Comparison of Data-Dependent Acquisition, Data-Independent Acquisition, and Parallel Reaction Monitoring in Trapped Ion Mobility Spectrometry-Time-of-Flight Tandem Mass Spectrometry-Based Lipidomics.

The parallel accumulation-serial fragmentation (PASEF) approach based on trapped ion mobility spectrometry (TIMS) enables mobility-resolved fragmentation and a higher number of fragments in the same time period compared to conventional MS/MS experiments. Furthermore, the ion mobility dimension offers novel approaches for fragmentation. Using parallel reaction monitoring (prm), the ion mobility dimension allows a more accurate selection of precursor windows, while using data-independent aquisition (dia) spectral quality is improved through ion-mobility filtering. Owing to favorable implementation in proteomics, the transferability of these PASEF modes to lipidomics is of great interest, especially as a result of the high complexity of analytes with similar fragments. However, these novel PASEF modes have not yet been thoroughly evaluated for lipidomics applications. Therefore, data-dependent acquisition (dda)-, dia-, and prm-PASEF were compared using hydrophilic interaction liquid chromatography (HILIC) for phospholipid class separation in human plasma samples. Results show that all three PASEF modes are generally suitable for usage in lipidomics. Although dia-PASEF achieves a high sensitivity in generating MS/MS spectra, the fragment-to-precursor assignment for lipids with both, similar retention time as well as ion mobility, was difficult in HILIC-MS/MS. Therefore, dda-PASEF is the method of choice to investigate unknown samples. However, the best data quality was achieved by prm-PASEF, owing to the focus on fragmentation of specified targets. The high selectivity and sensitivity in generating MS/MS spectra of prm-PASEF could be a potential alternative for targeted lipidomics, e.g., in clinical applications.

Adjusted treatment COMPArisons between guSelkumab and uStekinumab for treatment of moderate-to-severe plaque psoriasis: the COMPASS analysis.

BACKGROUND: Guselkumab is an interleukin-23 inhibitor indicated for the treatment of moderate-to-severe plaque psoriasis in adults. Guselkumab has demonstrated additional benefit in patients with early inadequate response to ustekinumab. Long-term efficacy comparisons of guselkumab and ustekinumab are currently lacking among ustekinumab-naive patients. OBJECTIVES: To assess the relative efficacy of guselkumab and ustekinumab for maintenance therapy of moderate-to-severe plaque psoriasis, using individual patient data (IPD) from randomized controlled trials. METHODS: IPD for guselkumab from the VOYAGE 1 and 2 trials were pooled and compared with IPD for ustekinumab from the NAVIGATE trial. Multivariable logistic regression analyses compared guselkumab 100 mg and ustekinumab 45 mg or 90 mg for the achievement and maintenance of Psoriasis Area and Severity Index (PASI) 90, 75 and 100 responses up to 40 weeks. The regression models accounted for a range of clinically relevant covariates (e.g. age, sex, psoriasis duration). Relative efficacy was expressed using odds ratios (ORs) and predicted probability of treatment response associated with each intervention. RESULTS: Patients receiving guselkumab had significantly higher probabilities of achieving a PASI 90 response than patients receiving ustekinumab, at both week 16 [70·4% vs. 46·0%, OR 2·79, 95% confidence interval (CI) 2·22-3·45] and week 40 (74·2% vs. 54·5%, OR 2·40, 95% CI 1·89-3·13]. Guselkumab was also associated with a significantly increased likelihood of achieving both PASI 75 and PASI 100 responses at weeks 16 and 40, compared with ustekinumab. CONCLUSIONS: Adjusted analyses leveraging IPD demonstrate that guselkumab has a significantly higher probability of achieving and maintaining PASI treatment responses through week 40 than ustekinumab does.

[Selection of the optimal anesthesia regimen for cesarean section]. / Wahl des Anästhesieverfahrens zur Sectio caesarea.

Approximately one third of all children in Germany are delivered by cesarean section. Depending on the individual patient's condition and the situation, the anesthesiologist has to choose between a general or a regional anesthesia regimen. The decisive factor for the selection is the obstetric urgency (decision-delivery time) after ascertainment of the indications. Furthermore, the need for postoperative analgesia varies depending on the chosen anesthesia regimen.

[Airway management for lung separation in thoracic surgery : An update]. / Atemwegsmanagement zur Seitentrennung der Lunge bei thorakalen Eingriffen : Ein Update.

