The electronic structure, surface properties, and in situ N2O decomposition of mechanochemically synthesised LaMnO3

The use of mechanochemistry to prepare catalytic materials is of significant interest; it offers an environmentally beneficial, solvent-free, route and produces highly complex structures of mixed amorphous and crystalline phases. This study reports on the effect of milling atmosphere, either air or argon, on mechanochemically prepared LaMnO3 and the catalytic performance towards N2O decomposition (deN2O). In this work, high energy resolution fluorescence detection (HERFD), X-ray absorption near edge structure (XANES), X-ray emission, and X-ray photoelectron spectroscopy (XPS) have been used to probe the electronic structural properties of the mechanochemically prepared materials. Moreover, in situ studies using near ambient pressure (NAP)-XPS, to follow the materials during catalysis, and high pressure energy dispersive EXAFS studies, to mimic the preparation conditions, have also been performed. The studies show that there are clear differences between the air and argon milled samples, with the most pronounced changes observed using NAP-XPS. The XPS results find increased levels of active adsorbed oxygen species, linked to the presence of surface oxide vacancies, for the sample prepared in argon. Furthermore, the argon milled LaMnO3 shows improved catalytic activity towards deN2O at lower temperatures compared to the air milled and sol-gel synthesised LaMnO3. Assessing this improved catalytic behaviour during deN2O of argon milled LaMnO3 by in situ NAP-XPS suggests increased interaction of N2O at room temperature within the O 1s region. This study further demonstrates the complexity of mechanochemically prepared materials and through careful choice of characterisation methods how their properties can be understood

Forensic age diagnostics by magnetic resonance imaging of the proximal humeral epiphysis

The most commonly used radiological method for age estimation of living individuals is X-ray. Computed tomography is not commonly used due to high radiation exposure, which raises ethical concerns. This problem can be solved with the use of magnetic resonance imaging (MRI), which avoids the use of ionizing radiation. The purpose of the present study was to evaluate the utility of MRI analysis of the proximal humeral epiphyses for forensic age estimations of living individuals. In this study, 395 left proximal humeral epiphyses (patient age 12-30years) were evaluated with fast-spin-echo proton density-weighted image (FSE PD) sequences in a coronal oblique orientation on shoulder MRI images. A five-stage scoring system was used following the method of Dedouit et al. The intra- and interobserver reliabilities assessed using Cohen's kappa statistic were =0.818 and =0.798, respectively. According to this study, stage five first appeared at 20 and 21years of age in males and females, respectively. These results are not directly comparable to any other published study due to the lack of MRI data on proximal humeral head development. These findings may provide valuable information for legally important age thresholds using shoulder MRI. The current study demonstrates that MRI of the proximal humerus can support forensic age estimation. Further research is needed to establish a standardized protocol that can be applied worldwide

Applicability of T1-weighted MRI in the assessment of forensic age based on the epiphyseal closure of the humeral head

This work investigates the value of magnetic resonance imaging analysis of proximal epiphyseal fusion in research examining the growth and development of the humerus and its potential utility in establishing forensic age estimation. In this study, 428 proximal humeral epiphyses (patient age, 12-30years) were evaluated with T1-weighted turbo spin echo (T1 TSE) sequences in coronal oblique orientation on shoulder MRI images. A scoring system was created following a combination of the Schmeling and Kellinghaus methods. Spearman's rank correlation analysis revealed a significant positive relationship between age and ossification stage of the proximal humeral epiphysis (all subjects: rho=0.664, p<0.001; males: 0.631, p<0.001; females: rho=0.651, p<0.001). The intra- and inter-observer reliability assessed using Cohen's kappa statistic was =0.898 and =0.828, respectively. The earliest age of epiphysis closure was 17years for females and 18years for males. MRI of the proximal humeral epiphysis can be considered advantageous for forensic age estimation of living individuals in a variety of situations, ranging from monitoring public health to estimating the age of illegal immigrants/asylum seekers, minors engaged in criminal activities, and illegal participants in competitive sports, without the danger of radiation exposure

The partial oxidation of methane over Pd/Al2O3 catalyst nanoparticles studied in-situ by near ambient-pressure x-ray photoelectron spectroscopy

