Humoral Immunity to Varicella Zoster Virus in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis Compared to Healthy Controls

Background: The prevalence of herpes zoster (HZ) is high in patients with rheumatic diseases. Systemic lupus erythematosus (SLE) doubles the risk for developing HZ. However, little is known about natural humoral immunity against varicella zoster virus (VZV) in patients with SLE. Hence, we compared VZV IgG antibody concentrations in a group of SLE patients with healthy controls and patients with rheumatoid arthritis (RA). Methods: n = 56 patients with SLE, n = 54 patients with RA, and n = 56 healthy controls were included in this study. The VZV IgG antibody concentration was measured using an enzyme-linked immunosorbent assay (ELISA). The antibody concentrations were compared between the groups. Results: Overall IgG antibody titers for VZV in SLE patients were comparable to healthy controls but higher when compared to patients with rheumatoid arthritis (p = 0.0012). In consequence, antibody levels in controls were higher than in RA patients (p = 0.0097). Stratification by age revealed highest titers among SLE patients in the fourth life decade (p = 0.03 for controls, p = 0.0008 for RA patients) whereas RA patients in their sixth decade had the lowest antibody concentration (p = 0.03 for controls, p = 0.04 for SLE patients). Regarding the individual HZ history, antibody levels of SLE patients with a positive history exceeded all other groups. Conclusions: Although humoral VZV immunity in SLE patients is comparable to healthy controls it seems to be pronounced in young SLE patients between 30 and 39. The lowest VZV IgG levels were found in RA patients. HZ seems to induce antibody production, particularly in patients with SLE. Immunological processes might contribute to VZV antibody levels in SLE patients, but further investigations are needed to substantiate this hypothesis. Even though the increased HZ prevalence seems to be independent of humoral immunity in SLE patients, reduced humoral immunity might contribute to HZ in RA patients. The available HZ subunit vaccination might be an appropriate way to reduce the HZ risk in patients with rheumatic diseases

Individual health services

Background: The German statutory health insurance (GKV) reimburses all health care services that are deemed sufficient, appropriate, and efficient. According to the German Medical Association (BÄK), individual health services (IGeL) are services that are not under liability of the GKV, medically necessary or recommendable or at least justifiable. They have to be explicitly requested by the patient and have to be paid out of pocket. Research questions: The following questions regarding IGeL in the outpatient health care of GKV insurants are addressed in the present report: What is the empirical evidence regarding offers, utilization, practice, acceptance, and the relation between physician and patient, as well as the economic relevance of IGeL? What ethical, social, and legal aspects are related to IGeL? For two of the most common IGeL, the screening for glaucoma and the screening for ovarian and endometrial cancer by vaginal ultrasound (VUS), the following questions are addressed: What is the evidence for the clinical effectiveness? Are there sub-populations for whom screening might be beneficial? Methods: The evaluation is divided into two parts. For the first part a systematic literature review of primary studies and publications concerning ethical, social and legal aspects is performed. In the second part, rapid assessments of the clinical effectiveness for the two examples, glaucoma and VUS screening, are prepared. Therefore, in a first step, HTA-reports and systematic reviews are searched, followed by a search for original studies published after the end of the research period of the most recent HTA-report included. Results: 29 studies were included for the first question. Between 19 and 53% of GKV members receive IGeL offers, of which three-quarters are realised. 16 to 19% of the insurants ask actively for IGeL. Intraocular tension measurement is the most common single IGeL service, accounting for up to 40% of the offers. It is followed by ultrasound assessments with up to 25% of the offers. Cancer screening and blood or laboratory services are also frequent and represent a major proportion of the demand. The ethical, social, and legal aspects discussed in the context of IGeL concern eight subject areas: 1. autonomous patient decisions versus obtrusion, 2. commercialization of medicine, 3. duty of patient information, 4. benefit, evidence, and (quality) control, 5. role and relation of physicians and patients, 6. relation to the GKV, 7. social inequality, 8. formally correct performance. For glaucoma screening, no randomized controlled trial (RCT) is identified that shows a patient relevant benefit. For VUS three RCT are included. However, they do not yet present mortality data concerning screened and non-screened persons. VUS screening shows a high degree of over-diagnosis in turn leading to invasive interventions. To diagnose one invasive carcinoma, 30 to 35 surgical procedures are necessary. Conclusion: IGeL are a relevant factor in the German statutory health care system. To provide more transparency, the requests for evidence-based and independent patient information should be considered. Whether official positive and negative-lists could be an appropriate instrument to give guidance to patients and physicians, should be examined. Generally, IGeL must be seen in the broader context of the discussions about the future design and development of the German health care system

