

Results

Seventeen eligible publications were included in this review. All studies were observational case control studies. Of these, 11 investigated NK cell cytotoxicity, 14 investigated NK cell phenotype and receptor profiles, three examined NK cell cytokine production, six investigated NK cell lytic protein levels and four investigated NK cell degranulation. Impaired NK cell cytotoxicity remained the most consistent immunological report across all publications. Other outcomes investigated differed between studies.

Conclusion

A consistent finding among all papers included in this review was impaired NK cell cytotoxicity, suggesting that it is a reliable and appropriate cellular model for continued research in ME/CFS patients. Aberrations in NK cell lytic protein levels were also reported. Although additional research is recommended, current research provides a foundation for subsequent investigations. It is possible that NK cell abnormalities can be used to characterise a subset of ME/CFS due to the heterogeneity of both the illness itself and findings between studies investigating specific features of NK function.
Gradient diffusion antibiogram used directly on bronchial aspirates for a rapid diagnosis of ventilator-associated pneumonia
Authors: Burillo Almudena , de Egea Viviana , Onori Raffaella , Martín-Rabadán Pablo , Cercenado Emilia , Jiménez-Navarro Laura , Muñoz Patricia , Bouza Emilio
Published: November 2019

Background

In patients with suspected ventilator-associated pneumonia, a rapid etiological diagnosis is crucial as incorrect or delayed treatment in the first few hours leads to a worse prognosis and a higher mortality rate. This study examines the efficacy of a rapid antibiogram on bronchial aspirates in patients with suspected ventilator-associated pneumonia (VAP).

Methods

The direct gradient diffusion susceptibility testing method (GDM) on respiratory samples was compared with a standard broth microdilution method (BMD) after quantitative cultures in patients with suspicion of VAP. Samples were preselected by Gram staining (for good quality microbiological samples with a predominant single bacterial morphotype). The antibiotics tested were ceftazidime, ceftobiprole, ceftolozane-tazobactam, meropenem, doripenem, and tedizolid.

Results

Over a 16-month study period, 445 bronchial aspirate samples were selected from 1376 samples received at our laboratory from 672 adult patients. By direct plating on Mueller-Hinton agar, we recovered 504 (95.5%) of the 528 microorganisms identified by the standard semiquantitative method. Antimicrobial susceptibility testing by GDM was compared with the BMD method in 472 strains (216Enterobacteriaceae, 138P. aeruginosaand 118 S. aureus.) and 1652 individual microorganism-antimicrobial agent combinations. There was total agreement between both methods in 98% of combinations. The Kappa index between both techniques was excellent (over 80%). There was only one potential major error forP. aeruginosasusceptibility to ceftazidime.

Conclusions

The six GDM strips directly placed on plated bronchial aspirates obtained from patients with a suspicion of VAP provided accurate and reliable susceptibility results within 24 h.
Increased soluble amyloid-beta causes early aberrant brain network hypersynchronisation in a mature-onset mouse model of amyloidosis
Authors: Ben-Nejma Inès R. H. , Keliris Aneta J. , Daans Jasmijn , Ponsaerts Peter , Verhoye Marleen , Van der Linden Annemie , Keliris Georgios A.
Published: November 2019