One of the main tasks in every anesthetist's routine clinical practice is securing the airway. This also includes techniques for lung isolation and one-lung ventilation in thoracic surgery and in intensive care medicine. The anesthesiologist has various methods available to achieve one-lung ventilation. This article presents the most commonly used methods for lung isolation. These include the double lumen tube, the bronchus blockers by Arndt and Cohen, the EZ blocker, the Uniblocker, the Univent tube and the VivaSight-DL™. The effects of the one-lung ventilation are not described in detail and for this the reader should refer to the appropriate literature. This article is intended to provide an overview of the various possibilities for lung separation, especially for physicians in continued medical education and also for physicians who rarely use these procedures.

Novel imidazolium salt--peptide conjugates and their antimicrobial activity.

Our study presents innovative research dealing with the synthesis and biological evaluation of conjugates out of antimicrobial peptides (AMPs) and imidazolium cations that are derived from ionic liquids. AMPs are considered as promising alternatives to common antibiotics due to their different activity mechanisms. Antibacterial effects have also been described for ionic liquids bearing imidazolium cations . Besides single coupling of carboxy-functionalized imidazolium cations to the peptide N-terminal we also developed conjugates bearing multiple copies of imidazolium cations. The combination of both compounds resulted in synergistic effects that were most pronounced when more imidazolium cations were attached to the peptides. In addition, antibacterial activity even in drug-resistant bacterial strains could be observed. Moreover, the novel compounds showed good selectivity only against bacterial cells, an observation that was further proven by lipid interaction studies using giant unilamellar vesicles.

Success and failure of dead-time models as applied to hybrid pixel detectors in high-flux applications.

The performance of a single-photon-counting hybrid pixel detector has been investigated at the Australian Synchrotron. Results are compared with the body of accepted analytical models previously validated with other detectors. Detector functionals are valuable for empirical calibration. It is shown that the matching of the detector dead-time with the temporal synchrotron source structure leads to substantial improvements in count rate and linearity of response. Standard implementations are linear up to ∼0.36 MHz pixel(-1); the optimized linearity in this configuration has an extended range up to ∼0.71 MHz pixel(-1); these are further correctable with a transfer function to ∼1.77 MHz pixel(-1). This new approach has wide application both in high-accuracy fundamental experiments and in standard crystallographic X-ray fluorescence and other X-ray measurements. The explicit use of data variance (rather than N(1/2) noise) and direct measures of goodness-of-fit (χ(r)(2)) are introduced, raising issues not encountered in previous literature for any detector, and suggesting that these inadequacies of models may apply to most detector types. Specifically, parametrization of models with non-physical values can lead to remarkable agreement for a range of count-rate, pulse-frequency and temporal structure. However, especially when the dead-time is near resonant with the temporal structure, limitations of these classical models become apparent. Further, a lack of agreement at extreme count rates was evident.

A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013.

Between October 2012 and May 2013, five cases of invasive meningococcal disease in young men who have sex with men (MSM) living in Berlin were notified to local health authorities in Germany. Three of the five cases died. All were caused by serogroup C variants with the finetype P1.5-1,10-8:F3-6. Awareness was increased through the use of community networks; an extension of the existing vaccination recommendation to all MSM is currently being considered.

Micrometre resolution of a charge integrating microstrip detector with single photon sensitivity.

A synchrotron beam has been used to test the spatial resolution of a single-photon-resolving integrating readout-chip coupled to a 320 µm-thick silicon strip sensor with a dedicated readout system. Charge interpolation methods have yielded a spatial resolution of σ(x) ≃ 1.8 µm for a 20 µm-pitch strip.

[Malignant melanoma of the skin: does screening for cancer influence the incidence and mortality?]. / Malignes Melanom der Haut: beeinflusst die Krebsfrüherkennung Inzidenz und Mortalität?