Limited Value of Bladder Wash Cytology During Follow-Up of Patients With Non-muscle Invasive Bladder Cancer

Aims We aimed to assess the performance of bladder wash cytology (BWC) in daily clinical practice in a pure follow-up cohort of patients previously diagnosed with non-muscle invasive bladder cancer (NMIBC). Materials and methods We analyzed 2064 BWCs derived from 314 patients followed for NMIBC (2003-2016). Follow-up investigations were performed using cystoscopy (CS) in combination with BWC. Patients with suspicious CS and/or positive BWC underwent bladder biopsy or transurethral resection. BWC was considered positive if malignant or suspicious cells were reported. Sensitivity (Sn) and specificity (Sp) were calculated for the entire cohort and separately for low-grade (LG) and high-grade (HG) tumors, and carcinoma in situ (CIS) subgroups. Results A total of 95 recurrences were detected, of which only three were detected by BWC alone. Overall, Sn and Sp of BWC were 17.9% and 99.5%, respectively. For LG disease, these numbers were 14.0% and 100%, and for HG disease, these were 22.2% and 99.1%, respectively. For patients with CIS at initial diagnosis, Sn and Sp were 11.0% and 71.4%, respectively. For isolated primary CIS, Sn was 50.0%, and Sp was 98.2%. Conclusion Routine use of BWC in the follow-up for NMIBC is of limited value even in HG tumors. In the presence of isolated primary CIS, adjunct BWC might be justified

On the mechanisms of spontaneous growth of III-nitride nanocolumns by plasma-assisted molecular beam epitaxy

A study of the GaN nanocolumns nucleation and growth by molecular beam epitaxy on Si(1 1 1) is presented. Ga droplets with different diameters (340–90 nm) were deposited on the substrate, prior to growth, to determine any effect on the nanocolumns size and distribution. Results indicate that there is no difference in nanocolumnar size and density whether Ga droplets are used or not, meaning that Ga droplets do not act as catalysts for the nanocolumns nucleation. In addition, Ga droplets were never observed on the nanocolumn tips upon growth termination. These findings rule out the vapor–liquid–solid mechanism. Instead, driven by a strong lattice mismatch nanocolumnar nucleation occurs spontaneously by Volmer–Weber growth mechanism, whereas nitrogen excess prevents the nucleation sites coalescence. Further nanocolumnar growth proceeds by direct Ga incorporation on the nanocolumns top and by Ga diffusion along the nanocolumns sidewalls up to their apex. Related to this diffusion mechanism, we found that Ga droplets, when used, may act as reservoirs to feed Ga atoms to the neighboring nanocolumns. Nanocolumns preserve a constant diameter if growth conditions are not modified because of a strong metal ad-atom diffusion length along their sidewalls. The effect of using AlN buffer layers on the nanocolumnar growth and morphology is also addressed

Glacial meltwater effects on the carbon cycle of Scoresby Sund (Greenland), the world's largest fjord system

Climate change induced mass loss of the Greenland Ice Sheet increases the amount of meltwater, which is mainly released into the numerous fjords along the coast of Greenland. Due to its low salinity and high silt load, meltwater can profoundly affect the biogeochemical cycling of carbon. We visited the world’s largest fjord system, Scoresby Sund at the eastern coast of Greenland, and its northernmost branch, Nordvestfjord, in the summer of 2016 for investigating biogeochemical carbon cycling. The data reveal that meltwater limited the productivity by inhibiting the resupply of nutrients to the surface and by shadowing the upper part of the water column by the introduction of silts. These silts, though, increased the export of organic carbon to depth by ballasting the sinking organic particles. While the region close to the fjord entrance was influenced by shelf waters, the water column within Nordvestfjord was significantly modulated by meltwater input from a number of marine- and land-terminating glaciers. Our results show that there was a clear gradient from a productive system with efficient remineralization at the mouth of the fjord to a less productive system with a high carbon export towards the inner fjord parts. These results imply that Scoresby Sund can be seen as a hotspot of carbon burial