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. According to the amyloid hypothesis, the accumulation and deposition of amyloid-beta (Aβ) peptides play a key role in AD. Soluble Aβ (sAβ) oligomers were shown to be involved in pathological hypersynchronisation of brain resting-state networks in different transgenic developmental-onset mouse models of amyloidosis. However, the impact of protein overexpression during brain postnatal development may cause additional phenotypes unrelated to AD. To address this concern, we investigated sAβ effects on functional resting-state networks in transgenic mature-onset amyloidosis Tet-Off APP (TG) mice. TG mice and control littermates were raised on doxycycline (DOX) diet from 3d up to 3 m of age to suppress transgenic Aβ production. Thereafter, longitudinal resting-state functional MRI was performed on a 9.4 T MR-system starting from week 0 (3 m old mice) up to 28w post DOX treatment. Ex-vivo immunohistochemistry and ELISA analysis was performed to assess the development of amyloid pathology. Functional Connectivity (FC) analysis demonstrated early abnormal hypersynchronisation in the TG mice compared to the controls at 8w post DOX treatment, particularly across regions of the default mode-like network, known to be affected in AD. Ex-vivo analyses performed at this time point confirmed a 20-fold increase in total sAβ levels preceding the apparition of Aβ plaques and inflammatory responses in the TG mice compared to the controls. On the contrary at week 28, TG mice showed an overall hypoconnectivity, coinciding with a widespread deposition of Aβ plaques in the brain. By preventing developmental influence of APP and/or sAβ during brain postnatal development, we demonstrated FC abnormalities potentially driven by sAβ neurotoxicity on resting-state neuronal networks in mature-induced TG mice. Thus, the Tet-Off APP mouse model could be a powerful tool while used as a mature-onset model to shed light into amyloidosis mechanisms in AD.
Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features – a retrospective analysis of the HIT ependymoma trial cohort
Authors: Jünger Stephanie T. , Mynarek Martin , Wohlers Inken , Dörner Evelyn , Mühlen Anja zur , Velez-Char Natalia , von Hoff Katja , Rutkowski Stefan , Warmuth-Metz Monika , Kortmann Rolf-Dieter , Timmermann Beate , Rahmann Sven , Klein-Hitpass Ludger , von Bueren Andre O. , Pietsch Torsten
Published: November 2019

Introduction

Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols.

Methods

Tumor samples of 134 patients aged 0.2–15.9 years treated between 1999 and 2010 according to HIT protocols were analyzed for histological features including mitotic activity, necrosis and vascular proliferation and genomic alterations by SNP and molecular inversion probe analysis. Survival analysis was performed by Kaplan-Meier method with log rank test and multivariate Cox regression analysis.

Results

Residual tumor after surgery, chromosome 1q gain and structural genomic alterations were identified as predictors of significantly shorter event-free (EFS) and overall survival (OS). Furthermore, specific histological features including vascular proliferation, necrosis and high mitotic activity were predictive for shorter OS. Multivariate Cox regression revealed residual tumor, chromosome 1q gain and mitotic activity as independent predictors of both EFS and OS. Using these independent predictors of outcome, we were able to build a 3-tiered risk stratification model that separates patients with standard, intermediate and high risk, and which outperforms current stratification procedures.

Conclusion

The integration of defined clinical, histological and genetic parameters led to an improved risk-stratification model for posterior fossa ependymoma of childhood. After validation in independent cohorts this model may provide the basis for risk-adapted treatment of children with ependymomas of the posterior fossa.
Creation and reference characterization of Edo period Japanese woodblock printing ink colorant samples using multimodal imaging and reflectance spectroscopy
Authors: Villafana Tana , Edwards Gwenanne
Published: November 2019

The Library of Congress Prints and Photographs Division holds a large collection of Edo period (1615–1868) nishiki-e, Japanese multicolored woodblock prints. The sensitivities of some of the traditional colorants to environmental and conservation treatment factors results in numerous preservation concerns. Characterization of colorants in these prints can help guide preservation policies, however, identification of colorants can be difficult and re-creation methodologies for reference samples have been elusive. This paper details reproducible colorant preparation methods and characterizes these samples using accessible non-invasive techniques, multimodal imaging and reflectance spectroscopy. A majority of the colorants can be identified using the two techniques as complementary methods.
Characteristics of relocated hypocenters of the 2018 M6.7 Hokkaido Eastern Iburi earthquake and its aftershocks with a three-dimensional seismic velocity structure
Authors: Kita Saeko
Published: November 2019

