Reversibility of Red blood Cell deformation

The ability of cells to undergo reversible shape changes is often crucial to their survival. For Red Blood Cells (RBCs), irreversible alteration of the cell shape and flexibility often causes anemia. Here we show theoretically that RBCs may react irreversibly to mechanical perturbations because of tensile stress in their cytoskeleton. The transient polymerization of protein fibers inside the cell seen in sickle cell anemia or a transient external force can trigger the formation of a cytoskeleton-free membrane protrusion of micrometer dimensions. The complex relaxation kinetics of the cell shape is shown to be responsible for selecting the final state once the perturbation is removed, thereby controlling the reversibility of the deformation. In some case, tubular protrusion are expected to relax via a peculiar "pearling instability".Comment: 4 pages, 3 figure

Torfmineralisierung und Corg-Verluste in bewaldeten Niedermoorböden

Vor dem Hintergrund der Anpassung der Landnutzung an den Klimawandel stehen sowohl Moore als auch Wälder im Fokus der wissenschaftlichen und politischen Wahrnehmung, da sie bedeutende und gefährdete terrestrische C-Speicher darstellen. Bewaldung fördert über das Baumwurzelwerk die Belüftung des Bodens und demzufolge sind die Bedingungen für die Torfmineralisierung in bewaldeten Moorböden günstiger als bei vergleichbaren Standortbedingungen unter Grünland. Um das Ausmaß der Torfmineralisierung und damit potenzieller Corg‑Verluste von bewaldeten Niedermoorböden aufzuklären, wurde im Eldequellgebiet/Mecklenburg-Vorpommern ein Landnutzungs- und Zeitvergleich von bewaldeten und als Grünland genutzten Moorböden mit jahrzehntelang persistenter Nutzung durchgeführt. Dazu wurden Niedermoorböden in unterschiedlich stark entwässerten Teilgebieten bezüglich der Zersetzungsgrade nach von Post, der Corg/Nt‑Verhältnisse, der Corg-Gehalte und der Corg-Speicher im Tiefenprofil verglichen, zudem wurden die Permeabilität der Oberböden und die Horizontierung untersucht. Die Entwässerungstiefe wurde als wesentlicher Einflussfaktor auf die Torfmineralisierung und Corg‑Verluste bestätigt, zudem konnte das Ausmaß der erhöhten Torfmineralisierung und Corg‑Verluste unter Wald im Untersuchungsgebiet mit mäßiger Entwässerung quantifiziert und im Tiefenprofil differenziert werden

A common NYX mutation in Flemish patients with X linked CSNB

Aims: The Schubert-Bornschein type of complete congenital stationary night blindness (CSNB) is a genetically heterogeneous retinal disorder. It is characterised by a non-progressive disease course, often associated with high myopia and nystagmus. So far, mutations in two genes, NYX (nyctalopin) and GRM6 (metabotropic glutamate receptor 6) have been associated with this form of CSNB. The purpose of this study was to identify the genetic defect in affected male patients from Flemish families with complete CSNB. Methods: Probands with CSNB from three large Flemish families underwent ophthalmological examination. DNA was extracted from peripheral blood, and the coding region of NYX along with parts of the 5'UTR and 3'UTR and intronic regions covering the splice sites were PCR amplified and sequenced. Results: In the affected individuals of three Flemish families with the complete form of CSNB a novel NYX mutation, c.855delG was identified. This deletion is predicted to lead to a frameshift mutation, p. Asp286ThrfsX62 causing a premature stop codon. Conclusion: Previously, both single families with different mutations in NYX as well as different families with an identical mutation, suggestive of a founder mutation, have been described. The c.855delG deletion in NYX seems to be a common mutation associated with CSNB in the Flemish population from Belgium. Thus, we suggest performing diagnostic testing for CSNB in the Flemish population initially directed towards the identification of this mutation. Subsequent screening for other mutations in NYX or GRM6 could be performed as a second step

Peripapillary Sparing With Near Infrared Autofluorescence Correlates With Electroretinographic Findings in Patients With Stargardt Disease

PURPOSE: To evaluate the correlation between the quantification of peripapillary sparing and electroretinogram (ERG) outcomes in autosomal recessive Stargardt disease (STGD1). METHODS: Near infrared fundus autofluorescence (NIR-FAF) images of 101 eyes of 101 patients were retrospectively reviewed. Peripapillary sparing was assessed both qualitatively and quantitatively. The area of spared tissue (AST) was calculated in a 1-mm-wide ring around the optic disc after binarization of the 55\ub0 NIR-FAF. These measurements were correlated with the presence of normal ERG (group I), abnormal photopic responses (group II), or abnormal photopic and scotopic responses (group III). RESULTS: AST showed significant correlations with ERG groups (R = -0.802, P < 0.001). While qualitative assessment of peripapillary sparing (i.e., present or not) also showed a significant correlation with ERG groups (R = -0.435, P < 0.001), it was weaker than by AST quantification. The ordinal regression analysis showed that the increase in AST was associated with a decrease in the odds of belonging to ERG groups II and III, with an odds ratio of 0.82 (95% confidence interval [CI] 0.78-0.87), P < 0.001. CONCLUSIONS: The AST around the optic disc in eyes with STGD1 correlates with the impairment of photoreceptors as shown in the ERG. If replicated in future longitudinal studies, the quantification of peripapillary sparing may prove to be a useful parameter for evaluating the visual prognosis of these eyes

