Dysbiosis of skin microbiota with increased fungal diversity is associated with severity of disease in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi remains poorly investigated. OBJECTIVES: We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization. METHODS: Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively. RESULTS: Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non-Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild-to-moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities. CONCLUSIONS: We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD.

[Anesthesia and intensive care ventilators: differences and usability in COVID-19 patients]. / Anästhesie- und Intensivbeatmungsgeräte: Unterschiede und Nutzbarkeit bei COVID-19-Patienten.

The current coronavirus disease 2019 (Covid-19) pandemia is a highly dynamic situation characterized by therapeutic and logistic uncertainties. Depending on the effectiveness of social distancing, a shortage of intensive care respirators must be expected. Concomitantly, many physicians and nursing staff are unaware of the capabilities of alternative types of ventilators, hence being unsure if they can be used in intensive care patients. Intensive care respirators were specifically developed for the use in patients with pathological lung mechanics. Nevertheless, modern anesthesia machines offer similar technical capabilities including a number of different modes. However, conceptual differences must be accounted for, requiring close monitoring and the presence of trained personnel. Modern transport ventilators are mainly for bridging purposes as they can only be used with 100% oxygen in contaminated surroundings. Unconventional methods, such as "ventilator-splitting", which have recently received increasing attention on social media, cannot be recommended. This review intends to provide an overview of the conceptual and technical differences of different types of mechanical ventilators.

Experimental observation of resonance manifold shrinking under zonal flow shear.

In two-dimensional turbulent systems the redistribution of energy can be described by quadratic nonlinear three-wave interactions, which are limited by resonance conditions. The set of coupling modes can be understood as resonant manifold. It has been predicted by theory that, in the presence of a shear flow, the resonant manifold in wave-number space shrinks in time favoring large-scale structures. The phenomenon of manifold shrinking in the presence of shear flows is studied the first time experimentally in drift wave turbulence at the stellarator TJ-K by bicoherence analysis. By estimating effective mode numbers characterizing the width of the manifold, it is demonstrated that increasing shear leads to a shrinking of the resonance manifold.

[Freiburg Cardiac Arrest Receiving Team (CART) : Interdisciplinary solution for the acute management of non-traumatic out-of-hospital cardiac arrest]. / Freiburger Cardiac Arrest Receiving Team (CART) : Konzept zur Strukturierung des Behandlungsablaufs nach nichttraumatischem außerklinischem Herz­Kreislauf-Stillstand in einem interdisziplinären Team.

Standard procedures and guidelines provide specific instructions for basic and advanced cardiac life support. Recommendations for the admission of patients from preclinical into clinical structures after successful cardiopulmonary resuscitation (CPR) are available, but only a few are detailed. In the presence of ST-elevation myocardial infarction after return of spontaneous circulation (ROSC), coronary angiography must be performed as soon as possible. However, acute management and consecutive diagnostic procedures after hospital admission are up to the doctor on duty, who can rely on standard internal hospital procedures at best. Despite the enormous progress and new findings in intensive care and emergency medicine, intra-hospital mortality, as well as long-term survival, after CPR remains low and depends on a wide variety of influencing factors. To optimize in-hospital acute care of successfully resuscitated patients, an interdisciplinary admission team, a so-called cardiac arrest receiving team (CART), has been implemented at the University Hospital of Freiburg, Germany. The aim of the CART is to provide primary care to resuscitated patients as quickly and in as standardized a manner as possible with predefined diagnostic and therapeutic pathways by a team with special expertise in the field of CPR and post-resuscitation management. Accordingly, clear criteria for procedures and the location of primary care (e.g. emergency room vs. cardiac catheter laboratory), the composition of the CART and concrete treatment measures were defined.

On the psychology and economics of antisocial personality.

How do fundamental concepts from economics, such as individuals' preferences and beliefs, relate to equally fundamental concepts from psychology, such as relatively stable personality traits? Can personality traits help us better understand economic behavior across strategic contexts? We identify an antisocial personality profile and examine the role of strategic context (the "situation"), personality traits (the "person"), and their interaction on beliefs and behaviors in trust games. Antisocial individuals exhibit a specific combination of beliefs and preferences that is difficult to reconcile with a rational choice approach that assumes that beliefs about others' behaviors are formed rationally and therefore, independently from preferences. Variations in antisocial personality are associated with effect sizes that are as large as strong variations in strategic context. Antisocial individuals have lower trust in others unless they know that they can punish them. They are also substantially less trustworthy, believe that others are like themselves, and respond to the possibility of being sanctioned more strongly, suggesting that they anticipate severe punishment if they betray their partner's trust. Antisocial individuals are not simply acting in their economic self-interest, because they harshly punish those who do not reciprocate their trust, although that reduces their economic payoff, and they do so nonimpulsively and in a very calculated manner. Antisocial individuals honor others' trust significantly less (if they cannot be punished) but also, harshly punish those who betray their trust. Overall, it seems that antisocial individuals have beliefs and behaviors based on a view of the world that assumes that most others are as antisocial as they themselves are.

