Surface-Dominated Finite-Size Effects in Nanoconfined Superfluid Helium.

Superfluid ^{4}He (He II) is a widely studied model system for exploring finite-size effects in strongly confined geometries. Here, we study He II confined in millimeter-scale channels of 25 and 50 nm height at high pressures using a nanofluidic Helmholtz resonator. We find that the superfluid density is measurably suppressed in the confined geometry from the transition temperature down to 0.6 K. Importantly, this suppression can be accounted for by rotonlike thermal excitations with an energy gap of 5 K. We show that the surface-bound excitations lead to the previously unexplained lack of finite-size scaling of suppression of the superfluid density.

Observation of Bistable Turbulence in Quasi-Two-Dimensional Superflow.

Turbulent flow restricted to two dimensions can spontaneously develop order on large scales, defying entropy expectations and in sharp contrast with turbulence in three dimensions where nonlinear turbulent processes act to destroy large-scale order. In this work we report the observation of unusual turbulent behavior in steady-state flow of superfluid ^{4}He-a liquid with vanishing viscosity and discrete vorticity-in a nearly two-dimensional channel. Surprisingly, for a range of experimental parameters, turbulence is observed to exist in two bistable states. This bistability can be well explained by the appearance of large-scale regions of flow of opposite vorticity.

Presence of varicella zoster virus in zosteriform leukaemia cutis.

Leukaemia cutis is a relatively rare manifestation in chronic lymphocytic leukaemia, characterized by a diverse morphology of skin lesions. We report two patients who developed zosteriform skin symptoms; however, the histological analysis revealed leukaemia infiltration as the cause of their symptoms. Contrary to previous reports, varicella zoster virus DNA was detectable in the lesions. These findings suggest that varicella zoster virus plays an active role in the development of zosteriform leukaemia cutis.

The management and genetic background of pityriasis rubra pilaris: a single-centre experience.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory dermatosis with multifactorial aetiology. It is known that particular caspase recruitment domain family member 14 (CARD14) gene mutations are associated with familial PRP and certain forms of psoriasis. Additionally, few data are available about the role of CARD14 gene variants in sporadic PRP. The clinical picture is variable for the different types of PRP, therefore choosing the adequate treatment is often difficult, furthermore there are no specific guidelines for therapy. OBJECTIVE: Our aim was to survey the efficacy of the applied therapies and to screen the CARD14 gene variants in our PRP patients. METHODS: In this retrospective study, patients diagnosed with PRP between 2006 and 2016 at our clinic were involved. Besides the follow-up study of the treatments, the genetic analysis of CARD14 gene was performed. RESULTS: We analysed 19 patients, among whom 17 were diagnosed with type I, one with type III, and one with type V PRP. The majority of the patients were successfully treated with acitretin in combination with systemic corticosteroids, and the remaining patients were treated with other systemic therapies with diverse effects. The genetic screening of CARD14 gene revealed two previously described mutations (rs114688446, rs117918077) and six polymorphisms (rs28674001, rs2066964, rs34367357, rs11653893, rs11652075, rs2289541). Ten of 19 patients carried different CARD14 genetic variants either alone or in combination. CONCLUSION: Based on our experience, we propose that acitretin and an initial combination of short-term systemic corticosteroid therapy could be a successful treatment option for PRP. Although we identified several CARD14 variants in almost half of our cases, we did not find a correlation between the therapeutic response and the genetic background. Our data support the previous observation that CARD14 genetic variants are not specific to PRP, although they may indicate chronic inflammation.

Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy.

PURPOSE: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. METHODS: We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. RESULTS: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. CONCLUSIONS: Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.

Cuprizone Administration Alters the Iron Metabolism in the Mouse Model of Multiple Sclerosis.

