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Atopic dermatitis (AD), or eczema, is a common skin disease that is often associated with other atopic disorders, such as allergic rhinitis and asthma. The disease can develop both in infancy and adulthood, and characterizes with recurrent episodes impairing the quality of life. The review аnalyzes the genetical, immunological, and environmental factors in the pathogenesis of AD. The role of the skin barrier function is also considered in regard of the main hypotheses for AD development. Further elucidation of the mechanisms involved in the pathogenesis of AD could give interesting and useful clues for therapeutic protocols and prophylactic approaches.

Background Gaps between clinical guidelines and attainment of LDL-C goals are evident across jurisdictions. Despite strong evidence of benefit from PCSK9-inhibitors (PCSK9i) treatment in eligible patients, significant underuse remains, suggesting considerable unmet need in clinical outcomes optimization. Purpose We investigated key performance endpoints across 10 countries to provide a comparative assessment of potential barriers in PCSK9i therapeutic integration from a healthcare system perspective. Methods We performed secondary analysis of peer-reviewed literature, health technology assessment reports, guidelines, clinical pathways since 2015 and constructed a comparative framework of pre-defined endpoints for 10 study countries (Japan, Italy, Spain, Australia, Canada, United Kingdom, Germany, France, Netherlands, USA). We identified 8 endpoints, which were clustered in 3 domains: (a) healthcare system characteristics, (b) demand-side policies, (c) medicine reimbursement policies, pertaining to cost-sharing. Approved PCSK9i indications were in scope. Results PCSK9i are reimbursed in all countries. Prescribing restrictions have been applied in all countries (Table 1). PCSK9i for primary prevention are reimbursed mainly in familial hypercholesterolemia, while additional criteria may apply depending on country and condition. PCSK9i are: (a) reserved mainly for very high- or high-risk cohorts (Japan, UK, Netherlands); (b) reimbursed for secondary prevention when additional risk factors/comorbidities exist (Australia, Germany, Netherlands); (c) recommended as 3rd line in 6 countries, as 2nd line in 3 and alone or in combination with other therapies in the USA; and (d) restricted to specialist prescribing while general practitioners cannot initiate treatment in 6 countries, potentially increasing waiting times and underuse rates. Follow-up periods may apply prior to establishing eligibility and vary from 3–12 months, while prior authorization/eligibility documentation may be necessary adding to administrative burden. Age criteria may apply in determining or continuing reimbursement (e.g. max 80 years in Italy). Regional and insurance plan variations apply in Canada and USA, respectively. LDL-C reimbursement thresholds are applied in 7 countries. Their relevance to guideline-recommended goals suggests potential underuse gaps (Fig. 1). While no threshold applies in Germany, an additional criterion of indication for LDL-apheresis determines eligibility. Cost-sharing ranges between 0–30% in co-insurance models, may include a flat fee, a deductible or combination of these. Conclusion Restrictions in the use of PCSK9i from marketing authorization labels are implemented in all 10 countries and differ across key endpoints. Significant differences exist between guideline-recommended LDL-C goals and reimbursement thresholds, while additional prescribing and documentation restrictions apply over reimbursed indications, contributing to potential underuse. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen Inc.

Geospace plasma simulations have progressed toward more realistic descriptions of the solar wind-magnetosphere interaction from magnetohydrodynamic to hybrid ion-kinetic, such as the state-of-the-art Vlasiator model. Despite computational advances, electron scales have been out of reach in a global setting. eVlasiator, a novel Vlasiator submodule, shows for the first time how electromagnetic fields driven by global hybrid-ion kinetics influence electrons, resulting in kinetic signatures. We analyze simulated electron distributions associated with reconnection sites and compare them with Magnetospheric Multiscale (MMS) spacecraft observations. Comparison with MMS shows that key electron features, such as reconnection inflows, heated outflows, flat-top distributions, and bidirectional streaming, are in remarkable agreement. Thus, we show that many reconnection-related features can be reproduced despite strongly truncated electron physics and an ion-scale spatial resolution. Ion-scale dynamics and ion-driven magnetic fields are shown to be significantly responsible for the environment that produces electron dynamics observed by spacecraft in near-Earth plasmas.

Supply chain is a crucial part of the world economy and everyday life. During the outbreak of COVID-19 in 2020, governments across the globe have tried to maintain the supply chain operations in most of the essential goods and services. Dry bulk shipping, a sector characterized by trading versatility and a multitude of cargoes carried, has an important role to play towards that aim. Port restrictions, placed to limit the spread of COVID-19, have created the impression that the market of dry bulk shipping has, to some degree, been affected and become less predictable, as many other transporting services. In this article, this belief is investigated using both state space modeling and neural networks. In particular, using these methods, one-month ahead predictions (during 2020) of the overall freight cost are obtained for three types of vessels (representing the majority of the minor bulks industry). A good forecast performance is observed and this validates the models and the estimation methods proposed. Our results suggest that there is no significant effect of COVID-19 in these types of vessels and their operations. This can provide useful information to shipping managers and policy makers. © 2021 Taylor & Francis Group, LLC.