In vitro efficacy of antifungal agents alone and in shampoo formulation against dandruff-associated Malassezia spp. and Staphylococcus spp.

OBJECTIVE: Dandruff is a complex skin condition characterized by unpleasant itching and flaking of the scalp. It is primarily attributed to the over colonization of Malassezia yeasts such as Malassezia globosa and Malassezia restricta. Some studies also suggest the involvement of staphylococci bacteria in dandruff disease pathogenesis. We aimed to access the effectiveness of anti-dandruff treatments by determining the efficacy of the active antifungal agents alone or in commercial shampoo formulations against Malassezia and Staphylococcus. METHODS: The minimum inhibitory concentrations of three anti-dandruff shampoo antifungals (zinc pyrithione, ketoconazole and ciclopirox) and the witch hazel extract, hamamelitannin were tested against commensal Malassezia and Staphylococcus species using broth microdilution methods. In experiments simulating shampoo exposure and washing conditions on the scalp, we also tested the ability of the above agents in shampoo formulation (Head and Shoulders® (H&S), Ketomed® , Sebiprox® , Erol Healthcare Hair Shampoo® respectively) along with a generic over-the-shelf shampoo to inhibit microbial growth. RESULTS: Ketomed® and H&S shampoo were the most effective treatments against Malassezia in in vitro assays and washing simulation experiments. Erol Healthcare Hair Shampoo® was less effective against Malassezia as it required a longer contact time to achieve growth inhibition for some species. Sebiprox® showed variable efficacy in washing and contact time experiments whereas the generic over-the-shelf shampoo was the least effective in inhibiting Malassezia and Staphylococcus growth. CONCLUSION: From these findings, it is reasonable that patients with dandruff may benefit from applying specific antifungal shampoo although results may vary with microbial species, time of contact and shampoo formulation components.

OBJECTIFS: Les pellicules sont une affection cutanée complexe caractérisée par des démangeaisons et une desquamation du cuir chevelu. Elles sont principalement attribuées à une colonisation excessive par des levures du genre Malassezia telles que Malassezia globosa et Malassezia restricta. Certaines études suggèrent également que des bactéries comme les staphylocoques sont impliquées dans la pathogenèse des pellicules. Nous désirions évaluer l'efficacité des traitements antipelliculaires en déterminant l'efficacité des antifongiques actifs seuls ou dans des formulations commerciales de shampooing contre Malassezia et les bactéries du genre Staphylococcus. MÉTHODES: Les concentrations minimales inhibitrices de trois antifongiques présents dans des shampooings antipelliculaires (pyrithione de zinc, kétoconazole et ciclopirox) ainsi que l'hamamélan, extrait d'hamamélis, ont été évaluées contre des espèces commensales de Malassezia et Staphylococcus en utilisant des méthodes de microdilution en culture. Dans des expériences simulant l'exposition au shampooing et les conditions de lavage sur le cuir chevelu, nous avons également testé la capacité à inhiber la croissance microbienne des agents décrits ci-dessus dans la formulation de shampooings (Head and Shoulders (H&S), Ketomed, Sebiprox, Erol Healthcare Hair Shampoo, respectivement) avec un produit générique trouvé dans le commerce. RÉSULTATS: Les shampooings Ketomed et H&S ont été les traitements les plus efficaces contre Malassezia dans des essais in vitro et dans des expériences de simulation de lavage. Le shampooing Erol Healthcare était moins efficace contre Malassezia in vitro car nécessitant un temps de contact plus long pour obtenir une inhibition de la croissance de certaines espèces. Sebiprox a montré une efficacité variable dans les expériences de lavage et de temps de contact alors que le shampooing générique était le moins efficace pour inhiber la croissance de Malassezia et Staphylococcus. CONCLUSION: Ces résultats suggèrent que les patients avec des pellicules peuvent raisonnablement retirer un bénéfice de l'utilisation d'un shampooing antifongique spécifique bien que les résultats puissent varier selon les espèces microbiennes, la durée du contact et des composants entrant dans la formulation du shampooing.