I relocated the hypocenters of the 2018 M6.7 Hokkaido Eastern Iburi earthquake and its surrounding area, using a three-dimensional seismic structure, the double-difference relocation method, and the JMA earthquake catalog. After relocation, the focal depth of the mainshock became 35.4 km. As previous studies show, in south-central Hokkaido, the Hidaka collision zone is formed, and anomalous deep and thickened forearc crust material is subducting at depths of less than 70 km. The mainshock and its aftershocks are located at depths of approximately 10 to 40 km within the lower crust of the anomalous deep and thickened curst near the uppermost mantle material intrusions in the northwestern edge of this Hidaka collision zone. Like the two previous large events, the aftershocks of this event incline steeply eastward and appear to be distributed in the deeper extension of the Ishikari-teichi-toen fault zone. The highly inclined fault in the present study is consistent with a fault model by a geodetic analysis with InSAR. The aftershocks at depths of 10 to 20 km are located at the western edge of the high-attenuation (low-Qp) zone. These kinds of relationships between hypocenters and materials are the same as the 1970 and 1982 events in the Hidaka collision zone. The anomalous large focal depths of these large events compared with the average depth limit of inland earthquakes in Japan could be caused by the locally lower temperature in south-central Hokkaido. This event is one of the approximately M7 large inland earthquakes that occurred repeatedly at a recurrence interval of approximately 40 years and is important in the collision process in the Hidaka collision zone.
Recapitulation-like developmental transitions of chromatin accessibility in vertebrates
Authors: Uesaka Masahiro , Kuratani Shigeru , Takeda Hiroyuki , Irie Naoki
Published: November 2019

The relationship between development and evolution has been a central theme in evolutionary developmental biology. Across the vertebrates, the most highly conserved gene expression profiles are found at mid-embryonic, organogenesis stages, whereas those at earlier and later stages are more diverged. This hourglass-like pattern of divergence does not necessarily rule out the possibility that gene expression profiles that are more evolutionarily derived appear at later stages of development; however, no molecular-level evidence of such a phenomenon has been reported. To address this issue, we compared putative gene regulatory elements among different species within a phylum. We made a genome-wide assessment of accessible chromatin regions throughout embryogenesis in three vertebrate species (mouse, chicken, and medaka) and estimated the evolutionary ages of these regions to define their evolutionary origins on the phylogenetic tree. In all the three species, we found that genomic regions tend to become accessible in an order that parallels their phylogenetic history, with evolutionarily newer gene regulations activated at later developmental stages. This tendency was restricted only after the mid-embryonic, phylotypic periods. Our results imply a phylogenetic hierarchy of putative regulatory regions, in which their activation parallels the phylogenetic order of their appearance. One evolutionary mechanism that may explain this phenomenon is that newly introduced regulatory elements are more likely to survive if activated at later stages of embryogenesis. Possible relationships between this phenomenon and the so-called recapitulation are discussed.
Letter to the Editor: The development of knights cabin cancer retreats: a community program to engage cancer survivors’ proactive health behaviors
Authors: Lesser Iris , McGowan Erin , Belanger Lisa
Published: November 2019

Purpose

Cancer survivors often lack the knowledge and skills to return to positive health behaviors following a cancer diagnosis. The use of retreats may be an ideal environment for cancer survivors to learn about health behaviours while receiving social support from other survivors.

Methods

Knights Cabin Cancer Retreats was created as a charitable organization in 2014 and is at no cost to participants or their supporters. Elements of the retreat include guided hikes, yoga, classes on nutrition, stress, mindfulness and sleep management techniques, all with a focus on the evidence based theories of behavioral change.

Results

Ten retreats have been hosted across Canada to date with 137 cancer survivors and their supporters. Survivors reported that their top learning outcomes from the retreat were physical activity/nutrition and behavioral change/habit development.

Conclusion

Knight’s Cabin Cancer retreats are unique in their programming with a format of health education that allows for emotional support and engagement with other cancer survivors in a therapeutically natural environment.
Climbing up and down the hierarchy of accountability: implications for organization design
Authors: Romme A. Georges L.
Published: November 2019