Background/Aim: Postsurgical hypoparathyroidism (PostHypo) is a common complication after total thyroidectomy. We studied the risk factors associated with PostHypo. Patients and Methods: The study included 109 women, (mean age: 50.7±10.75 years), who underwent total thyroidectomy for thyroid diseases. Results: Based on the development of biochemical hypocalcemia on the first postoperative day following total thyroidectomy, (cCa

The design of an autonomous underwater vehicle (AUV) with physical dimensions of 1100 mm × 700 mm × 330 mm, and weight of 55 kg, is introduced herein. This paper describes the design, materials, hydrodynamics, and system architecture of an AUV prototype named Synoris, developed as a low-cost and medium-scale testbed platform. Synoris moves via six brushless motors, can reach up to 200 m depth, has an autonomy estimated around 6 hours and a modular design for multiple payload options. Stability control, autonomous movement, obstacle avoidance temperature/pressure sensing, and video/image capturing are simultaneously performed by exploiting a set of onboard computers that are described briefly in Section 4. The whole platform is built on top of the open source software called ROS (robotic operating system) that provides a flexible framework for writing robot software by providing services such as low-level device control, message parsing, data fusion, and system integration. Synoris is ideal for underwater applications and missions, involving machine learning and computer vision features. AUV development in general meets high-cost solutions due to the complexity and harshness of the operational environment. Even the most cost-effective solutions demand plentiful resources. This paper describes the entire process of development and how a relatively low-cost approach can provide a reliable AUV for many underwater applications, involving AI and machine-learning capabilities.

Introduction: Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/β-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-β (Gsk3-β) and therefore induces Wnt/β-catenin signaling. Materials and methods: Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted. Results: Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six. Conclusion: The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model. © 2019 The Author(s).

What is known and objectivePolypharmacy has a significant impact on patients’ health with overall expenditure on over-the-counter (OTC) medicines representing a substantial burden in terms of cost of treatment. The aim of this study, which was conducted within the framework of a European Project funded by the European Union under the Seventh Framework Programme and was entitled OTC-SOCIOMED, was to report on possible determinants of patient behaviour regarding the consumption of medicines, and particularly OTCs, in the context of primary care. MethodsA multicentre, cross-sectional study was designed and implemented in well-defined primary healthcare settings in Cyprus, the Czech Republic, France, Greece, Malta and Turkey. Patients completed a questionnaire constructed on the basis of the theory of planned behaviour (TPB), which was administered via face-to-face interviews. Results and discussionThe percentage of patients who had consumed prescribed medicines over a 6-month period was consistently high, ranging from 79% in the Czech Republic and 82% in Turkey to 97% in Malta and 100% in Cyprus. Reported non-prescribed medicine consumption ranged from 33% in Turkey to 92% in the Czech Republic and 97% in Cyprus. TPB behavioural antecedents explained 43% of the variability of patients’ intention to consume medicines in Malta and 24% in Greece, but only 3% in Turkey. Subjective norm was a significant predictor of the intention to consume medicines in all three countries (Greece, Malta and Turkey), whereas attitude towards consumption was a significant predictor of the expectation to consume medicines, if needed. What is new and conclusionThis study shows that parameters such as patients’ beliefs and influence from family and friends could be determining factors in explaining the high rates of medicine consumption. Factors that affect patients’ behavioural intention towards medicine consumption may assist in the formulation of evidence-based policy proposals and inform initiatives and interventions aimed at increasing the appropriate use of medicines.

Study Objective Our study wishes to appraise the effectiveness of hands-on laparoscopic training sessions using visual analogue scales. Design Evaluation of training was performed via self and tutor assessment questionnaires using visual analogue scale of 10 cm length to measure pre and post-training scores. We measured 5 different skills considered essential in performing safe laparoscopic surgery: manual dexterity, needle handling, tissue handling and knot efficiency. In addition, we measured the ability tie specific laparoscopic knots: surgical, square, spaghetti, Watson. Scores were analyzed for statistical significance using student t-test. Setting Dry lab laparoscopic training boxes. Patients or Participants 9 trainees in Obstetrics and Gynecology, year 3 to 7 of training. Interventions One-day course based on theoretical lectures, video presentations and supervised practice in dry lab laparoscopic suturing. The ratio was one faculty to each two delegates. Measurements and Main Results There was a statistically significant difference in mean scores showing improvement for both candidate self-assessment and tutor assessment pre and post teaching session. The mean scores for generic skills were 3.7 to 5.8 for needle handling (P=0.000), 5.1 to 5.3 for dexterity (P=0.000), 4.8 to 5.3 for tissue handling (P=0.000), 0.3 to 3 for knot efficiency (P=0.000), 0.6 to 2.4 for knot tension (P=0.000). The mean scores recorded by faculty were similar. This was observed irrespective of the trainee's laparoscopic skills proficiency. Conclusion The perception of acquisition of skills and knowledge appears to be similar in candidate's and tutor's assessments. Feedback can quantify competence, confidence and the quality of the course. Although there are validated assessment tools for gynecological laparoscopic skills (SUTT from GESEA training program), there may be a place for simple, reproducible assessment tools for focused training sessions and specific skills development.