BACKGROUND: The increase in incidence of malignant melanoma, early diagnosis activities increasingly reaching ever larger population groups and mortality remaining at a constant level in trend comprise the background of the study. We aimed at answering the question whether the early diagnosis can have an influence on the increase in incidence and how one can one judge the effect on the reduction of the mortality. METHODOLOGY: The study is based on data from official tumour registries of the regions Saarland, Schleswig-Holstein, the administrative district Münster, the former GDR and the New Dfederal states (Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt, Thüringen), as well as that of Queensland (Australia). RESULTS: Parallel to the increasing incidence, there is also an increase in the number of melanomas detected at early stages. Hence, it is obvious to assume that this increase in incidence is due to a large extent to screening programmes. In a non-determinable number of cases, overdiagnostics could have contributed to the increase in incidence. In the period of observation mortality remained constant in the regions described in this study. It can be assumed the mortality risk is influenced by tumours with a high degree of malignancy whose share in the number of melanomas remains roughly constant. CONCLUSION: The early diagnosis of cancer, the inclusion of increasingly larger groups of the populations in the regions described, and constant mortality rates for men and women during the period of observation all relate the use of early diagnosis. If the efficiency of population screening is measured against the outcome reduction of the mortality rate, it appears to be sufficient to continue cancer early detection according to SGB V § 25. A preventive check-up is indicated for risk groups, e. g., those with a positive familiar history or if potentially malignant skin alterations have been diagnosed.

[Enhanced recovery after surgery (ERAS®) in cardiac anesthesia]. / Enhanced Recovery After Surgery (ERAS®) in der Kardioanästhesie.

Enhanced Recovery After Cardiac Surgery (ERACS) is a multidisciplinary and multiprofessional treatment approach in cardiac surgery. Recently, a transfer and adaptation of enhanced recovery after surgery (ERAS) protocols from other disciplines, such as colorectal surgery, to cardiac surgery has been performed in different settings. First, prehabilitation programs have been established and investigated to improve patients' physical, psychological and nutritional status including treatment of preoperative anemia. Second, intraoperative therapeutic steps are described, such as infection reduction bundles, rigid sternal closure and guidance of perioperative anesthesia. For this, the use of short-acting agents, goal-directed fluid management and multimodal anesthesia are among the important measures. Third, early recovery and restoration of patient autonomy are achieved with early extubation and mobilization, efficient postoperative analgesia and diagnosis and treatment of delirium.The introduction of an ERACS protocol is a team effort requiring a protocol adapted to the institutional conditions and a willingness to perform a shift of culture in perioperative care. So far, the successful establishment of ERACS protocols in minimally invasive cardiac surgery has been reported and encourages the development of protocols of specific patient groups, such as pediatric cardiac surgery or left ventricular assist device implantation.

Usage of C-Reactive Protein Testing in the Diagnosis and Monitoring of Psoriatic Arthritis (PsA): Results from a Real-World Survey in the USA and Europe.

INTRODUCTION: C-reactive protein (CRP) is an important non-specific marker of both acute and chronic inflammation and can be elevated in patients with psoriatic arthritis (PsA). However, the use of CRP testing in the management of PsA can vary. This study investigated how CRP testing is implemented in real-world clinical practice for disease management of PsA. METHODS: A point-in-time survey of rheumatologists and dermatologists and their next six consulting patients with PsA was conducted in France, Germany, Italy, Spain, UK (EU5), and the USA between June and August 2018. Use of CRP testing was obtained by asking the physician to state (yes/no) whether CRP was used to aid PsA diagnosis and/or to monitor the patient's disease activity. The number of CRP tests conducted in the last 12 months for each patient enrolled was provided. RESULTS: Data were collected for 2270 patients (USA, n = 595; EU5, n = 1675). In the EU5, CRP testing was conducted to aid diagnosis in 78.7% of patients (vs. 43.4% in USA) and CRP was used to monitor disease activity in 72.0% (vs. 34.6% in USA). The majority (80.9%) of patients in the EU5 had at least one CRP test in the last 12 months compared to 42.9% in the USA. Patients treated by rheumatologists (vs. dermatologists) were at least 50% more likely to have CRP tested for monitoring purposes, this difference being most pronounced in the USA. In the EU5, CRP testing was conducted a mean ± standard deviation of 2.7 ± 1.7 times during the last 12 months, versus 2.0 ± 1.4 in the USA. CONCLUSIONS: CRP was more commonly used for the diagnosis and monitoring of PsA in Europe compared to the USA and was more commonly ordered by rheumatologists than dermatologists. In the absence of a better serum biomarker of inflammation, more data are needed to understand how CRP testing should be used in the diagnosis and management PsA.

Tularaemia in Berlin - two independent cases in travellers returning from central Anatolia, Turkey, February 2011.

