Staphylococcus aureus Serine protease-like protein A (SplA) induces IL-8 by keratinocytes and synergizes with IL-17A.

BACKGROUND: Serine protease-like (Spl) proteins produced by Staphylococcus (S.) aureus have been associated with allergic inflammation. However, effects of Spls on the epidermal immune response have not been investigated. OBJECTIVES: To assess the epidermal immune response to SplA, SplD and SplE dependent on differentiation of keratinocytes and a Th2 or Th17 cytokine milieu. METHODS: Human keratinocytes of healthy controls and a STAT3-hyper-IgE syndrome (STAT3-HIES) patient were cultured in different calcium concentrations in the presence of Spls and Th2 or Th17 cytokines. Keratinocyte-specific IL-8 production and concomitant migration of neutrophils were assessed. RESULTS: SplE and more significantly SplA, induced IL-8 in keratinocytes. Suprabasal-like keratinocytes showed a higher Spl-mediated IL-8 production and neutrophil migration compared to basal-like keratinocytes. Th17 cytokines amplified Spl-mediated IL-8 production, which correlated with neutrophil recruitment. Neutrophil recruitment by keratinocytes of the STAT3-HIES patient was similar to healthy control cells. CONCLUSION: S. aureus-specific Spl proteases synergized with IL-17A on human keratinocytes with respect to IL-8 release and neutrophil migration, highlighting the importance of keratinocytes and Th17 immunity in barrier function.

[Systemic treatment of moderate/severe hidradenitis suppurativa]. / Systemische Therapie der mittelschweren/schweren Hidradenitis suppurativa.

Systemic treatment together with radical surgical excision is the most important treatment option for all severity grades of hidradenitis suppurativa. Tetracycline in mild-to-moderate forms and clindamycin in combination with rifampicin in moderate-to-severe forms are guideline-compliant first-line therapy with a good clinical response. Other antibiotics such as ertepenem or multiple combinations are recommended as last-line therapy due to a lack of data. Success rate with dapsone and retinoids, on the other hand, are insufficient-only acitretin can be recommended on the basis of the available studies, but with limited success. With the TNF-alpha blocker adalimumab, an effective and safe long-term therapy is available-further biologics are in clinical trials and could significantly expand the treatment portfolio in the future.

Ensemble-Induced Strong Light-Matter Coupling of a Single Quantum Emitter.

We discuss a technique to strongly couple a single target quantum emitter to a cavity mode, which is enabled by virtual excitations of a nearby mesoscopic ensemble of emitters. A collective coupling of the latter to both the cavity and the target emitter induces strong photon nonlinearities in addition to polariton formation, in contrast to common schemes for ensemble strong coupling. We demonstrate that strong coupling at the level of a single emitter can be engineered via coherent and dissipative dipolar interactions with the ensemble, and provide realistic parameters for a possible implementation with SiV^{-} defects in diamond. Our scheme can find applications, amongst others, in quantum information processing or in the field of cavity-assisted quantum chemistry.

[Perioperative antibiotic prophylaxis in dermatosurgery-2019 status quo]. / Perioperative Antibiose in der Dermatochirurgie ­ Stand 2019.

Perioperative antibiotic prophylaxis (PAP) is determined as a short-term, in general single-shot administration of an antibiotic prior to a surgical intervention. The main goal of PAP is to reduce postoperative surgical site infections. In addition, PAP is administered to avoid development of bacterial endocarditis in patients who are at high risk. Regarding the increasing prescription of antibiotics by dermatologists and the rising emergence of resistant bacterial strains, a rational use of PAP in dermatosurgery has to be demanded. Thus, identification of risk factors being determined either by the patient, the type of surgery or the location will help to identify those patients requiring PAP. Moreover, utilizing established criteria will avoid the unnecessary administration of PAP-which only creates a false sense of safety.

[The role of the innate immune system in atopic dermatitis]. / Zur Rolle des angeborenen Immunsystems bei atopischer Dermatitis.

The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

[Knowledge about HBV, prevention behaviour and treatment adherence of patients with chronic hepatitis B in a large referral centre in Germany]. / Wissensstand, Präventionsverhalten und Therapieadhärenz von Patienten mit chronischer Hepatitis B in einem großen tertiären Zentrum in Deutschland.