[Emergency Medicine : What do we need?] / Strukturen der Akut- und Notfallmedizin : Was benötigen wir?

The timely medical treatment of the population in emergency situations is an enormous challenge for the healthcare system and is becoming increasingly more important. Due to this development clinical acute and emergency medicine has undergone enormous progress and is in the process of further professionalization. Various specialist societies and medical associations have published essential position papers in recent years and demanded fundamentally new healthcare structures and assignments. Additionally, emergency medical healthcare structures and centers have already been established on the initiative of individual emergency medical specialist disciplines. The future challenge is the nationwide establishment, grouping and integration of the structures and processes within definitive healthcare centers. The main objective of all involved must be the optimal care of emergency patients.

Distinct epitope structures of defensin-like proteins linked to proline-rich regions give rise to differences in their allergenic activity.

BACKGROUND: Art v 1, Amb a 4, and Par h 1 are allergenic defensin-polyproline-linked proteins present in mugwort, ragweed, and feverfew pollen, respectively. We aimed to investigate the physicochemical and immunological features underlying the different allergenic capacities of those allergens. METHODS: Recombinant defensin-polyproline-linked proteins were expressed in E. coli and physicochemically characterized in detail regarding identity, secondary structure, and aggregation status. Allergenic activity was assessed by mediator releases assay, serum IgE reactivity, and IgE inhibition ELISA using sera of patients from Austria, Canada, and Korea. Endolysosomal protein degradation and T-cell cross-reactivity were studied in vitro. RESULTS: Despite variations in the proline-rich region, similar secondary structure elements were observed in the defensin-like domains. Seventy-four percent and 52% of the Austrian and Canadian patients reacted to all three allergens, while Korean patients were almost exclusively sensitized to Art v 1. This was reflected by IgE inhibition assays demonstrating high cross-reactivity for Austrian, medium for Canadian, and low for Korean sera. In a subgroup of patients, IgE reactivity toward structurally altered Amb a 4 and Par h 1 was not changed suggesting involvement of linear epitopes. Immunologically relevant endolysosomal stability of the defensin-like domain was limited to Art v 1 and no T-cell cross-reactivity with Art v 125-36 was observed. CONCLUSIONS: Despite structural similarity, different IgE-binding profiles and proteolytic processing impacted the allergenic capacity of defensin-polyproline-linked molecules. Based on the fact that Amb a 4 demonstrated distinct IgE-binding epitopes, we suggest inclusion in molecule-based allergy diagnosis.

[Preclinical use of mild therapeutic hypothermia after cardiac arrest by the emergency services in Baden-Württemberg, Germany]. / Einsatz der präklinischen milden Hypothermie nach Herz-Kreislauf-Stillstand durch die Notarztstandorte Baden-Württembergs.

BACKGROUND: During the last decade target temperature management has become an integral part of postresuscitation care. Within recent years there was a strong debate about the optimal target temperature, which might have effects on the preclinical induction of hypothermia. The present investigation focuses on the use of mild therapeutic hypothermia by emergency services in the state of Baden-Württemberg (Germany) and compares it to results of a prior study in 2008. METHODS: Between April and August 2014 a questionnaire was sent to all senior emergency physicians of emergency services in Baden Württemberg. The survey period was April to August of 2014. Parts of the questionnaire were similar to a previous one in 2008, to ensure comparability to the former data; other parts were added to set new focuses. The data were analyzed in anonymized form. RESULTS: The response rate was 72.4% (97/134). Of the 97 sites which responded to the questionnaire significantly more use preclinical hypothermia, compared to 2008 (72.2% [70/97] vs. 41.7%); 62.9% (44/70) declare cooling resuscitated patients routinely (vs. 17.7% in 2008). Cold infusions (85.7%), icepacks (64.3%), passive cooling (37.1%), nasal cooling (2.9%) and cooling caps (1.4%) are used (multiple naming was possible). Sites that did not use mild therapeutic hypothermia stated the following reasons: lack of equipment, short transport time and missing data for the intervention. Four sites reported on complications with therapeutic hypothermia. CONCLUSION: The present investigation shows an increased use of preclinical cooling after cardiopulmonary resuscitation as compared to 2008. Therefore, recent discussions concerning the optimal target temperature in postresuscitation care did not result in a waiving of preclinical therapeutic strategies in Baden-Württemberg. The emergency services sites/locations estimated the complication rates of mild therapeutic hypothermia as very low. Lack of equipment seems to be the main reason to refuse the preclinical use of therapeutic hypothermia. In conclusion, preclinical mild therapeutic hypothermia has become an integral part in the standard care of resuscitated patients in Baden-Württemberg.

