Gene expression of circulating tumour cells and its correlation with tumour stage in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Breast cancer (BC) represents one of the leading causes of cancer related deaths worldwide. New tools for diagnostic staging and therapeutic monitoring are needed to improve individualized therapies and improve clinical outcome. The analyses of circulating tumour cells may provide important prognostic information in the clinical setting.</p> <p>Materials and methods</p> <p>Circulating tumour cells (CTC) of 63 BC patients were isolated from peripheral blood (PB) through immunomagnetic separation. Subsequently, RT-PCR or mPCR for the genes <it>ga733.2</it>, <it>muc-1</it>, <it>c-erbB2</it>, <it>mgb-1</it>, <it>spdef </it>and <it>c-erbB2 </it>were performed. Subsequently, expression data were correlated with the tumour stages. Fourteen healthy individuals served as controls.</p> <p>Results</p> <p>Significant correlations with tumour stages were found in single gene analyses of <it>ga733.2</it>, <it>muc-1 </it>and in multi-gene analyses of <it>ga733.2</it>/<it>muc-1</it>/<it>mgb1</it>/<it>spdef</it>. Furthermore, a significant correlation of <it>Ca 15-3 </it>and all studied genes was also observed.</p> <p>Conclusion</p> <p>Herein, we demonstrated a positive correlation of a gene signature consisting of <it>ga733.2</it>, <it>muc-1</it>, <it>mgb1 </it>and <it>spdef </it>and advanced stages of BC. Moreover, all studied genes and gene patterns revealed a significant correlation with <it>Ca 15-3 </it>positive cases.</p

Co-opetition models for governing professional football

In recent years, models for co-creating value in a business-to-business context have often been examined with the aim of studying the strategies implemented by and among organisations for competitive and co-operative purposes. The traditional concepts of competition and co-operation between businesses have now evolved, both in terms of the sector in which the businesses operate and in terms of the type of goods they produce. Many researchers have, in recent times, investigated the determinants that can influence the way in which the model of co-opetition can be applied to the football world. Research interest lies in the particular features of what makes a good football. In this paper, the aim is to conduct an analysis of the rules governing the “football system”, while also looking at the determinants of the demand function within football entertainment. This entails applying to football match management the co-opetition model, a recognised model that combines competition and co-operation with the view of creating and distributing value. It can, therefore, be said that, for a spectator, watching sport is an experience of high suspense, and this suspense, in turn, depends upon the degree of uncertainty in the outcome. It follows that the rules ensuring that both these elements can be satisfied are a fertile ground for co-operation between clubs, as it is in the interest of all stakeholders to offer increasingly more attractive football, in comparison with other competing products. Our end purpose is to understand how co-opetition can be achieved within professional football

Optical simulations and optimization of perovskite/CI(G)S tandem solar cells using the transfer matrix method

In this work we employ the transfer matrix method for the analysis of optical materials properties to simulate and optimize monolithic tandem solar cell devices based on CuIn$_{1−x}$Ga$_x$Se$_2$, CI(G)S, and perovskite (PVK) absorbers. By finding models that fit well the experimental data of the CI(G)S solar cell, the semitransparent perovskite solar cell (PSC) and the PVK/CI(G)S monolithic tandem solar cell, we were able to perform a detailed optical loss analysis that allowed us to determine sources of parasitic absorption. We found better substitute materials for the transport layers to increase the power conversion efficiency and, in case of semitransparent PSCs, sub-bandgap transmittance. Our results set guidelines for the monolithic PVK/CI(G)S tandem solar cells development, predicting an achievable efficiency of 30%

Corrective osteotomies in the treatment of lower limb deformities in deforming osteoarthritis of the knee joint