If the terabytes of Earth observation data currently stored in archives are published on the web using the linked data paradigm, data discovery, integration with other data sources, and the development of applications will become much easier. © 2017 IEEE.

There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20;mg qd and dabigatran 110;mg bid among patients with nonvalvular atrial fibrillation (NV-AF). We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively. Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P

Several biomolecules in Exhaled Breath Condensate (EBC) can be used as breath biomarkers providing useful clinical information concerning inflammatory lung diseases. Hydrogen peroxide has a special place among biomarkers as it can be directly linked to oxidative stress built up in the human body. Methods for hydrogen peroxide in EBC are essential for a vast number of studies spanning from basic studies to disease diagnosis. Methods currently in use are not automated, time-consuming and tedious. Moreover, most condensing equipment in use is not portable. To address these, we developed portable condensing equipment as an extra alternative and a fully automated Flow Injection (FI) - Chemiluminescence method for hydrogen peroxide determination. The proposed condensing equipment provides collection efficiency better than 86% allowing the collection of 2-3 mL sample in 20 min. The method involves mixing a luminol solution stream that is used as sample carrier with a cobalt(II) stream. Reaction of EBC with luminol in the presence of cobalt(II) catalyst produces light proportional to hydrogen peroxide concentration. The automated FI method features a 10 nmol L¹ detection limit and good linearity (r= 0.997). Precision and recoveries are better than 6.0% RSD and 64.9%, respectively. Comparison with the, commonly used for EBC, manual fluorimetric method showed no significant difference, P > 0.001, while correlation of the methods is high, r=0.94. The method provides automation in sample handling, sample throughput of 180 samples h¹ and low detection limit. Diversas biomoléculas analisadas na Condensação Respiratória Exalada (CRE) podem ser usadas como biomarcadoras, fornecendo informação clínica útil em doenças inflamatórias pulmonares. Peróxido de hidrogênio é um biomarcador especial, pois pode estar relacionado diretamente ao stress oxidativo gerado no corpo humano. Métodos para peróxido de hidrogênio em CRE são essenciais para um grande número de estudos, desde básicos até diagnósticos de doenças. Os métodos usados atualmente não são automatizados, são demorados e cansativos. Além disso, a maioria dos equipamentos de condensação não é portátil. Assim, desenvolvemos um equipamento portátil como uma alternativa extra e um método totalmente automático de injeção em fluxo (FI) com detecção por quimioluminescência para determinação de peróxido de hidrogênio. O equipamento proposto proporciona uma eficiência de coleta superior a 86%, permitindo coletar 2-3 mL de amostra em 20 min. O método envolve uma mistura em fluxo de solução de luminol como carregador da amostra com uma solução de cobalto(II). A reação de CRE com luminol na presença de cobalto(II) como catalisador produz luz proporcional à concentração de peróxido de hidrogênio. As características do método são limite de detecção de 10 nmol L¹ e boa linearidade (r= 0,997). Precisão e recuperações são melhores do que 6,0% RSD e 64,9%, respectivamente. A comparação com o método fluorimétrico manual, comumente usado para CRE, mostrou diferença não significativa, P > 0,001, enquanto a correlação entre os métodos é alta, r=0,94. O método proporciona automatização no manuseio avaliando 180 amostras h¹ e baixo limite de detecção.

Glutamate dehydrogenase (GDH) may be a stress-responsive enzyme, as GDH exhibits considerable thermal stability, and de novo synthesis of the α-GDH subunit is induced by exogenous ammonium and senescence. NaCl treatment induces reactive oxygen species (ROS), intracellular ammonia, expression of tobacco (Nicotiana tabacum cv Xanthi) gdh-NAD;A1 encoding the α-subunit of GDH, increase in immunoreactive α-polypeptide, assembly of the anionic isoenzymes, and in vitro GDH aminating activity in tissues from hypergeous plant organs. In vivo aminating GDH activity was confirmed by gas chromatorgraphy–mass spectrometry monitoring of 15N-Glu, 15N-Gln, and 15N-Pro in the presence of methionine sulfoximine and amino oxyacetic acid, inhibitors of Gln synthetase and transaminases, respectively. Along with upregulation of α-GDH by NaCl, isocitrate dehydrogenase genes, which provide 2-oxoglutarate, are also induced. Treatment with menadione also elicits a severalfold increase in ROS and immunoreactive α-polypeptide and GDH activity. This suggests that ROS participate in the signaling pathway for GDH expression and protease activation, which contribute to intracellular hyperammonia. Ammonium ions also mimic the effects of salinity in induction of gdh-NAD;A1 expression. These results, confirmed in tobacco and grape (Vitis vinifera cv Sultanina) tissues, support the hypothesis that the salinity-generated ROS signal induces α-GDH subunit expression, and the anionic iso-GDHs assimilate ammonia, acting as antistress enzymes in ammonia detoxification and production of Glu for Pro synthesis.