Fluorescent Labeling and 2-Photon Imaging of Mouse Tooth Pulp Nociceptors.

Retrograde fluorescent labeling of dental primary afferent neurons (DPANs) has been described in rats through crystalline fluorescent DiI, while in the mouse, this technique was achieved with only Fluoro-Gold, a neurotoxic fluorescent dye with membrane penetration characteristics superior to the carbocyanine dyes. We reevaluated this technique in the rat with the aim to transfer it to the mouse because comprehensive physiologic studies require access to the mouse as a model organism. Using conventional immunohistochemistry, we assessed in rats and mice the speed of axonal dye transport from the application site to the trigeminal ganglion, the numbers of stained DPANs, and the fluorescence intensity via 1) conventional crystalline DiI and 2) a novel DiI formulation with improved penetration properties and staining efficiency. A 3-dimensional reconstruction of an entire trigeminal ganglion with 2-photon laser scanning fluorescence microscopy permitted visualization of DPANs in all 3 divisions of the trigeminal nerve. We quantified DPANs in mice expressing the farnesylated enhanced green fluorescent protein (EGFPf) from the transient receptor potential cation channel subfamily M member 8 (TRPM8EGFPf/+) locus in the 3 branches. We also evaluated the viability of the labeled DPANs in dissociated trigeminal ganglion cultures using calcium microfluorometry, and we assessed the sensitivity to capsaicin, an agonist of the TRPV1 receptor. Reproducible DiI labeling of DPANs in the mouse is an important tool 1) to investigate the molecular and functional specialization of DPANs within the trigeminal nociceptive system and 2) to recognize exclusive molecular characteristics that differentiate nociception in the trigeminal system from that in the somatic system. A versatile tool to enhance our understanding of the molecular composition and characteristics of DPANs will be essential for the development of mechanism-based therapeutic approaches for dentine hypersensitivity and inflammatory tooth pain.

Amb a 1 isoforms: Unequal siblings with distinct immunological features.

BACKGROUND: Ragweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunological characteristics of Amb a 1 isoforms are not fully investigated. Here, we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms. METHODS: After purification, the isoforms were physicochemically characterized, tested for antibody binding and induction of human T-cell proliferative responses. Their immunological properties were further evaluated in vitro and in vivo in a mouse model. RESULTS: Amb a 1 isoforms exhibited distinct patterns of IgE binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients' T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity. CONCLUSION: The present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy for ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B- and T-cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy.

Collisional Scaling of the Energy Transfer in Drift-Wave Zonal Flow Turbulence.

The collisionality scaling of density and potential coupling together with zonal flow energy transfer and spectral power is investigated at the stellarator experiment TJ-K. With a poloidal probe array, consisting of 128 Langmuir probes, density and potential fluctuations are measured on four neighboring flux surfaces simultaneously over the complete poloidal circumference. By analyzing Reynolds stress and pseudo-Reynolds stress, it is found that, for increasing collisionality, the coupling between density and potential decreases which hinders the zonal flow drive. Also, as a consequence, the nonlinear energy transfer, as well as the zonal flow contribution to the complete turbulent spectrum, decreases the same way. This is in line with theoretical expectations and is a first experimental verification of the importance of collisionality for large-scale structure formation in magnetically confined toroidal plasmas.

A bird pollinator shows positive frequency dependence and constancy of species choice in natural plant communities.

Animal pollinators mediate reproduction of many plant species. Foraging theory suggests that animal pollinators exhibit preferences for common plant species in natural communities (positive frequency-dependent foraging) and temporary single-species specialization (flower constancy) during foraging bouts. Positive frequency dependence may favor common plant species; flower constancy may enhance conspecific pollen transfer particularly in rare plant species. Previous experimental studies suggest that avian pollinators are unlikely to exhibit these behaviors. We studied foraging behavior of Cape Sugarbirds (Promerops cafer), the main avian pollinator of many Protea species, using focal-plant and focal-bird sampling, assisted by high-resolution maps of the spatiotemporal distribution of Protea individuals and their flowering status. We found that Sugarbird's visitation preference increased with species' relative floral abundance, and that individual Sugarbirds tended to visit single species in sequence. Flower constancy during foraging bouts was significantly higher than expected from random plant-animal encounters at the scale of pollinator movements. Positive frequency dependence may favor the reproduction of abundant plant species while flower constancy may be particularly important for rare plant species. This first simultaneous study of both behaviors in a natural plant-pollinator system shows that bird pollinators exhibit both types of behavior and, in this way, possibly influence plant community structure.