BACKGROUND: The incidence of chronic hepatitis B in Germany is approximately 0.5 %. Data regarding knowledge about HBV, prevention behaviour and treatment adherence in patients with chronic HBV are scarce. METHODS: In this prospective study 201 consecutive patients with CHB infection were studied from a large urban academic outpatient clinic at the University Medical Centre in Hamburg. Patients were interviewed with a questionnaire that contained 47 questions covering social demographic dates, knowledge about HBV, treatment adherence and prevention. The success rate of interviews was 100 % with free translation service offered. RESULTS: 20.4 % of the CHB patients were born in Germany, but the majority of the patients were immigrants (80.6 %). 51 % of the patients had a good, 34 % a moderate and 15 % a poor knowledge about HBV. 89 % of the patients knew that HBV can be transmitted through blood contacts, but 34 % believed that inadequate hygienic conditions and 24 % that food products may transmit the virus. 96 % of the patients had knowledge about the existence of an HBV vaccine. Furthermore, 82 % considered a vaccination of all persons in the household important. Despite the knowledge of the existence and importance of a vaccine, only 61,7 % of the 300 affected children/siblings of HBV-positive family members were vaccinated. However, the child vaccination rate was significantly higher among patients with knowledge about the protective effect of the vaccine (p < 0.001), the free of charge vaccination program for children up to 18 years (p < 0.001) and higher school education (p < 0.001). Migrants with poor German language skills had lower knowledge scores (p < 0.001) and showed lower vaccination rates (p = 0.016) compared to immigrants with good German language skills. 43 % of all patients were treated with nucleot(s)ide analogues with a median treatment duration of 2 - 5 years. 65 % of these patients declared to never have missed a dose and 27 % missed less than one dose per month. 90 % of the patients tolerated the antiviral drugs very well and between patients with or without side effects there was no significant difference in quality of life. CONCLUSION: Chronic hepatitis B in Germany is characterised by awareness problems and language barriers. More attention is needed for HBV-infected immigrants in the form of multilingual information about CHB and awareness campaigns.

Basal serum tryptase as risk assessment for severe Hymenoptera sting reactions in elderly.

BACKGROUND: Epidemiologic studies suggest that elderly people are more prone to develop severe anaphylactic reactions. However, the exact cause for this phenomenon remains unclear. AIMS OF THE STUDY: To study the role of the serum tryptase as a diagnostic parameter for individual risk evaluation and its impact on the severity of allergic reactions in elderly people. METHODS: Two hundred and seventy-four consecutive patients visiting the Department of Dermatology, Tübingen, Germany, who were diagnosed with honeybee or wasp venom allergy, were included in the study. RESULTS: Sting reaction severity increased with increased age and tryptase levels (P = 0.001 and P = 0.0003, respectively). Furthermore, we find not only a general increment in tryptase levels in elderly people (P = 0.0001) but also a continuous increase in tryptase concentrations even below the cut-off (11.4 microg/l) with increasing age (P = 0.0026). CONCLUSIONS: Our data confirm serum tryptase as a risk factor for severe anaphylactic reaction to hymenoptera stings. Furthermore, we give first evidence that basal serum tryptase levels increase continuously with age and being an indicator for either increased mast cell load or reactivity this can at least partly be responsible for the observed aggravated allergic reactions in elderly people. As those patients are at increased risk for life-threatening anaphylactic reactions, it should be considered to adjust VIT especially in elderly patients with elevated tryptase levels as recommended for patients with mastocytosis by increasing venom doses during VIT and by considering its life-long continuation.

Optically tunable spontaneous Raman fluorescence from a single self-assembled InGaAs quantum dot.

We report the observation of all-optically tunable Raman fluorescence from a single quantum dot. The Raman photons are produced in an optically driven Lambda system defined by subjecting the single electron charged quantum dot to a magnetic field in Voigt geometry. Detuning the driving laser from resonance, we tune the frequency of the Raman photons by about 2.5 GHz. The number of scattered photons and the linewidth of the Raman photons are investigated as a function of detuning. The study presented here could form the basis of a new technique for investigating spin-bath interactions in the solid state.

[Outside-in. Probiotic topical agents]. / Outside-in. Probiotische Externa.

In dermatology probiotic microorganisms have primarily been used orally for the prophylaxis and treatment of atopic disorders. In contrast to the successes achieved for gastrointestinal disorders, positive effects for atopic dermatitis only have been found in a few studies. New insights could now fundamentally change the impact of probiotics on dermatology. Probiotics are - like microflora of the skin - non-pathogenic microbes, which do not induce inflammatory responses in the skin. Common pathways for probiotics, non-pathogenic microbes, and microflora are characterized, in order to facilitate their more effective therapeutic use. These microbes display a majority of their effects directly at the site of application and thereby induce natural defense mechanisms. However, promotion of immunological tolerance is just as important in producing positive effects. Tolerance of the resident flora on surface organs developed during evolution and the mechanisms of action are multifaceted. Therefore, the topical application of probiotics and non-pathogenic microbes for prophylaxis and therapy of overwhelming cutaneous pro-inflammatory immune reactions is very promising. Results of recent clinical trials already have demonstrated the efficacy of this new therapeutic concept.