The expression of totipotency in plant protoplasts is a complex developmental phenomenon and is affected by genetic and physiological factors. Polyamines (PAs) are known to be involved in a variety of growth and developmental processes in higher plants, as well as in adaptation to stresses. In this study, we present the homeostatic characteristics of the endogenous PA putrescine (Put), spermidine (Spd), and spermine (Spm) in totipotent (T) and non-totipotent (NT) tobacco protoplasts and in recalcitrant (R) grapevine protoplasts. T-tobacco protoplasts, with high division rates, have the highest level of endogenous PAs. In these protoplasts, the soluble-hydrolyzed fraction predominates and increases, and the insoluble-hydrolyzed fraction also increases, whereas soluble (S) PAs decrease rapidly during culture. The isolation process contributes to the increased Put levels, which are higher in freshly isolated NT-tobacco protoplasts than in T-protoplasts. During culture, total Put predominates over Spd and Spm, and the highest accumulation is found in T-protoplasts. Ornithine decarboxylase and arginase activities both increase in T-protoplasts, whereas arginine decarboxylase activity causes Put accumulation in NT-tobacco protoplasts. R-grapevine protoplasts show a different PA profile, mostly due to the lower PA content, the higher S-fraction, and the higher ratio of Spm to total PAs. The data suggest that the levels and metabolism of the intracellular PAs could be related to the expression of totipotency of plant protoplasts.

The present work focuses on the influence of calcium addition in gasification. The inorganic–organic element interaction as well as the detailed inorganic–inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic–inorganic reactions take place very late in the char conversion process. Comprehensive global equilibrium calculations predicted important characteristics of the inorganic ash residue. Equilibrium calculations predict the formation of liquid salt if sufficient amounts of Ca are added and according to experiments as well as calculations calcium binds silicon primarily as calcium silicates and less as potassium calcium silicates.

Expression of totipotency and regeneration potentiality of plant protoplasts is a complex developmental phenomenon. The isolation per se is a stress-inducing procedure, during which, among others, active oxygen species (AOS) are generated. Thereafter, protoplasts undergo cell wall reconstitution, cell elongation and re-enter the cell cycle. AOS are known to participate in cell wall cross-linking and recently hydroxyl radicals were proposed to participate in cell wall loosening. On the other hand, if the antioxidant genes and the overall AOS scavenging machinery is not induced, protoplasts may suffer from oxidative stress and peroxidation of membrane lipids. In an effort to identify potential factors contributing to recalcitrance of plant protoplasts, we present the available information, which correlates AOS and oxidative stress with cell wall reconstitution, dedifferentiation, cell cycle progression, and cell death. Reduced antioxidant machinery and altered redox homeostasis seem to affect the regenerating potential of plant protoplasts and inevitably the protoplast fate (re-entry into cell cycle or cell death).

We previously showed that during protoplast isolation, an oxidative burst occurred and the generation of active oxygen species was differentially mediated in tobacco (Nicotiana tabacum) and grapevine (Vitis vinifera), accompanied by significant quantitative differences (A.K. Papadakis, K.A. Roubelakis-Angelakis [1999] Plant Physiol 127: 197–205). We have now further tested if the expression of totipotency in protoplasts is related to the activity of cellular antioxidant machinery during protoplast culture. Totipotent (T) tobacco protoplasts had 2-fold lower contents of intracellular O2 .− and H2O2 and 7-fold lower levels of O2 .− and H2O2 in the culture medium, compared with non-totipotent (NT) tobacco protoplasts. Addition of alkaline dimethylsulfoxide, known to generate O2 .−, resulted in isolation of tobacco protoplasts with reduced viability and cell division potential during subsequent culture. Active oxygen species levels decreased in tobacco and grapevine protoplasts during culturing, although higher contents of O2 .− and H2O2 were still found in NT- compared with T-tobacco protoplasts, after 8 d in culture. In T-tobacco protoplasts, the reduced forms of ascorbate and glutathione predominated, whereas in NT-tobacco and grapevine protoplasts, the oxidized forms predominated. In addition, T-tobacco protoplasts exhibited severalfold lower lipid peroxidation than NT-tobacco and grapevine protoplasts. Furthermore, several antioxidant enzyme activities were increased in T-tobacco protoplasts. Superoxide dismutase activity increased in tobacco, but not in grapevine protoplasts during culturing due to the increased expression of cytoplasmic Cu/Zn-superoxide dismutase. The increase was only sustained in T-tobacco protoplasts for d 8. Together, these results suggest that suppressed expression of totipotency in protoplasts is correlated with reduced activity of the cellular antioxidant machinery.