Tularaemia, though rare, has recently been increasingly reported in Germany. Most cases are indigenous infections. This report describes two epidemiologically independent infections with Francisella tularensis subspecies holarctica detected in Berlin in February 2011 that were acquired in central Anatolia, Turkey. In Turkey, there have been repeated tularaemia outbreaks since 2000 and the disease should therefore be considered as a differential diagnosis in travellers returning from that country.

Two-color Kerr microscopy of two-dimensional materials with sub-picosecond time resolution.

We present a two-color Kerr microscopy system based on two electronically synchronized erbium-fiber laser oscillators with independently tunable emission energies spanning most of the visible spectrum. Combining a spatial resolution below 2 µm and sub-ps time resolution with high sensitivity and cryogenic sample temperatures, it is ideally suited for studying spin and valley dynamics in a wide range of two-dimensional materials. We illustrate its capabilities by studying a monolayer of the common semiconducting transition metal disulfide MoS2.

A Review of the Toxicity and Phytochemistry of Medicinal Plant Species Used by Herbalists in Treating People Living With HIV/AIDS in Uganda.

Introduction: Despite concerns about toxicity, potentially harmful effects and herb-drug interactions, the use of herbal medicines remains widely practiced by people living with HIV/AIDS (PLHIV) in Uganda. Objective: The objective of the paper was to comprehensively review the literature on the toxicity and chemical composition of commonly used medicinal plant species in treating PLHIV in Uganda. Methods: We reviewed relevant articles and books published over the last sixty years on ethnobotany, antiviral/anti-HIV activity, toxicity, phytochemistry of Vachellia hockii, Albizia coriaria, Bridelia micrantha, Cryptolepis sanguinolenta, Erythrina abyssinica, Gardenia ternifolia, Gymnosporia senegalensis, Psorospermum febrifugium, Securidaca longipendunculata, Warburgia ugandensis and Zanthoxylum chalybeum and their synonyms. We searched PubMed, Web of Science, Scopus, Science Direct and Google Scholar. Discussion: Most of the plant species reviewed apart from P. febrifugium, S. longipedunculata and C. sanguinolenta lacked detailed phytochemical analyses as well as the quantification and characterization of their constituents. Crude plant extracts were the most commonly used. However, purified/single component extracts from different plant parts were also used in some studies. The U87 human glioblastoma was the most commonly used cell line. Water, ethanol, methanol and DMSO were the commonest solvents used. In some instances, isolated purified compounds/extracts such as Cryptolepine and Psorospermin were used. Conclusion: Cytotoxicity varied with cell type, solvent and extract type used making it difficult for direct comparison of the plant species. Five of the eleven plant species namely, A. coriaria, C. sanguinolenta, G. ternifolia, P. febrifugium and Z. chalybeum had no cytotoxicity studies in animal models. For the remaining six plant species, the crude aqueous and ethanol extracts were mainly used in acute oral toxicity studies in mice. Herbalists reported only A. coriaria and W. ugandensis to cause toxic side effects in humans. However, selective cytotoxic plant extracts can potentially be beneficial as anticancer or anti-tumour drugs.

Repeated exposure of the oral mucosa over 12 months with cold plasma is not carcinogenic in mice.

Peri-implantitis may result in the loss of dental implants. Cold atmospheric pressure plasma (CAP) was suggested to promote re-osseointegration, decrease antimicrobial burden, and support wound healing. However, the long-term risk assessment of CAP treatment in the oral cavity has not been addressed. Treatment with two different CAP devices was compared against UV radiation, carcinogen administration, and untreated conditions over 12 months. Histological analysis of 406 animals revealed that repeated CAP exposure did not foster non-invasive lesions or squamous cell carcinoma (SCCs). Carcinogen administration promoted non-invasive lesions and SCCs. Molecular analysis by a qPCR screening of 144 transcripts revealed distinct inflammatory profiles associated with each treatment regimen. Interestingly, CAP treatment of carcinogen-challenged mucosa did not promote but instead left unchanged or reduced the proportion of non-invasive lesions and SCC formation. In conclusion, repeated CAP exposure of murine oral mucosa was well tolerated, and carcinogenic effects did not occur, motivating CAP applications in patients for dental and implant treatments in the future.

Dissipative wave packet dynamics of hydrophobic → hydrophilic site switching in phenol-Ar clusters.