Konzept zur Ermittlung und Beurteilung der Kohlenstoffspeicher urbaner Böden am Beispiel Berlins

Städte sind Hotspots anthropogener CO2-Emissionen. Sie besitzen daher eine besondere Verantwortung für die Umsetzung von Maßnahmen und Strategien zur Vermeidung von Treibhausgasemissionen. Ein systematisches Management der C-Speicher der Berliner Stadtnatur (Boden und Vegetation) fehlt bisher – trotz großen Potenzials. Übergeordnetes Ziel des Projektes ist es, den städtischen Klimaschutz über den Schutz und die Entwicklung der C-Speicher von Böden und grüner Infrastruktur (Vegetation) und damit die Aufnahme und Fixierung von atmosphärischem CO2 zu stärken. Das Forschungsprojekt NatKoS („natürliche Kohlenstoffspeicher“) erarbeitet von 2016–2019 eine belastbare Daten- und Bewertungsgrundlage für die Corg-Speicher der Böden und der Vegetation in Berlin. Die Heterogenität und Eigenheiten der urbanen Böden und die damit verbundenen Schwierigkeiten sind eine besondere Herausforderung bei der Konzipierung der Datenerhebung und Bodenbewertung. Das Konzept soll eine Differenzierung nach städtischen Nutzungsformen, ausgewählten Bodeneigenschaften sowie der Schutzwürdigkeit der Böden ermöglichen. Historische Analysen der Flächennutzung unterstützen zudem die Entwicklungsprognosen für die Corg-Speicher bei städtebaulichen Projekten oder sonstigen Flächennutzungsplanungen. Die Forschungsergebnisse besitzen daher eine große Planungsrelevanz für die Stadtentwicklung mit dem Ziel „klimaneutrales Berlin 2050“

Aetiology of resuscitated out-of-hospital cardiac arrest treated at hospital

Introduction: Precipitating aetiology of out-of-hospital cardiac arrest (OHCA), as confirmed by diagnostic testing or autopsy, provides important insights into burden of OHCA and has potential implications for improving OHCA survivorship. This study aimed to describe the aetiology of nontraumatic resuscitated OHCAs treated at hospital within a local health network according to available documentation, and to investigate dierences in outcome between aetiologies. Methods: Observational retrospective cohort study of consecutive OHCA treated at hospital within a local health network between 2011–2016. Cases without sustained ROSC ( 20 minutes), unverified cardiac arrest, and retrievals to external acute care facilities were excluded. A single aetiology was determined from the hospital medical record and available autopsy results. Survival to hospital discharge was compared between adjudicated aetiologies. Results: In the 314 included cases, distribution of precipitating aetiology was 53% cardiac, 18% respiratory, 3% neurological, 6% toxicological, 9% other, and 11% unknown. A presumed cardiac pre-hospital diagnosis was assigned in 235 (84%) cases, 20% of which were incorrect after exclusion of unknown cases. Rates of survival to hospital discharge varied significantly across aetiologies: cardiac 64%, respiratory 21%, neurological 0%, toxicological 58%, other 32% (p < 0.001). A two-fold dierence in survival was observed between cardiac and non-cardiac aetiologies (64% versus 29%, excluding unknown, p < 0.001). Conclusions: Non-cardiac aetiologies represented a substantial burden of resuscitated OHCA treated at hospital within a local health network and were associated with poor outcome. The results confirmed that true aetiology was not evident on initial examination in 1 in 5 cases with a pre-hospital cardiac diagnosis.M.R. Wittwer, C. Zeitz, J.F. Beltrame, M.A. Arstal

Prevalence of ABCA4 Deep-Intronic Variants and Related Phenotype in An Unsolved "One-Hit" Cohort with Stargardt Disease