The notion of organizational hierarchy is disputed, also in view of the rise of new organizational forms claimed to have “hierarchies without bosses.” To better understand the contested nature of hierarchy, this essay provides a systemic perspective on organizational hierarchy defined as a sequence, or ladder, of accountability levels. I then argue this ladder can be used in a top-down manner (e.g., as a chain of command), but also in bottom-up ways (e.g., by employees taking charge of higher-level responsibilities). Subsequently, several propositions that may guide future work in this area are formulated, and the implications for organization design are fleshed out. Overall, the notion of hierarchy may become less contested by defining it as an accountability ladder which can be instantiated and used in highly different ways.
Access to high-cost medications for psoriatic arthritis in the National Health System in Brazil: the long path up to dispensation
Authors: da Silva Michael Ruberson Ribeiro , dos Santos Jéssica Barreto Ribeiro , Almeida Alessandra Maciel , Alvares-Teodoro Juliana , Kakehasi Adriana Maria , Acurcio Francisco de Assis
Published: November 2019

Background

Pharmaceutical Assistance (PA) is a dynamic and multidisciplinary process that aims to supply health systems, programs or services with quality medicines, enabling access and health care, in an efficient and timely manner. The objective of the study was to evaluate the profile of administrative processes for the treatment of PsA, identify the time elapsed in the flow of processes and its associated factors.

Methods

A cross-sectional study of medication requests for the treatment of PsA was carried out between November 2014 and December 2016. Linear regression was used to verify the factors associated with time to delivery.

Results

A total of 218 cases containing 250 drugs were analyzed. The median time between the medical appointment and the first dispensation was 66 days (interquartile range, 44–90). The State proceedings, which includes requesting the drug until the authorization of treatment, was the stage that most contributed to the total time spent. The factors associated with the longer time to delivery of medications were prescriptions coming from clinics and specialty centers, from dermatologists, non-authorized processes and non-persistent patients in the treatment in 12 months.

Conclusion

The median time to receive medicines for the PsA treatment in Belo Horizonte health region after a medical prescription was higher than 2 months. The time between the solicitation of the medicines and the authorization of the treatment in the SUS (State administrative procedure) was the main component of the total time spent.
An investigation into factors that determine the growth rate in the Islamic banking and finance
Authors: Nawaz Huma
Published: November 2019

The purpose of this study is to determine the impact of products and services of Islamic finance in Pakistan. This study has involved an empirical analysis of the environmental factors of growth and its impact on the growth of Islamic Financial Institutions. To investigate the factors of growth, a structural equation model develops that incorporates the main determinants of growth of banking assets and equity funds. The growth in the Islamic equity funds and banking assets has been identified as definite antecedents of growth in the Islamic financial system. The empirical investigation by the structural model using Pakistani dataset revealed that four out of ten hypotheses were significant including two direct paths as antecedents of annual growth. This study provides empirical support for the influence of some development factors to control the barriers of growth in the Islamic finance industry. This paper allows the identification of the major development factors of Islamic financial system that takes into account the importance of operational strategy and environment for the growth of Islamic equity funds and banking assets.
Neurokinin 3 Receptor Antagonists Do Not Increase FSH or Estradiol Secretion in Menopausal Women
Authors: Prague Julia K , Abbara Ali , Comninos Alexander N , Jayasena Channa N , Higham Claire E , Adaway Jo , Keevil Brian G , Veldhuis Johannes D , Dhillo Waljit S
Published: November 2019

Background

Neurokinin 3 receptor (NK3R) antagonism is a promising novel treatment for menopausal flashes. However, to avoid adverse hormonal effects it is clinically important to first confirm whether gonadotropin and estradiol concentrations change as a result of their administration.

Methods

Single-center, randomized, double-blind, placebo-controlled, crossover trial of an oral NK3R antagonist (MLE4901) in 28 women aged 40 to 62 years, experiencing >7 hot flashes/24 h; some bothersome or severe (Clinicaltrials.gov, NCT02668185). Weekly serum gonadotropins and estradiol levels were measured using commercially available automated immunoassays a priori. Serum estradiol was also measured post hoc using a highly sensitive direct assay by liquid chromatography tandem mass spectrometry. Hormone levels were compared by the paired sample t tests or by the Wilcoxon matched-pairs signed rank test, as appropriate for the distribution of the data.