The paper presents the medium-term results of the use of periarticular osteotomies of the tibia and femur in the treatment of deforming knee arthrosis (KA) against the background of lower limb deformities. The aim of the study was to evaluate the effectiveness of osteotomy combined with one-stage endoscopic organsparing interventions in the treatment of gonarthrosis. The object of the study was 74 patients with deforming osteoarthritis (DOA) of KA II-III degrees. Selection criteria: changes in the load axis of the limb in the frontal and sagittal planes, degenerative changes of the joint predominantly in one department (medial, lateral), the presence of contracture not more than 10˚. The study group did not include patients with degenerative damage to two parts of the knee joint, pronounced patellofemoral arthrosis, and flexion contracture of more than 10°. Preoperative planning and selection were performed on the basis of clinical examination, radiography, MRI, and CT scan data. Surgical treatment was performed in one surgical session: when correcting a varus deformity, osteotomy was performed first, and arthroscopic intervention, including ligament plasty, was performed second; when correcting a valgus deformity with femoral osteotomy, primary KA arthroscopy followed by osteotomy was optimal. As a result of the treatment, excellent and good results were achieved in the majority of patients in the medium-term periodАннотация В работе представлены среднесрочные результаты использования околосуставных остеотомий большеберцовой и бедренной кости при лечении деформирующего артроза коленного сустава (КС) на фоне деформаций нижних конечностей. Задачей исследования была оценка эффективности остеотомии в сочетании с одноэтапными эндоскопическими органо-сберегающими вмешательствами при лечении гонартроза. Объект исследования — 74 пациента с деформирующим остеоартрозом (ДОА) КС II-III степеней. Критерии отбора: изменения нагрузочной оси конечности во фронтальной и сагиттальной плоскостях, дегенеративные изменения сустава преимущественно в одном из отделов (медиальный, латеральный), наличие контрактуры не более 10°. В группу исследования не вошли пациенты с дегенеративными повреждениями двух отделов коленного сустава, выраженным пателлофеморальным артрозом, сгибательной контрактурой более 10°. Предоперационное планирование и отбор проводили на основании данных клинического обследования, рентгенографии, МРТ, КТ. Оперативное лечение выполняли в одну хирургическую сессию: при коррекции варусной деформации первым этапом выполняли остеотомию, вторым — артроскопическое вмешательство, включая пластику связок при коррекции вальгусной деформации с остеотомией бедра, оптимальна первичная артроскопия КС с последующей остеотомией. В результате проведенного лечения у большинства пациентов в среднесрочном периоде достигнуты отличные и хорошие результат

Modern solutions in reconstruction of the anterior cruciate ligament

The rapid development of medical technologies makes the attitude to anterior cruciate ligament (ACL) reconstruction constantly reconsidered. In our work, we evaluated the results of surgical treatment of patients after ACL reconstruction using different options of graft fixation. We retrospectively analyzed the treatment of 125 patients with anterior instability of the knee joint. No great difference in the results of choosing the method of ACL graft fixation was revealed. The «all-inside» technology seems more promising. Correct positioning of the bone canals is very important. In the case of simultaneous meniscus injury it is necessary to perform a suture in order to preserve an important passive stabilizer of the knee jointБурное развитие медицинских технологий заставляет постоянно пересматривать отношение к реконструкции передней крестообразной связки (ПКС). В своей работе мы оценивали результаты оперативного лечения пациентов после восстановления ПКС с использованием различных вариантов фиксации трансплантата. Был выполнен ретроспективный анализ лечения 125 пациентов с передней нестабильностью коленного сустава. Большой разницы в результатах при выборе метода фиксации трансплантата ПКС не было выявлено. Технология all-inside представляется более перспективной. Очень важное значение имеет правильное позиционирование костных каналов. В случае симультанного повреждения мениска необходимо выполнять шов с целью сохранения важного пассивного стабилизатора коленного сустав

Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes

Propionibacterium acnes (P. acnes) has been known to produce various exogenous proteases, however, their role in acne pathogenesis remains largely unknown. Proteases elicit cellular responses, at least in part, via proteinase-activated receptor-2 (PAR-2), which is known to mediate inflammation and immune response. In this study, we investigated whether proteases from P. acnes could activate PAR-2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR-2 expression and protease activity in acne lesions using immunofluorescence staining and in situ zymography. The effect of the culture supernatant of P. acnes on Ca2+ signaling in immortalized keratinocytes (HaCaT) was measured using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC 6919 culture supernatant, with or without pretreatment with serine protease inhibitor or selective PAR-2 antagonist and the gene expression of pro-inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse transcription-polymerase chain reaction. We found that the protease activity and PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA expression of interleukin (IL)-1α, -8, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes, which was significantly inhibited by serine protease inhibitor as well as selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes

Control of Propionibacterium acnes by natural antimicrobial substances: Role of the bacteriocin AS-48 and lysozyme