Influence of Glacial Meltwater on Summer Biogeochemical Cycles in Scoresby Sund, East Greenland

Greenland fjords receive considerable amounts of glacial meltwater discharge from the Greenland Ice Sheet due to present climate warming. This impacts the hydrography, via freshening of the fjord waters, and biological processes due to altered nutrient input and the addition of silts. We present the first comprehensive analysis of the summer carbon cycle in the world's largest fjord system situated in southeastern Greenland. During a cruise onboard RV Maria S. Merian in summer 2016, we visited Scoresby Sund and its northernmost branch, Nordvestfjord. In addition to direct measurements of hydrography, biogeochemical parameters and sediment trap fluxes, we derived net community production (NCP) and full water column particulate organic carbon (POC) fluxes, and estimated carbon remineralization from vertical flux attenuation. While the narrow Nordvestfjord is influenced by subglacial and surface meltwater discharge, these meltwater effects on the outer fjord part of Scoresby Sund are weakened due to its enormous width. We found that subglacial and surface meltwater discharge to Nordvestfjord significantly limited NCP to 32–36 mmol C m−2 d−1 compared to the outer fjord part of Scoresby Sund (58–82 mmol C m−2 d−1) by inhibiting the resupply of nutrients to the surface and by shadowing of silts contained in the meltwater. The POC flux close to the glacier fronts was elevated due to silt-ballasting of settling particles that increases the sinking velocity and thereby reduces the time for remineralization processes within the water column. By contrast, the outer fjord part of Scoresby Sund showed stronger attenuation of particles due to horizontal advection and, hence, more intense remineralization within the water column. Our results imply that glacially influenced parts of Greenland's fjords can be considered as hotspots of carbon export to depth. In a warming climate, this export is likely to be enhanced during glacial melting. Additionally, entrainment of increasingly warmer Atlantic Water might support a higher productivity in fjord systems. It therefore seems that future ice-free fjord systems with high input of glacial meltwater may become increasingly important for Arctic carbon sequestration

Impairment of Immunoproteasome Function by β5i/LMP7 Subunit Deficiency Results in Severe Enterovirus Myocarditis

Proteasomes recognize and degrade poly-ubiquitinylated proteins. In infectious disease, cells activated by interferons (IFNs) express three unique catalytic subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform, the immunoproteasome (IP). The in vivo function of IPs in pathogen-induced inflammation is still a matter of controversy. IPs were mainly associated with MHC class I antigen processing. However, recent findings pointed to a more general function of IPs in response to cytokine stress. Here, we report on the role of IPs in acute coxsackievirus B3 (CVB3) myocarditis reflecting one of the most common viral disease entities among young people. Despite identical viral load in both control and IP-deficient mice, IP-deficiency was associated with severe acute heart muscle injury reflected by large foci of inflammatory lesions and severe myocardial tissue damage. Exacerbation of acute heart muscle injury in this host was ascribed to disequilibrium in protein homeostasis in viral heart disease as indicated by the detection of increased proteotoxic stress in cytokine-challenged cardiomyocytes and inflammatory cells from IP-deficient mice. In fact, due to IP-dependent removal of poly-ubiquitinylated protein aggregates in the injured myocardium IPs protected CVB3-challenged mice from oxidant-protein damage. Impaired NFκB activation in IP-deficient cardiomyocytes and inflammatory cells and proteotoxic stress in combination with severe inflammation in CVB3-challenged hearts from IP-deficient mice potentiated apoptotic cell death in this host, thus exacerbating acute tissue damage. Adoptive T cell transfer studies in IP-deficient mice are in agreement with data pointing towards an effective CD8 T cell immune. This study therefore demonstrates that IP formation primarily protects the target organ of CVB3 infection from excessive inflammatory tissue damage in a virus-induced proinflammatory cytokine milieu

Ευρετικές προσεγγίσεις του μοναδιάστατου προβλήματος πακετοποίησης

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and non-pleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data