Our previous results have shown that oxidative stress may reduce the regeneration potential of protoplasts, but only protoplasts that are able to supply extracellularly H2O2 can actually divide (C.I. Siminis, A.K. Kanellis, K.A. Roubelakis-Angelakis [1993] Physiol Plant 87: 263–270; C.I. Siminis, A.K. Kanellis, K.A. Roubelakis-Angelakis [1994] Plant Physiol 1105: 1375–1383; A. de Marco, K.A. Roubelakis-Angelakis [1996a] Plant Physiol 110: 137–145; A. de Marco, K.A. Roubelakis-Angelakis [1996b] J Plant Physiol 149: 109–114). In the present study we have attempted to break down the oxidative burst response into the individual active oxygen species (AOS) superoxide (O2 ·−) and H2O2, and into individual AOS-generating systems during the isolation of regenerating tobacco (Nicotiana tabacum L.) and non-regenerating grape (Vitis vinifera L.) mesophyll protoplasts. Wounding leaf tissue or applying purified cellulase did not elicit AOS production. However, the application of non-purified cellulase during maceration induced a burst of O2 ·− and H2O2accumulation in tobacco leaf, while in grape significantly lower levels of both AOS accumulated. AOS were also generated when protoplasts isolated with purified cellulase were treated with non-purified cellulase. The response was rapid: after 5 min, AOS began to accumulate in the culture medium, with significant quantitative differences between the two species. In tobacco protoplasts and plasma membrane vesicles, two different AOS synthase activities were revealed, one that showed specificity to NADPH and sensitivity to diphenyleneiodonium (DPI) and was responsible for O2 ·−production, and a second NAD(P)H activity that was sensitive to KCN and NaN3, contributing to the production of both AOS. The first activity probably corresponds to a mammalian-like NADPH oxidase and the second to a NAD(P)H oxidase-peroxidase. In grape, only one AOS-generating activity was detected, which corresponded to a NAD(P)H oxidase-peroxidase responsible for the generation of both AOS.

Coronary artery disease (CAD) is one of the most common manifestations of atherosclerosis. Inflammation is considered one of the major processes that contribute to atherogenesis. Inflammation plays an important role not only on the initiation and progression of atherosclerosis but also on plaque rupture, an event that leads to acute vascular events. Various biomarkers express different pathways and pathophysiologic mechanisms of cardiovascular disease, and inflammatory biomarkers express different parts of the atherogenic process, regarding the initiation and progression of atherosclerosis or the destabilization of the atherosclerotic plaque. Therefore, inflammatory biomarkers may prove to be useful in the detection, staging, and prognosis of patients with CAD. Furthermore, the fact that inflammatory processes are essential steps in the course of the disease offers future therapeutic targets for the interruption of the atherogenic process or for the management of acute events. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Background/aim: The spontaneous preterm birth (SPB) rates in a group of HBeAg-negative chronic HBV infected pregnant women without several known risk factors for preterm delivery as well as the mother to infant HBV transmission rates was evaluated. Moreover the role of maternal data during perinatal period as well as the role of HBsAg and/or HBV-DNA presence in cord blood in respect to preterm labour and vertical transmission of the infection was examined. Methods: 138 consecutive chronic HBV infected pregnant women were haematologically, serologically and virologically evaluated during the perinatal period. 102 women were finally evaluated and fifteen of them (14.7%) exhibited SPB. Overall, 44 infants who had completed the proposed vaccination schedule were evaluated at month 12 of their life. Results: A significant association between SPB and HBV-DNA presence in cord blood was observed (p = 0.007). HBV-DNA positivity in cord blood was significantly associated with maternal HBV-DNA levels (p = 0.002). The relative risk of HBV-DNA presence in cord blood was 6.43 times higher among women with serum HBV-DNA ≥ 10.000 copies/ml and lymphocyte count < 1500 compared to those with all the other combinations of both parameters (p = 0.001). All infants evaluated at month 12 were HBsAg-negative and exhibited undetectable HBV-DNA levels. Conclusion: The presence of HBV-DNA in cord blood is significantly associated with SPB in chronic HBV infected pregnant women. Maternal or cord blood viremia does not pose an additional risk factor for vertical transmission of HBV infection, in passive-active immunoprotected infants from HBeAg-negative chronic HBV infected mothers. © 2010 European Federation of Internal Medicine.