Effects of nonpathogenic gram-negative bacterium Vitreoscilla filiformis lysate on atopic dermatitis: a prospective, randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Atopic dermatitis (AD) is associated with elevated IgE levels and Th2 responses. The oral administration of nonpathogenic bacteria such as probiotics may improve the course of atopic diseases. It is believed that nonpathogenic bacteria prevent the development of allergic diseases by modulating intestinal immune responses. However, the effects of oral probiotics on AD could not be reproduced in all studies and the direct immunomodulation of the skin-associated immune response by nonpathogenic bacteria has not yet been investigated. OBJECTIVES: We performed a prospective, double-blind, placebo-controlled clinical study with a cream containing a 5% lysate of the nonpathogenic bacteria Vitreoscilla filiformis. PATIENTS AND METHODS: Seventy-five volunteers with AD (6-70 years of age) were randomized to receive either V. filiformis cream 5% or vehicle cream daily for 30 days. Efficacy was evaluated by the SCORe of Atopic Dermatitis (SCORAD), transepidermal water loss (TEWL), assessment of microflora, and the patient's assessment of itch and loss of sleep. RESULTS: Compared with placebo, V. filiformis lysate significantly decreased SCORAD levels (P=0.0044) and pruritus (P=0.0171). Active cream significantly decreased loss of sleep from day 0 to day 29 (P=0.0074). Qualitative and quantitative assessment of cutaneous microbial colonization revealed that V. filiformis lysate reduced Staphylococcus aureus colonization of the skin. The skin barrier as determined by TEWL also improved significantly with the cream alone. CONCLUSIONS: V. filiformis lysate significantly improved AD. This may be in part due to reduction of S. aureus, but seems to relate in most parts to a direct immunomodulatory effect on skin-associated immune responses.

Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study.

BACKGROUND: Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option. OBJECTIVES: To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP. METHODS: Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts. RESULTS: Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1). CONCLUSIONS: Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.

Strong dissipation inhibits losses and induces correlations in cold molecular gases.

Atomic quantum gases in the strong-correlation regime offer unique possibilities to explore a variety of many-body quantum phenomena. Reaching this regime has usually required both strong elastic and weak inelastic interactions because the latter produce losses. We show that strong inelastic collisions can actually inhibit particle losses and drive a system into a strongly correlated regime. Studying the dynamics of ultracold molecules in an optical lattice confined to one dimension, we show that the particle loss rate is reduced by a factor of 10. Adding a lattice along the one dimension increases the reduction to a factor of 2000. Our results open the possibility to observe exotic quantum many-body phenomena with systems that suffer from strong inelastic collisions.

Neuropharmacological mechanisms underlying the neuroprotective effects of methylphenidate.

Methylphenidate is a psychostimulant that inhibits the neuronal dopamine transporter. In addition, methylphenidate has the intriguing ability to provide neuroprotection from the neurotoxic effects of methamphetamine and perhaps also Parkinson's disease; both of which may likely involve the abnormal accumulation of cytoplasmic dopamine inside dopaminergic neurons and the resulting formation of dopamine-associated reactive oxygen species. As delineated in this review, the neuroprotective effects of methylphenidate are due, at least in part, to its ability to attenuate or prevent this abnormal cytoplasmic dopamine accumulation through several possible neuropharmacological mechanisms. These may include 1) direct interactions between methylphenidate and the neuronal dopamine transporter which may attenuate or prevent the entry of methamphetamine into dopaminergic neurons and may also decrease the synthesis of cytoplasmic dopamine through a D2 receptor-mediated signal cascade process, and 2) indirect effects upon the functioning of the vesicular monoamine transporter-2 which may increase vesicular dopamine sequestration through both vesicle trafficking and the kinetic upregulation of the vesicular monoamine transporter-2 protein. Understanding these neuropharmacological mechanisms of methylphenidate neuroprotection may provide important insights into the physiologic regulation of dopaminergic systems as well as the pathophysiology of a variety of disorders involving abnormal dopamine disposition ranging from substance abuse to neurodegenerative diseases such as Parkinson's disease.

Atom-molecule Rabi oscillations in a Mott insulator.

We observe large-amplitude Rabi oscillations between an atomic and a molecular state near a Feshbach resonance. The experiment uses 87Rb in an optical lattice and a Feshbach resonance near 414 G. The frequency and amplitude of the oscillations depend on the magnetic field in a way that is well described by a two-level model. The observed density dependence of the oscillation frequency agrees with theoretical expectations. We confirmed that the state produced after a half-cycle contains exactly one molecule at each lattice site. In addition, we show that, for energies in a gap of the lattice band structure, the molecules cannot dissociate.

Animal models for the study of HBV replication and its variants.