Cuprizone (CZ) is a widely used copper chelating agent to develop non-autoimmune animal model of multiple sclerosis, characterized by demyelination of the corpus callosum (CC) and other brain regions. The exact mechanisms of CZ action are still arguable, but it seems that the only affected cells are the mature oligodendrocytes, possibly via metabolic disturbances caused by copper deficiency. During the pathogenesis of multiple sclerosis, high amount of deposited iron can be found throughout the demyelinated areas of the brain in the form of extracellular iron deposits and intracellularly accumulated iron in microglia. In the present study, we used the accepted experimental model of 0.2% CZ-containing diet with standard iron concentration to induce demyelination in the brain of C57BL/6 mice. Our aim was to examine the changes of iron homeostasis in the CC and as a part of the systemic iron regulation, in the liver. Our data showed that CZ treatment changed the iron metabolism of both tissues; however, it had more impact on the liver. Besides the alterations in the expressions of iron storage and import proteins, we detected reduced serum iron concentration and iron stores in the liver, together with elevated hepcidin levels and feasible disturbances in the Fe-S cluster biosynthesis. Our results revealed that the CZ-containing diet influences the systemic iron metabolism in mice, particularly the iron homeostasis of the liver. This inadequate systemic iron regulation may affect the iron homeostasis of the brain, eventually indicating a relationship among CZ treatment, iron metabolism, and neurodegeneration.

First Cryptosporidium outbreak in Hungary, linked to a treated recreational water venue in 2015.

In June 2015, an outbreak of cryptosporidiosis with 35 cases (23 probable and 12 laboratory-confirmed) occurred among 191 attendees of a residential rehabilitation holiday for paediatric organ transplant patients (n = 49) and their families at a hotel in Somogy county, Hungary. The overall attack rate was 18%. Most of the cases were transplanted children who experienced severe acute disease and required adjustment to their tacrolimus immunosuppression. A retrospective case-control study suggested an association between recreational water exposures and illness: cases were seven times more likely than controls to have swum in the children's pool (odds ratio 7.17; 95% confidence interval 2.9-17.2; P < 0.0001) and five times more likely to have used the jetted whirlpool (odds ratio 5.25; 95% confidence interval 2.1-13.1; P < 0.0001). This was the first outbreak of cryptosporidiosis in Hungary and it is especially unfortunate that it affected vulnerable children who experienced severe symptoms. Cryptosporidium presents specific infection control difficulties in treated recreational water venues; the link to a whirlpool is unusual and highlights the importance of the age-appropriate use of these facilities and reminding users not to immerse their heads or swallow the water. Cryptosporidiosis is more commonly linked to children' pools where improved bather hygiene and promoting exclusion of diarrhoea cases could help to avoid similar outbreaks.

Successful second hematopoietic cell transplantation in severe congenital neutropenia.

Allogeneic HCT is curative for SCN; however, a standard conditioning regimen or intensity has not been established. We describe a patient with SCN associated with c.1A>G (M1V) mutation in ELANE gene resulting in refractoriness to G-CSF, who received reduced-intensity HCT and developed secondary graft failure requiring a second myeloablative HCT. This case suggests that M1V mutation confers a poor G-CSF response and HCT using the best available donor is beneficial.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. RESULTS: Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. CONCLUSIONS: The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established.

Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. METHODS: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. RESULTS: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63, -0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores. CONCLUSIONS: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.

[Polyphenolic compounds analysis and antioxidant activity in fruits of Prunus spinosa L.] / Not available.

INTRODUCTION: Prunus spinosa L. (blackthorn, sloe) is a com- mon species in the wild flora of Europe. Marmalade, syrup, and alcoholic beverages have been prepared from fruits. In folk medicine they'are used due to the astringent effect. However there are few studies on these indigenous fruits. According to the literature they contain tannins, anthocyanins, sugars, vitamin C etc. METHODS: Our objective is to determine the antioxidant activity as related to their phenolic composition. For this purpose we prepared extracts using methanol, methanol-water (1: 1) and water. The antioxidant activity was determined by DPPH method and by photochemiluminescens (PCL) method. The total polyphenols, total anthocyanins and flavonoids were determined by colorimetric methods. Individual polyphenols were identified by a RP-HPLC-UVIVIS method. RESULTS: The antioxidant activity decreased in the extracts as follows: methanol > methanol-water > water (IC50= 1.33 mg/ml for DPPH; 11.94 µmol AAEIml for PCL > IC50 = 1.87 mg/ml for DPPH; 10.35 µmol AAElml for PCL > IC50 = 15.29 mg/ml for DPPH, 1.89 µmol AAElml for PCL) which is cor- related with the total polyphenol content (369 mg/100g > 244 mg1100g > 101 mg1100g) and total anthocyanin content (37.11 mg/100 g > 16.33 mg/100g > 7.76 mg/100g). The fla- vonoid content is similar in the three extracts (between 35.82 - 37.32 mg1100 g). The HPLC analysis shows high chloro- genic and neochlorogenic acid levels, followed by glycosides of quercetin. CONCLUSIONS: Our results demonstrated that blackthorn fruits are a rich source of phenolic compounds, with anti- oxidant activity, which are best extracted with methanol or methanol-water.