Background. Ankylosing spondylitis is a rheumatic disease in which spinal and sacroiliac joints are mainly affected. There is a gradual bone formation in the spinal ligaments and ankylosis of the spinal diarthroses which lead to stiffness of the spine. The diffuse paraspinal ossification and inflammatory osteitis of advanced Ankylosing spondylitis creates a fused, brittle spine that is susceptible to fracture. The aim of this study is to present the surgical experience of spinal fractures occurring in patients suffering from ankylosing spondylitis and to highlight the difficulties that exist as far as both diagnosis and surgical management are concerned. Methods. Twenty patients suffering from ankylosing spondylitis were operated due to a spinal fracture. The fracture was located at the cervical spine in 7 cases, at the thoracic spine in 9, at the thoracolumbar junction in 3 and at the lumbar spine in one case. Neurological defects were revealed in 10 patients. In four of them, neurological signs were progressively developed after a time period of 4 to 15 days. The initial radiological study was negative for a spinal fracture in twelve patients. Every patient was assessed at the time of admission and daily until the day of surgery, then postoperatively upon discharge. Results. Combined anterior and posterior approaches were performed in three patients with only posterior approaches performed on the rest. Spinal fusion was seen in 100% of the cases. No intra-operative complications occurred. There was one case in which superficial wound inflammation occurred. Loosening of posterior screws without loss of stability appeared in two patients with cervical injuries. Frankel neurological classification was used in order to evaluate the neurological status of the patients. There was statistically significant improvement of Frankel neurological classification between the preoperative and postoperative evaluation. 35% of patients showed improvement due to the operation performed. Conclusion. The operative treatment of these injuries is useful and effective. It usually succeeds the improvement of the patients' neurological status. Taking into consideration the cardiovascular problems that these patients have, anterior and posterior stabilization aren't always possible. In these cases, posterior approach can be performed and give excellent results, while total operation time, blood loss and other possible complications are decreased. © 2009 Sapkas et al.

We report the case of an achondroplastic dwarf who presented with partial paraplegia due to cauda equina compression. The patient had marked thoracolumbar kyphosis and spinal stenosis at L2-L3. Although only posterior decompression is recommended in the literature for the treatment of achondroplastic patients presenting with neurological problems, a staged anterior and posterior decompression and stabilization was considered necessary for the treatment of this particular patient due to the presence of kyphosis. Satisfactory clinical results were achieved and sustained for six years following this complex operation. © 2008 Sapkas et al; licensee BioMed Central Ltd.

Background Digital ulcers (DUs) are a manifestation of the underlying vasculopathy in systemic sclerosis. They can cause serious complications, including infection and digital loss, and impact hand function and quality of life. Bosentan, an endothelin receptor antagonist, has previously been shown to reduce the occurrence of new DUs in systemic sclerosis. Objectives We report results of two randomised placebo-controlled trials (DUAL-1 and DUAL-2), designed to assess the potential benefit of the endothelin receptor antagonist macitentan on DUs in patients with systemic sclerosis and ongoing DU disease. Methods DUAL-1 and DUAL-2 were independent, multicenter, randomized, placebo-controlled, double-blind, parallel group trials that assessed the efficacy, safety, and tolerability of macitentan on DUs in patients with systemic sclerosis and at least 1 active DU. The target enrolment for each trial was 285 patients. Patients were randomised (1:1:1) to placebo, macitentan 3 mg or macitentan 10 mg once daily and were stratified according to the number of DUs at baseline (≤3 or >3). The primary outcome measure was the reduction of the cumulative number of new DUs at 16 weeks of treatment. Secondary assessments included hand functionality and DU burden. Safety and tolerability were also assessed. In each trial, the primary analysis was performed on all randomised patients. Results In DUAL-1, 289 patients were randomized to placebo (n=97), macitentan 3 mg (n=95), and macitentan 10 mg (n=97). In DUAL-2, 265 patients were randomized to placebo (n=89), macitentan 3 mg (n=88), and macitentan 10 mg (n=88). DUAL-2 was prematurely terminated based on the recommendation of the Independent Data Monitoring Committee, who determined that additional data were unlikely to result in a positive primary outcome measure; no unexpected safety findings were observed. The primary endpoint was not met in either trial (Table). There were no significant differences between active treatment and placebo for any of the secondary endpoints. In DUAL-1, 67.0%, 64.1%, and 63.0% of patients treated with placebo, macitentan 3 mg and macitentan 10 mg respectively had no new DUs by week 16, and 59.8%, 56.0%, and 54.8% of patients respectively in DUAL-2. Macitentan was well tolerated; adverse events (incidence >10%) that occurred more frequently with macitentan versus placebo (≥3% placebo-corrected difference) in DUAL-1 were headache and peripheral oedema, and in DUAL-2 were peripheral oedema, anaemia, nasopharyngitis, upper respiratory tract infection, skin ulcer, and diarrhoea. Conclusions In the DUAL-1 and DUAL-2 studies, treatment with macitentan did not reduce the cumulative number of new DUs over 16 weeks in patients with systemic sclerosis. These results do not support the use of macitentan for the treatment of DUs in this patient population. Acknowledgements The DUAL trials were funded by Actelion Pharmaceutical Ltd. The authors express their gratitude to all investigators and patients who participated in these trials. Disclosure of Interest C. Denton Grant/research support from: Actelion, Novartis and CSL Behring, Consultant for: Roche, Actelion, GSK, Inventiva and Boehringer Ingelheim, D. Khanna Grant/research support from: Actelion, Bayer, Biogen Idec, Bristol-Myers Squibb, EMD Serono, Gilead, InterMune, NIH, PH Association and the Scleroderma Foundation, Consultant for: Actelion, Bayer, Biogen Idec, Bristol-Myers Squibb, Cytori, EMD Serono, Genentech/Roche, GlaxoSmithKline, InterMune, Lycera, Sanofi-Aventis/Genzyme, T. Krieg Grant/research support from: Actelion, Consultant for: Actelion, F.-O. Le Brun Shareholder of: Actelion, Employee of: Actelion, P. Merkel Grant/research support from: Actelion, Bristol-Myers Squibb, Celgene, ChemoCentryx, Genentech/Roche and GlasoSmithKline, Consultant for: Actelion, Alexion, ChemoCentryx and Sanofi-Aventis/Genzyme, K. Papadakis Shareholder of: Actelion, Employee of: Actelion, J. Pope Grant/research support from: Actelion, Consultant for: Actelion, M. Matucci Cerinic Grant/research support from: Actelion, Speakers bureau: Actelion, GlasoSmithKline, Pfizer, AbbVie, MSD, Hospira and Bristol-Myers Squibb, D. Furst Grant/research support from: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Gilead, GlaxoSmithKlein, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Actelion, Amgen, Bristol-Myers Squibb, Cytori, Janssen, Gilead, GlaxoSmithKlein, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau: AbbVie, Actelion, UCB