Enormous progresses in hepatitis B virus research have been made through the identification of avian and mammalian HBV related viruses, which offer ample opportunities for studies in naturally occurring hosts. However, none of these natural hosts belongs to the commonly used laboratory animals, and the development of various mouse strains carrying HBV transgenes offered unique opportunities to investigate some mechanisms of viral pathogenesis. Furthermore, the need to perform infection studies in a system harbouring HBV-permissive hepatocytes has lately led researchers to create new challenging human mouse chimera models of HBV infection. In this review, we will overview the type of animal models currently available in hepadnavirus research.

Feshbach resonances in rubidium 87: precision measurement and analysis.

More than 40 Feshbach resonances in rubidium 87 are observed in the magnetic-field range between 0.5 and 1260 G for various spin mixtures in the lower hyperfine ground state. The Feshbach resonances are observed by monitoring the atom loss, and their positions are determined with an accuracy of 30 mG. In a detailed analysis, the resonances are identified and an improved set of model parameters for the rubidium interatomic potential is deduced. The elastic width of the broadest resonance at 1007 G is predicted to be significantly larger than the magnetic-field resolution of the apparatus. This demonstrates the potential for applications based on tuning the scattering length.

Tannins in Puccinellia arctica: possible deterrents to herbivory by Canada geese.

Urban populations of Canada geese, Branta canadensis, pose a nuisance problem throughout most of the eastern United States and in other parts of the United States and Canada. Puccinellia arctica is a species of arctic grass that is unpalatable to Canada geese on the North Slope of Alaska and may prove to be an effective long-term and nonlethal means of controlling the growing populations of urban Canada geese. A comparative study of the secondary metabolites of both P. arctica and Puccinellia langeana and Poa pratensis, two palatable grass species that Canada geese generally consume, revealed no significant differences. However, ellagitannin levels were higher in P. arctica than in the palatable grass species and may be contributing to its unpalatability to Canada geese. These results support the potential to use P. arctica in public areas to control geese intrusions.

Validity of self-reported alcohol consumption in nondependent drinkers with unintentional injuries.

BACKGROUND: Self-report has become an anchor for alcohol assessment in the acute and primary care populations. The purpose of the study was to determine the validity of self-reported alcohol consumption after unintentional injuries in hospitalized, nondependent drinkers. METHODS: Non-alcohol-dependent subjects 18 years of age and older with unintentional injuries (n = 209) were enrolled in the study and were interviewed if they had either an admitting blood alcohol concentration (BAC) > or = 10 mg/dl (0.01 g/dl) or a positive screen for a history of problem drinking. The self-reported number of standard drinks, time that drinking commenced, sex, and weight were used to calculate estimated blood alcohol concentration (EBAC), which was then compared to the admission BAC. RESULTS: We had data to calculate the EBAC on 141 of the 209 subjects. Seven men and no women with positive (> or = 10 mg/dl) BAC denied drinking. Of the 134 subjects for whom we had data to calculate EBAC and who acknowledged drinking, mean BAC was 147.06 mg/dl and mean EBAC was 68.66 mg/dl. For women (n = 30), mean BAC was 149.53 mg/dl and mean EBAC was 114.67 mg/dl; for men (n = 104), mean BAC was 146.35 mg/dl and mean EBAC was 55.38 mg/dl. The Spearman's p between laboratory BAC and EBAC was 0.461 (p < 0.001) for all subjects (n = 134), 0.275 (NS) for women (n = 30), and 0.532 (p < 0.001) for men (n = 104). For women and men separately, multiple regression analyses were performed to predict BAC by using weight and reported number of drinks. For women, weight and number of drinks accounted for 3% of the variance in laboratory BAC [r = 0.181, F(2,47) = 0.797,p = NS]. In contrast, for men these same predictors accounted for 34% of the variance [r = 0.585, F(2,135) = 35.203,p < 0.001). CONCLUSIONS: Most nondependent patients with unintentional injury acknowledged drinking before injury. After injury, women and men have different patterns of reporting their drinking, with men more frequently underreporting but reporting more accurately and women more random in their self-reports.

The contribution of the different binding sites of the N-methyl-D-aspartate (NMDA) receptor to the expression of behavior.

The effects of competitive (CGP 37849 and CGP 39551) and non-competitive (dizocilpine) N-methyl-D-aspartate (NMDA) antagonists were tested in three animal models (catalepsy, sniffing, locomotion) and, in addition, the modulation of these effects by an agonist of the strychnine-insensitive glycine binding site was investigated. Both competitive and non-competitive NMDA antagonists reduced neuroleptic-induced catalepsy. Weak sniffing was induced by the competitive antagonist but strong sniffing by the non-competitive NMDA antagonist. Due to muscle relaxation the competitive antagonist reduced locomotion, in contrast to stimulation of locomotor activity induced by the non-competitive NMDA antagonist. The glycine agonist (D-cycloserine) potentiated the effects of the non-competitive but antagonized those of the competitive NMDA antagonist.