Near ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) is used to study the chemical state of methane oxidation catalysts in-situ. Al2O3{supported Pd catalysts are prepared with different particle sizes ranging from 4 nm to 10 nm. These catalysts were exposed to conditions similar to those used in the partial oxidation of methane (POM) to syn-gas and simultaneously monitored by NAP-XPS and mass spectrometry. NAP-XPS data show changes in the oxidation state of the palladium as the temperature in- creases, from metallic Pd0 to PdO, and back to Pd0. Mass spectrometry shows an increase in CO production whilst the Pd is in the oxide phase, and the metal is reduced back under presence of newly formed H2. A particle size effect is observed, such that CH4 conversion starts at lower temperatures with larger sized particles from 6 nm to 10 nm. We find that all nanoparticles begin CH4 conversion at lower temperatures than polycrystalline Pd foil

Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abstract Introduction Evaluating the expression of signaling molecule proteins from the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol-3-kinase (PI3K) pathway in invasive breast cancers may identify prognostic marker(s) associated with early relapse. Methods Immunohistochemical analyses of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), PI3K-p110α, phospho-AKT, phospho-p70S6 kinase, phospho-S6 ribosomal protein, phospho-RAF, phospho-p44/42 MAPK, and heat-shock protein 90 (HSP90) were performed on tumor samples from 212 patients with invasive breast cancer. Statistically significant relations between protein expression, clinicopathologic factors, and relapse-free survival (RFS) were analyzed. Results Expression of HSP90 was associated with 5-year RFS, as well as T stage, N stage, histologic grade, estrogen receptor (ER) expression, human epidermal growth factor receptor 2 (HER2) expression, and the Ki-67 proliferation index. On multivariate analysis, coexpression of HSP90 and PI3K-p110α or expression of HSP90 along with PTEN loss demonstrated significantly worse RFS. In subgroup analyses, both exhibited strong prognostic significance in HER2-positive cases, but not in HER2-negative cases. Conclusions The coexpression of HSP90 with PI3K-p110α or expression of HSP90 along with PTEN loss has a potential as a molecular prognostic marker to predict early relapse in patients with invasive breast cancers

The disease-specific clinical trial network for primary ciliary dyskinesia: PCD-CTN

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by impaired mucociliary clearance leading to irreversible lung damage. In contrast to other rare lung diseases like cystic fibrosis (CF), there are only few clinical trials and limited evidence-based treatments. Management is mainly based on expert opinions and treatment is challenging due to a wide range of clinical manifestations and disease severity. To improve clinical and translational research and facilitate development of new treatments, the clinical trial network for PCD (PCD-CTN) was founded in 2020 under the framework of the European Reference Network (ERN)-LUNG PCD Core. Applications from European PCD sites interested in participating in the PCD-CTN were requested. Inclusion criteria consisted of patient numbers, membership of ERN-LUNG PCD Core, use of associated standards of care, experience in PCD and/or CF clinical research, resources to run clinical trials, good clinical practice (GCP) certifications and institutional support. So far, applications from 22 trial sites in 18 European countries have been approved, including >1400 adult and >1600 paediatric individuals with PCD. The PCD-CTN is headed by a coordinating centre and consists of a steering and executive committee, a data safety monitoring board and committees for protocol review, training and standardisation. A strong association with patient organisations and industrial companies are further cornerstones. All participating trial sites agreed on a code of conduct. As CTNs from other diseases have demonstrated successfully, this newly formed PCD-CTN operates to establish evidence-based treatments for this orphan disease and to bring new personalised treatment approaches to patients

Cyprus women's health research (COHERE) initiative: determining the relative burden of women's health conditions and related co-morbidities in an Eastern Mediterranean population

Background: There is lack of population level data on prevalence and distribution of common benign women's health conditions such as endometriosis, uterine fibroids, polycystic ovary syndrome from the Eastern Mediterranean region despite their significant consequences on quality of life. In particular, there is complete absence of any health statistics from Northern Cyprus, which is an emerging region in Europe. The Cyprus Women's Health Research (COHERE) Initiative is the first large-scale cross-sectional study in the region, aiming to determine the relative burden of benign women's health conditions and related co-morbidities in women living in Northern Cyprus. Methods: The COHERE Initiative is a cross-sectional study aiming to recruit 8000 women aged 18 55 years and residing for at least the past 5 years in Northern Cyprus. The study is composed of two main steps: (1) Baseline recruitment, including (i) completion of a detailed health questionnaire, which is an expanded version of the World Endometriosis Research Foundation (WERF) Endometriosis Phenome Harmonisation Project (EPHect) standardised questionnaire, including questions on demographics, menstrual history, hormone use, pregnancy, pain (pelvic pain, bladder and bowel pain, migraine), medical history, family history of illnesses, medication use, life-style factors in relation to a wide range of reproductive and endocrine conditions, resource use (ii) measurement of weight, height, waist/hip circumference and blood pressure, (iii) collection of saliva samples for genotyping. (2) Gynaecology clinic follow up, including a pelvic ultrasound scan (USS). There is also a follow-up food frequency questionnaire (FFQ) targeted to all women taking part in the baseline recruitment with an aim to collect more detailed data on dietary habits. Discussion: The COHERE Initiative will generate prevalence rates for conditions, define the clinical profiles for women's health conditions, and estimate the economic burden of these conditions in Northern Cyprus. The results will also provide insights into the current status of health-care among women living in a currently under-investigated region. The genetic findings will inform future gene mapping studies for investigation of the heritable component of conditions in this population/region. Moreover, the results will be compared with other centres collecting data using EPHect tools globally and will help determine population differences and similarities in disease patterns and clinical profiles. The COHERE Initiative will serve as a resource to conduct hypothesis-driven follow-up studies investigating effect of the Mediterranean life-style' as well as genetic factors on common benign women's health conditions that maybe specific to Eastern Mediterranean populations