Our previous results indicate that during protoplast isolation an oxidative burst occurs [A.K. Papadakis and KA Roubelakis-Angelakis (1999) Plant Physiol 127:197–205] and that suppression of totipotency is correlated with reduced antioxidant activity and low redox state [A.K. Papadakis et al. (2001b) Plant Physiol 126:434–444]. Polyamines are known to affect cell development and to act as antioxidants. Polyamines applied during isolation of tobacco (Nicotiana tabacum L.) protoplasts reduced the accumulation of O2·− but not that of H2O2. This antioxidant effect is probably due to the inhibition of microsomal membrane NADPH oxidase, which occurred in a concentration-dependent manner, with spermine exerting the highest inhibitory effect. However, during protoplast culture, polyamine oxidase activity increased severalfold in spermidine- and spermine-treated protoplasts, concomitant with H2O2 titers. A cell death program was executed in untreated protoplasts, as documented by membrane malfunction, induced DNase activity, DNA fragmentation and a positive TUNEL reaction. Protoplast cell death was prevented in protoplasts treated with putrescine, but not by treatment with spermidine or spermine, which rather had the opposite effect. The data presented suggest that PAs may be implicated in the expression of plant protoplast totipotency.

Objectives: To compare the psychophysical properties of the new Kodak InSight F-speed intraoral dental film with those for the E-speed Ektaspeed Plus film by means of the perceptibility curve (PC) test. Methods: A specially designed test object was used. The test object was made of aluminium and was 10 mm thick. It contained ten holes, contrast details, with the same diameter of 1.5 mm but with different depths. The depths ranged from 0.03 mm to 0.30 mm in steps of 0.03 mm. The holes were placed randomly within a square area with a total of 16 possible positions. Radiographs of the test object were obtained over the full exposure ranges of the two films. A Combex DX-907 dental X-ray unit was used operating at 10 mA and two tube potentials, 70 kVp and 90 kVp. The focus-to-object distance was 50 cm. Ten observers evaluated the radiographs under uniform artificial lighting using a view box and stated the number of perceptible representations of contrast details. In order to construct perceptibility curves, absolute values of the reciprocal of the minimum perceptible logarithmic exposure differences, 1/(DlogE)min, were plotted as functions of the logarithm of exposures, logE, registered by the tested films. Comparisons between the two films were made separately for the two tube potentials, 70 kVp and 90 kVp. Results: The results are presented graphically. PCs for the InSight film had higher peaks than those for the Ektaspeed Plus film. This indicates that the viewers were able to perceive smaller exposure differences in the former compared with the latter. PCs for the InSight film were shifted towards the left along the exposure axis relative to the PCs for the Ektaspeed Plus film indicating that the former film is more sensitive than the latter. The integrals of the PCs for InSight film were larger than those for Ektaspeed film indicating superior psychophysical properties of the InSight film. Conclusions: From the point of view of perception, the new InSight film has such psychophysical properties in comparison with Ektaspeed Plus film that it will be the more favourable of the two in clinical radiographic practice. © 2004 The British Institute of Radiology.

Hastein (1880) was probably the first to use the term protoplast, from the greek proto (πρώτο = first) and plastos (πλαστός = created), for plant cells lacking cell walls and to isolate protoplasts from cells of Vacuheria. In 1892, Klercker was the first to isolate protoplasts following plasmolysis of leaf tissue cells of Stratiotes aloides. Large scale isolation of protoplasts was started in the 60’s, when cell wall hydrolytic enzymes were employed (Cocking, 1961).

Cell suspension cultures were grown from explants of Atractylis gummifera in several culture media. The accumulated biomass differed in the various culture media. The presence of carboxyatractyloside and atractyloside was examined in relation to the different culture media, by means of HPLC. Carboxyatractyloside was identified in the biomass produced in only one of the culture media employed, while atractyloside was not present in detectable amounts in any of the biomasses.