[Effect of culture to delusions: Introduction of the Truman Show delusion].

"People accepts the reality of the unfolded world" - says Peter Weir in his writing from 1998. The movie Truman Show demonstrates the life of a man, who - without knowing that - lived his life more than thirty years long at real time in a reality show. We could see the Truman Show delusion in international scientific literature in the past years, like a new, cultural formed shape of persecutory and grandiose delusions. The background of its maturation is given by the changed social norms and cultural effects, what let anybody to may get celebrity - without any vocation or hard work - within fifteen minutes and turning into the focus of millions. Patients, whom looking for the meaning of the feeling of "being changed" (depersonalisation, derealisation) constantly finds the answers in a kind of a directed reality, broadcasted by the television or other medias, where the people round them are playing pre-written roles. Similar as the Capgras sympton - they are different compared what they sound to be, need to execute tasks to avoid the unknown threats or gaining rewards. The paper gives not only a short overview about this rare psychopathological symptom, but also introduces this through three case studies observed at the Department of Psychiatry and Psychotherapy, University of Pecs, Hungary.

Probing the interaction of Rh, Co and bimetallic Rh-Co nanoparticles with the CeO2 support: catalytic materials for alternative energy generation.

The interaction of CeO2-supported Rh, Co and bimetallic Rh-Co nanoparticles, which are active catalysts in hydrogen production via steam reforming of ethanol, a process related to renewable energy generation, was studied by X-ray diffraction (XRD), high resolution electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and low energy ion scattering (LEIS). Furthermore, diffuse reflectance infrared spectroscopy (DRIFTS) of adsorbed CO as a probe molecule was used to characterize the morphology of metal particles. At small loadings (0.1%), Rh is in a much dispersed state on ceria, while at higher contents (1-5%), Rh forms 2-8 nm particles. Between 473-673 K pronounced oxygen transfer from ceria to Rh is observed and at 773 K significant agglomeration of Rh occurs. On reduced ceria, XPS indicates a possible electron transfer from Rh to ceria. The formation of smaller ceria crystallites upon loading with Co was concluded from XRD and HRTEM; for 10% Co, the CeO2 particle size decreased from 27.6 to 10.7 nm. A strong dissolution of Co into ceria and a certain extent of encapsulation by ceria were deduced by XRD, XPS and LEIS. In the bimetallic system, the presence of Rh enhances the reduction of cobalt and ceria. During thermal treatments, reoxidation of Co occurs, and Rh agglomeration as well as oxygen migration from ceria to Rh are hindered in the presence of cobalt.

Generation of transgene-free mouse induced pluripotent stem cells using an excisable lentiviral system.

One goal of research using induced pluripotent stem cell (iPSC) is to generate patient-specific cells which can be used to obtain multiple types of differentiated cells as disease models. Minimally or non-integrating methods to deliver the reprogramming genes are considered to be the best but they may be inefficient. Lentiviral delivery is currently among the most efficient methods but it integrates transgenes into the genome, which may affect the behavior of the iPSC if integration occurs into an important locus. Here we designed a polycistronic lentiviral construct containing four pluripotency genes with an EGFP selection marker. The cassette was excisable with the Cre-loxP system making possible the removal of the integrated transgenes from the genome. Mouse embryonic fibroblasts were reprogrammed using this viral system, rapidly resulting in large number of iPSC colonies. Based on the lowest EGFP expression level, one parental line was chosen for excision. Introduction of the Cre recombinase resulted in transgene-free iPSC subclones. The effect of the transgenes was assessed by comparing the parental iPSC with two of its transgene-free subclones. Both excised and non-excised iPSCs expressed standard pluripotency markers. The subclones obtained after Cre recombination were capable of differentiation in vitro, in contrast to the parental, non-excised cells and formed germ-line competent chimeras in vivo.