High efficiency of alphaviral gene transfer in combination with 5-fluorouracil in a mouse mammary tumor model

Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: The combination of virotherapy and chemotherapy may enable efficient tumor regression that would be unachievable using either therapy alone. In this study, we investigated the efficiency of transgene delivery and the cytotoxic effects of alphaviral vector in combination with 5-fluorouracil (5-FU) in a mouse mammary tumor model (4 T1).Methods: Replication-deficient Semliki Forest virus (SFV) vectors carrying genes encoding fluorescent proteins were used to infect 4 T1 cell cultures treated with different doses of 5-FU. The efficiency of infection was monitored via fluorescence microscopy and quantified by fluorometry. The cytotoxicity of the combined treatment with 5-FU and alphaviral vector was measured using an MTT-based cell viability assay. In vivo experiments were performed in a subcutaneous 4 T1 mouse mammary tumor model with different 5-FU doses and an SFV vector encoding firefly luciferase.Results: Infection of 4 T1 cells with SFV prior to 5-FU treatment did not produce a synergistic anti-proliferative effect. An alternative treatment strategy, in which 5-FU was used prior to virus infection, strongly inhibited SFV expression. Nevertheless, in vivo experiments showed a significant enhancement in SFV-driven transgene (luciferase) expression upon intratumoral and intraperitoneal vector administration in 4 T1 tumor-bearing mice pretreated with 5-FU: here, we observed a positive correlation between 5-FU dose and the level of luciferase expression.Conclusions: Although 5-FU inhibited SFV-mediated transgene expression in 4 T1 cells in vitro, application of the drug in a mouse model revealed a significant enhancement of intratumoral transgene synthesis compared with 5-FU untreated mice. These results may have implications for efficient transgene delivery and the development of potent cancer treatment strategies using alphaviral vectors and 5-FU.publishersversionPeer reviewe

Cardiovascular development: towards biomedical applicability: Epicardium-derived cells in cardiogenesis and cardiac regeneration

During cardiogenesis, the epicardium grows from the proepicardial organ to form the outermost layer of the early heart. Part of the epicardium undergoes epithelial-mesenchymal transformation, and migrates into the myocardium. These epicardium- derived cells differentiate into interstitial fibroblasts, coronary smooth muscle cells, and perivascular fibroblasts. Moreover, epicardium-derived cells are important regulators of formation of the compact myocardium, the coronary vasculature, and the Purkinje fiber network, thus being essential for proper cardiac development. The fibrous structures of the heart such as the fibrous heart skeleton and the semilunar and atrioventricular valves also depend on a contribution of these cells during development. We hypothesise that the essential properties of epicardium-derived cells can be recapitulated in adult diseased myocardium. These cells can therefore be considered as a novel source of adult stem cells useful in clinical cardiac regeneration therapy

Cannulated screw and hexapodal fixator reconstruction for compound upper tibial fractures

OBJECTIVES: The aim of the treatment of tibial plateau fractures is to obtain a pain-free and fully functional knee with closed reduction, percutaneous cannulated screw fixation and hexapodal external fixator reconstruction for high energy compound upper tibial fractures. METHODS: Patients with comminuted tibial plateau fractures underwent closed reduction, percutaneous fixation with cannulated screws, and reconstruction with hexapodal external fixator. The follow-up period was 24 months. RESULTS: The clinical and radiological results were good or excellent. The average knee flexion was 125°. CONCLUSION: Our results are successful in the initial stage, however, it should be pointed out that during the long term follow-up osteoarthritis may develop leading to worsening of the condition. Level of Evidence IV, Case Series