We analyze the results of recent pump-probe experiments on the site-switching dynamics of Ar within cationic phenol-Ar(2) clusters. A reaction-path model is employed for the wave packet dynamics. It is shown that the mechanism of energy dissipation is to be included to understand the features of the transient signals. Therefore, a simple recipe to include energy relaxation to the quantum dynamics is introduced. It is then possible to reproduce the measured pump-probe signals by adjustment of only two parameters.

Spotlight on measles 2010: preliminary report of an ongoing measles outbreak in a subpopulation with low vaccination coverage in Berlin, Germany, January-March 2010.

Since early January 2010, Berlin has been experiencing a measles outbreak with 62 cases as of 31 March. The index case acquired the infection in India. In recent years, measles incidence in Berlin has been lower than the German average and vaccination coverage in school children has increased since 2001. However, this outbreak involves schools and kindergartens with low vaccination coverage and parents with critical attitudes towards vaccination, which makes the implementation of public health interventions challenging.

Indigenous traditional knowledge of medicinal plants used by herbalists in treating opportunistic infections among people living with HIV/AIDS in Uganda.

ETHNOPHARMACOLOGICAL RELEVANCE: Currently, more than two thirds of the world's 36.9 million people living with HIV/AIDS reside in Sub-Saharan Africa. Opportunistic infections (OI) associated with HIV are the single most important cause of mortality and morbidity among HIV/AIDS patients in poor countries. There is widespread use of medicinal plant species to manage the HIV infection and it's associated OI in Uganda, even by patients already on antiretroviral drugs (ARV). However, much of this information remains undocumented and unverified. AIM OF STUDY: The aim of this study was to systematically and comprehensively document the traditional indigenous knowledge and practices associated with the management of HIV/AIDS infections by herbalists in Uganda. METHODS: Ethnobotanical data were collected using semi-structured interviews and questionnaires. Ninety traditional medicine practitioners (TMP) or herbalists were interviewed in Arua, Dokolo, Mbale, Bushenyi, Iganga, Rakai, Luwero and Kaabong districts to gather information on the plant species used. Data were analysed and presented using descriptive statistics and the Informant Consensus Factor. RESULTS: We documented 236 medicinal plant species from 70 families and 201 genera. Acacia was the most widely represented genus with five species. The most frequently used medicinal plant species for treating various OI were Erythrina abyssinica (45), Warburgia ugandensis (43), Zanthoxylum chalybeum (38), Acacia hockii (37), Mangifera indica (36), Aloe vera (35), Albizia coriaria (34), Azadirachta indica (32), Psorospermum febrifugum (27) Vernonia amygdalina (22) and Gymnosporia senegalensis (21). Some of the plant species were used for treating all the OI mentioned. There is a high degree of consensus among the TMP on which plant species they use for the different OI, even though they are geographically separated. Herbalists contribute to the widespread practice of simultaneously using herbal medicines and ARV. Some TMP are also engaged in dangerous practices like injecting patients with herbs and encouraging simultaneous use of herbs and ARV. Although the TMP relied on biomedical laboratory diagnoses for confirming the patients' HIV sero status, they were familiar with the signs and symptoms of HIV/AIDS. CONCLUSION: There is wide spread use of a rich diversity of medicinal plants species and practices by TMP to manage OI in HIV/AIDS patients in Uganda.

Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis.

Here, we describe the isolation of adenine nucleotide translocase-1 (ANT-1) in a screen for dominant, apoptosis-inducing genes. ANT-1 is a component of the mitochondrial permeability transition complex, a protein aggregate connecting the inner with the outer mitochondrial membrane that has recently been implicated in apoptosis. ANT-1 expression led to all features of apoptosis, such as phenotypic alterations, collapse of the mitochondrial membrane potential, cytochrome c release, caspase activation, and DNA degradation. Both point mutations that impair ANT-1 in its known activity to transport ADP and ATP as well as the NH(2)-terminal half of the protein could still induce apoptosis. Interestingly, ANT-2, a highly homologous protein could not lead to cell death, demonstrating the specificity of the signal for apoptosis induction. In contrast to Bax, a proapoptotic Bcl-2 gene, ANT-1 was unable to elicit a form of cell death in yeast. This and the observed repression of apoptosis by the ANT-1-interacting protein cyclophilin D suggest that the suicidal effect of ANT-1 is mediated by specific protein-protein interactions within the permeability transition pore.