[Current recommendations for basic/advanced life support : Addressing unanswered questions and future prospects]. / Aktuelle Empfehlungen zum Basic/Advanced Life Support : Adressierung offener Fragen und Zukunftsperspektiven.

The revised guidelines for cardiopulmonary resuscitation were implemented by the European Resuscitation Council (ERC) in October 2015. There were few changes concerning basic and advanced life support; however, some issues were clarified compared to the ERC recommendations from 2010. The present paper summarizes the procedures of basic and advanced life support according to the current guidelines and highlights the updates of 2015. Furthermore, the article depicts future prospects of cardiopulmonary resuscitation that may improve outcome of patients after cardiac arrest in the future.

Alterations in Body Fluid Balance During Fin Swimming in 29 °C Water in a Population of Special Forces Divers.

Highly trained "combat swimmers" encounter physiological difficulties when performing missions in warm water. The aim of this study was to assess the respective roles of immersion and physical activity in perturbing fluid balance of military divers on duty in warm water. 12 trained divers performed 2 dives each (2 h, 3 m depth) in fresh water at 29 °C. Divers either remained Static or swam continuously (Fin) during the dive. In the Fin condition, oxygen consumption and heart rate were 2-fold greater than during the Static dive. Core and skin temperatures were also higher (Fin: 38.5±0.4 °C and 36.2±0.3 °C and Static: 37.2±0.3 °C and 34.3±0.3 °C; respectively p=0.0002 and p=0.0003). During the Fin dive, the average mass loss was 989 g (39% urine loss, 41% sweating and 20% insensible water loss and blood sampling); Static divers lost 720 g (84% urine loss, 2% sweating and 14% insensible water loss and blood sampling) (p=0.003). In the Fin condition, a greater decrease in total body mass and greater sweating occurred, without effects on circulating renin and aldosterone concentrations; diuresis was reduced, and plasma volume decreased more than in the Static condition.

HLA class II peptide tetramers vs allergen-induced proliferation for identification of allergen-specific CD4 T cells.

BACKGROUND: Fluorescence-labeled MHC class II/peptide tetramer complexes are considered as optimal tools to characterize allergen-specific CD4(+) T cells, but this technique is restricted to frequently expressed HLA class II molecules and knowledge of immunodominant epitopes. In contrast, allergen-stimulated proliferation assessed by CFSE dilution is less sophisticated and widely applicable. The major mugwort allergen, Art v 1, contains only one single, immunodominant, HLA-DR1-restricted epitope (Art v 125-36 ). Thus, essentially all Art v 1-reactive cells should be identified by a HLA-DRB1*01:01/Art v 119-36 tetramer. METHODS: We compared specificity and sensitivity of tetramer(+) and allergen-induced proliferating (CFSE(lo) ) CD4(+) T cells by flow cytometry. RESULTS: The frequency of tetramer(+) CD4(+) T cells determined ex vivo in PBMC of mugwort-allergic individuals ranged from 0 to 0.029%. After 2-3 weeks of in vitro expansion, sufficient tetramer(+) T cells for phenotyping were detected in 83% of Art v 125-36 -reactive T-cell lines (TCL) from mugwort-allergic individuals, but not in TCL from healthy individuals. The tetramers defined bona fide Th2 cells. Notably, Art v 125-36 -reactive TCL depleted of tetramer(+) T cells still reacted to the peptide, and only 44% of Art v 125-36 -specific T-cell clones were detected by the tetramer. CFSE(lo) CD4(+) T cells contained only 0.3-10.7% of tetramer(+) T cells and very low proportions of Th2 cells. CONCLUSION: Allergen-specific T cells can be identified by HLA class II tetramers with high specificity, but unexpected low sensitivity. In contrast, allergen-stimulated CFSE(lo) CD4(+) T cells contain extremely high fractions of bystander cells. Therefore, for T-cell monitoring, either method should be interpreted with caution.