Results

Mean (standard deviation) serum follicle-stimulating hormone (FSH) concentration was not significantly increased when taking MLE4901 (72.07 ± 19.81 IU/L) compared to placebo (70.03 ± 19.56 IU/L), P = .26. Serum estradiol was also not significantly altered, irrespective of which assay method was used (median interquartile range of serum estradiol by immunoassay: placebo 36 ± 3 pmol/L, MLE4901 36 ± 1 pmol/L, P = .21; median serum highly sensitive estradiol: placebo 12 ± 16 pmol/L, MLE4901 13 ± 15 pmol/L, P = .70). However, mean (standard deviation) serum luteinizing hormone concentration significantly decreased with MLE4901 (27.63 ± 9.76 IU/L) compared to placebo (30.26 ± 9.75 IU/L), P = .0024.

Implication

NK3R antagonists do not increase serum estradiol or FSH despite their reduction in hot flashes. This is clinically significant and highly reassuring for women who have a contraindication to conventional hormone therapy such as prior/existing breast cancer and/or thromboembolism.
A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress
Authors: Rissone Alberto , Jimenez Erin , Bishop Kevin , Carrington Blake , Slevin Claire , Wincovitch Stephen M. , Sood Raman , Candotti Fabio , Burgess Shawn M.
Published: November 2019

Mutations in the gene AK2 are responsible for Reticular Dysgenesis (RD), a rare and severe form of primary immunodeficiency in children. RD patients have a severely shortened life expectancy and without treatment die, generally from sepsis early after birth. The only available therapeutic option for RD is hematopoietic stem cell transplantation (HSCT). To gain insight into the pathophysiology of RD, we previously created zebrafish models for AK2 deficiencies. One of the clinical features of RD is hearing loss, but its pathophysiology and causes have not been determined. In adult mammals, sensory hair cells of the inner ear do not regenerate; however, their regeneration has been observed in several non-mammalian vertebrates, including zebrafish. Therefore, we used our RD zebrafish models to determine if AK2 deficiency affects sensory organ development and/or hair cell regeneration. Our studies indicated that AK2 is required for the correct development, survival and regeneration of sensory hair cells. Interestingly, AK2 deficiency induces the expression of several oxidative stress markers and it triggers an increased level of cell death in the hair cells. Finally, we show that glutathione treatment can partially rescue hair cell development in the sensory organs in our RD models, pointing to the potential use of antioxidants as a therapeutic treatment supplementing HSCT to prevent or ameliorate sensorineural hearing deficits in RD patients.
Predictive statistical model for the factors associated with prenatal depression among pregnant adolescents in Maha Sarakham province, Thailand
Authors: Jantasin Bhanwasa , Yoosook Witaya , Thaewpia Supawadee
Published: November 2019

Background: The rate of adolescent pregnancy has steadily increased in Thailand over the years and depression is considered an important psychological problem in many pregnant adolescents. The aims of this study were to determine the proportion of pregnant adolescents with depressive symptoms and to identify a predictive statistical model for the factors related to prenatal depression among adolescents at antenatal care clinics in 10 community health centers in Maha Sarakham Province.

Methods: A cross-sectional study was conducted in 230 randomly selected participants who were pregnant adolescents who volunteered to participate in the research, those aged ≤19 years, and had an estimated gestational age of ≤18 weeks. Those with severe obstetrics complications or a psychiatric disorder were excluded. The subjects were asked to complete a demographic questionnaire and the Thai version of the Edinburgh Postnatal Depression Scale. The mean age of participants was 17.0 (±1.4) years.

Results: Overall, 43.9% of the adolescents had a cut off score of ≥11, suggestive of prenatal depressive symptoms. Multivariate analysis identified that pregnant adolescents at a primary school education level were 6.5 times more likely to experience depression symptoms than those with a diploma. Those who were emotionally supported by their husband or partner compared to relatives had a five times higher chance of presenting depressive symptoms, and those with a perceived bad relationship with their husband or partner seven times higher. The model was well-calibrated (goodness-of-fit test, p = 0.675) and had high discriminative power (ROC curve = 0.73 (95%CI = 0.67 to 0.79).

Conclusions: More attention is needed to reduce the known problems with pregnant adolescents and to ensure they continue with their education.  Lastly, public education to support mental health initiatives for individuals and families should be encouraged.