We report the high susceptibility of several clinical isolates of Propionibacterium acnes from different sources (skin, bone, wound exudates, abscess or blood contamination) to the head-to-tail cyclized bacteriocin AS-48. This peptide is a feasible candidate for further pharmacological development against this bacterium, due to its physicochemical and biological characteristics, even when it is growing in a biofilm. Thus, the treatment of pre-formed biofilms with AS-48 resulted in a dose- and time-dependent disruption of the biofilm architecture beside the decrease of bacterial viability. Furthermore, we demonstrated the potential of lysozyme to bolster the inhibitory activity of AS-48 against P. acnes, rendering high reductions in the MIC values, even in matrix-growing cultures, according to the results obtained using a range of microscopy and bioassay techniques. The improvement of the activity of AS-48 through its co-formulation with lysozyme may be considered an alternative in the control of P. acnes, especially after proving the absence of cytotoxicity demonstrated by these natural compounds on relevant human skin cell lines. In summary, this study supports that compositions comprising the bacteriocin AS-48 plus lysozyme must be considered as promising candidates for topical applications with medical and pharmaceutical purposes against dermatological diseases such as acne vulgaris.This research was funded by a grant from the Spanish Ministry of Economy and Competitiveness (SAF2013-48971-C2-1-R that included funds from European Regional Development, ERDF), and the Research Group General (BIO160, UGR)

Differential Attraction of Malaria Mosquitoes to Volatile Blends Produced by Human Skin Bacteria

The malaria mosquito Anopheles gambiae sensu stricto is mainly guided by human odour components to find its blood host. Skin bacteria play an important role in the production of human body odour and when grown in vitro, skin bacteria produce volatiles that are attractive to A. gambiae. The role of single skin bacterial species in the production of volatiles that mediate the host-seeking behaviour of mosquitoes has remained largely unknown and is the subject of the present study. Headspace samples were taken to identify volatiles that mediate this behaviour. These volatiles could be used as mosquito attractants or repellents. Five commonly occurring species of skin bacteria were tested in an olfactometer for the production of volatiles that attract A. gambiae. Odour blends produced by some bacterial species were more attractive than blends produced by other species. In contrast to odours from the other bacterial species tested, odours produced by Pseudomonas aeruginosa were not attractive to A. gambiae. Headspace analysis of bacterial volatiles in combination with behavioural assays led to the identification of six compounds that elicited a behavioural effect in A. gambiae. Our results provide, to our knowledge, the first evidence for a role of selected bacterial species, common on the human skin, in determining the attractiveness of humans to malaria mosquitoes. This information will be used in the further development of a blend of semiochemicals for the manipulation of mosquito behaviour

First Evidence of Reproductive Adaptation to “Island Effect” of a Dwarf Cretaceous Romanian Titanosaur, with Embryonic Integument In Ovo

<div><h3>Background</h3><p>The Cretaceous vertebrate assemblages of Romania are famous for geographically endemic dwarfed dinosaur taxa. We report the first complete egg clutches of a dwarf lithostrotian titanosaur, from Toteşti, Romania, and its reproductive adaptation to the “island effect”.</p> <h3>Methodology/Findings</h3><p>The egg clutches were discovered in sequential sedimentary layers of the Maastrichtian Sânpetru Formation, Toteşti. The occurrence of 11 homogenous clutches in successive strata suggests philopatry by the same dinosaur species, which laid clutches averaging four ∼12 cm diameters eggs. The eggs and eggshells display numerous characters shared with the positively identified material from egg-bearing level 4 of the Auca Mahuevo (Patagonia, Argentina) nemegtosaurid lithostrotian nesting site. Microscopic embryonic integument with bacterial evidences was recovered in one egg. The millimeter-size embryonic integument displays micron size dermal papillae implying an early embryological stage at the time of death, likely corresponding to early organogenesis before the skeleton formation.</p> <h3>Conclusions/Significance</h3><p>The shared oological characters between the Haţeg specimens and their mainland relatives suggest a highly conservative reproductive template, while the nest decrease in egg numbers per clutch may reflect an adaptive trait to a smaller body size due to the “island effect”. The combined presence of the lithostrotian egg and its embryo in the Early Cretaceous Gobi coupled with the oological similarities between the Haţeg and Auca Mahuevo oological material evidence that several titanosaur species migrated from Gondwana through the Haţeg Island before or during the Aptian/Albian. It also suggests that this island might have had episodic land bridges with the rest of the European archipelago and Asia deep into the Cretaceous.</p> </div