We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlation with the genotype was performed in case a known intronic pathogenic variant was identified. All other variants found on the analyzed sequences were queried for minor allele frequency and possible pathogenicity by in silico predictions. The second mutated allele was found in 14 (20%) subjects. The three known deep-intronic variants found were c.5196+1137G>A in intron 36 (6 subjects), c.4539+2064C>T in intron 30 (4 subjects) and c.4253+43G>A in intron 28 (4 subjects). Even though the phenotype depends on the compound effect of the biallelic variants, a genotype-phenotype correlation suggests that the c.5196+1137G>A was mostly associated with a mild phenotype and the c.4539+2064C>T with a more severe one. A variable effect was instead associated with the variant c.4253+43G>A. In addition, two novel variants, c.768+508A>G and c.859-245_859-243delinsTGA never associated with Stargardt disease before, were identified and a possible splice defect was predicted in silico. Our study calls for a larger cohort analysis including targeted locus sequencing and 3D protein modeling to better understand phenotype-genotype correlations associated with deep-intronic changes and patients' selection for clinical trials

Cytomegalovirus disease in inflammatory bowel disease: epidemiology and disease characteristics in a large single-centre experience

BACKGROUND Patients with inflammatory bowel disease (IBD) show an increased risk of developing cytomegalovirus (CMV) disease because of immunosuppressive medication and malnutrition. Here, we aimed to investigate the prevalence and clinical characteristics of CMV disease in our cohort of IBD patients. PATIENTS AND METHODS We carried out a retrospective analysis of 1023 IBD patients treated at our IBD clinic at the University Hospital Zurich between 2007 and 2014. CMV disease was defined as a positive immunohistochemistry for CMV and 14 patients were identified. RESULTS The prevalence of CMV disease in our IBD cohort was 1.37%. Twelve patients had ulcerative colitis and two had Crohn's disease with colonic involvement. All patients who developed CMV disease received immunosuppressive medication or, as in one case, had HIV infection. The most used immunosuppressive medications were steroids and azathioprine. The most common therapeutic strategy was the consecutive use of ganciclovir and valganciclovir. Ten patients recovered and two were treatment refractory; among these, one required colectomy and two had a relapse. CONCLUSION CMV disease may influence the clinical course of IBD. There is probably an association between CMV disease and IBD-specific medication. Risk factors, epidemiology and therapeutic strategy need to be further investigated

BMJ Open Ophthalmol

Objective: Explore relationships between systemic exposure to intravitreal aflibercept injection (IAI) and systemic pharmacodynamic effects via post hoc analyses of clinical trials of IAI for neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DME). Methods and analysis: Adults from VGFT-OD-0702.PK (n=6), VGFT-OD-0512 (n= 5), VIEW 2 (n=1204) and VIVID-DME (n=404) studies were included. Validated ELISAs were used to measure concentrations of free and bound aflibercept (reported as adjusted bound) in plasma at predefined time points in each study. Non-compartmental analysis of concentration-time data was obtained with dense sampling in VGFT-OD-0702.PK and VGFT-OD-0512. Sparse sampling was used in VIEW 2 and VIVID-DME. Blood pressure or intrarenal function changes were also investigated. Results: Following intravitreal administration, free aflibercept plasma concentrations quickly decreased once maximum concentrations were achieved at 1-3 days postdose; pharmacologically inactive adjusted bound aflibercept concentrations increased over a longer period and reached plateau 7 days postdose. Ratios of free and adjusted bound aflibercept decreased over time. There were no meaningful changes in systolic/diastolic blood pressure over the duration of each study at all systemic aflibercept exposure levels. For all treatment arms in VIEW 2, there was no clinically relevant change in mean intrarenal function from baseline at week 52. Overall, incidence of systemic adverse events in VIEW 2 and VIVID-DME was low and consistent with the known safety profile of IAI. Conclusion: IAI administration was not associated with systemic effects in patients with nAMD or DME as measured by blood pressure or intrarenal function, two known pharmacologically relevant effects of anti-vascular endothelial growth factor

Physical and hydrological properties of peat as proxies for degradation of South African peatlands: Implications for conservation and restoration

The physical and hydrological properties of peat from seven peatlands in northern Maputaland (South Africa) were investigated and related to the degradation processes of peatlands in different hydrogeomorphic settings. The selected peatlands are representative of typical hydrogeomorphic settings and different stages of human modification from natural to severely degraded. Nineteen transects (141 soil corings in total) were examined in order to describe peat properties typical of the distinct hydrogeomorphic settings. We studied degree of decomposition, organic matter content, bulk density, water retention, saturated hydraulic conductivity and hydrophobicity of the peats. From these properties we derived pore size distribution, unsaturated hydraulic conductivity and maximum capillary rise. We found that, after drainage, degradation advances faster in peatlands containing wood peat than in peatlands containing radicell peat. Eucalyptus plantations in catchment areas are especially threatening to peatlands in seeps, interdune depressions and unchannelled valley bottoms. All peatlands and their recharge areas require wise management, especially valley-bottom peatlands with swamp forest vegetation. Blocking drainage ditches is indispensable as a first step towards achieving the restoration of drained peatland areas, and further measures may be necessary to enhance the distribution of water. The sensitive swamp forest ecosystems should be given conservation priority