Endometrial cancer is the most common female genital cancer and approximately 90% of the cases are diagnosed while they are still confined to the uterus. However, the natural history and treated course after the development of pulmonary metastasis (PM) have not been studied systematically in a large series of patients.Between 1962 and 1992, 100 patients (6%) with PM were identified by computerized search of the medical records from 1.665 patients admitted to our hospitals with the diagnosis of uterine cancer. The median age of the patients was 65.5 years (range: 42-87 yrs). The usual histologic types of the uterine neoplasms were 59 adenocarcinomas (59%), 21 sarcomas, and 14 adenosquamous carcinomas. Of the 83 patients with reported tumor grade, 11 had Grade 1 tumor, 12 Grade II, and 60 Grade III.Lung metastases were found at the time of diagnosis of the primary tumor in 22 patients. Hemoptysis was the first symptom of 3 of the 22; the majority had no respiratory symptoms. In the remaining 78 patients with PM appearing after primary therapy, the mean interval time between primary diagnosis and PM was 29.4 months, whereas between PM and death was 15.7 months. Of all patients with lung metastases, 75% did not survive 1 year; however 6% survived more than 5 years after diagnosis of metastatic disease. Patients with isolated PM had prolonged survival (36.1 mos, P=0.001), whether treated medically or with pulmonary resection. Progestin therapy was given to 39 patients, with complete response consisting of radiographic resolution of all disease in 6 patients (15%) and prolonged stabilization in an additional 5 (13%). The histologic grade of the primary tumor was predictive of clinical response to progestine therapy.Asymptomatic pulmonary metastases represent a common site of extra pelvic spread of disease. The majority of patients with PM (75%) do not survive 1 year. Low grade uterine tumors are more likely to respond to progestin therapy and do so for extended periods of time.

Background. Bcl-2 oncogene was identified as a transcript associated with the t (14;18) and exhibits the unique functional role of blocking apoptosis. Apoptosis as a remodelling mechanism has been reported to embryonic and adult kidney. The aim of this study was to investigate the expression of bcl-2 protein in normal and diseased renal tissue and to define any correlation with the type of renal injury. Materials and methods. Our material comprised of 10 normal adult kidneys, 31 renal allografts with acute (22) and chronic (9) rejection, and 70 renal biopsies with various types of primary (49) (31 proliferative and 18 non-proliferative) and secondary (21) glomerulonephritis. The immunohistochemical strept. ABC method was performed on paraffin sections for the detection of bcl-2 protein with a monoclonal antibody after microwave pretreatment. Results. Bcl-2 protein was detected in all the cases of normal and diseased renal tissue, showing an analogous expression. The antigen was expressed in a few parietal epithelial cells, in scattered proximal tubular epithelial cells, and in the majority of distal and collecting tubular epithelial cells, but not in the glomerular capillary tuft. No difference was found in bcl-2 expression between cases of proliferative and non-proliferative glomerulonephritis as a whole, or between primary and secondary glomerulonephritis. Bcl-2 expression in acute and chronic rejection demonstrated a similar cytoarchitectural expression to the one observed in normal kidneys and glomerulonephritis. Bcl-2 was detected in podocytes near intraglomerular fibrotic lesions and in epithelial cells of early adhesions and cellular crescents, wherever observed in cases of glomerulonephritis. However, bcl-2 expression in proximal tubular epithelial cells was significantly higher in cases of proliferative glomerulonephritis than in non-proliferative glomerulonephritis (P < 0.001), while bcl-2 expression in parietal epithelial cells in cases of chronic rejection was higher than in cases of acute rejection (P < 0.08). Conclusions. The absence of bcl-2 expression in normal and diseased glomeruli suggests and supports the reported notion that the mechanism of apoptosis may be available in the injured glomerulus. Moreover, bcl-2 expression in podocytes near intraglomerular fibrotic lesions and in epithelial cells of early adhesions and cellular crescents indicates the deregulation of apoptosis and its possible role in the progression of glomerular scarring.

ECG chest wall mapping with bicycle ergometry which can detect not only myocardial ischaemia but also individual coronary artery territories involved has been used to screen 100 consecutive patients presenting with claudication. Fifty-three had a positive history and/or evidence of ischaemic heart disease on a resting ECG. The test was positive in 38, negative in 38 and inconclusive in 24, the latter because of inadequate heart rate response. In 11 out of 38 (29%) with a positive test there was no history or evidence of myocardial ischaemia on a conventional resting ECG. ECG changes suggestive of three vessel coronary disease were found in three, single vessel coronary disease in 16 and two vessel disease in 19. Of the latter, eight had changes in the LAD/circumflex distribution, indicating left main stem or equivalent disease. These together with the three with triple vessel coronary disease constituted a subset of 11 (11%) high risk patients who merited coronary angiography with a view to confirming the presence of severe coronary disease.