Efficient electron-induced removal of oxalate ions and formation of copper nanoparticles from copper(II) oxalate precursor layers

Rueckriem K, Grotheer S, Vieker H, et al. Efficient electron-induced removal of oxalate ions and formation of copper nanoparticles from copper(II) oxalate precursor layers. BEILSTEIN JOURNAL OF NANOTECHNOLOGY. 2016;7:852-861.Copper(II) oxalate grown on carboxy-terminated self-assembled monolayers (SAM) using a step-by-step approach was used as precursor for the electron-induced synthesis of surface-supported copper nanoparticles. The precursor material was deposited by dipping the surfaces alternately in ethanolic solutions of copper(II) acetate and oxalic acid with intermediate thorough rinsing steps. The deposition of copper(II) oxalate and the efficient electron-induced removal of the oxalate ions was monitored by reflection absorption infrared spectroscopy (RAIRS). Helium ion microscopy (HIM) reveals the formation of spherical nanoparticles with well-defined size and X-ray photoelectron spectroscopy (XPS) confirms their metallic nature. Continued irradiation after depletion of oxalate does not lead to further particle growth giving evidence that nanoparticle formation is primarily controlled by the available amount of precursor

Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor

Although their contribution remains unclear, lipids may facilitate noncanonical routes of protein internalization into cells such as those used by cell-penetrating proteins. We show that protein C inhibitor (PCI), a serine protease inhibitor (serpin), rapidly transverses the plasma membrane, which persists at low temperatures and enables its nuclear targeting in vitro and in vivo. Cell membrane translocation of PCI necessarily requires phosphatidylethanolamine (PE). In parallel, PCI acts as a lipid transferase for PE. The internalized serpin promotes phagocytosis of bacteria, thus suggesting a function in host defense. Membrane insertion of PCI depends on the conical shape of PE and is associated with the formation of restricted aqueous compartments within the membrane. Gain- and loss-of-function mutations indicate that the transmembrane passage of PCI requires a branched cavity between its helices H and D, which, according to docking studies, precisely accommodates PE. Our findings show that its specific shape enables cell surface PE to drive plasma membrane translocation of cell-penetrating PCI

Disulfide bridge-dependent dimerization triggers FGF2 membrane translocation into the extracellular space

Fibroblast growth factor 2 (FGF2) exits cells by direct translocation across the plasma membrane, a type I pathway of unconventional protein secretion. This process is initiated by phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent formation of highly dynamic FGF2 oligomers at the inner plasma membrane leaflet, inducing the formation of lipidic membrane pores. Cell surface heparan sulfate chains linked to glypican-1 (GPC1) capture FGF2 at the outer plasma membrane leaflet, completing FGF2 membrane translocation into the extracellular space. While the basic steps of this pathway are well understood, the molecular mechanism by which FGF2 oligomerizes on membrane surfaces remains unclear. In the current study, we demonstrate the initial step of this process to depend on C95-C95 disulfide-bridge-mediated FGF2 dimerization on membrane surfaces, producing the building blocks for higher FGF2 oligomers that drive the formation of membrane pores. We find FGF2 with a C95A substitution to be defective in oligomerization, pore formation, and membrane translocation. Consistently, we demonstrate a C95A variant of FGF2 to be characterized by a severe secretion phenotype. By contrast, while also important for efficient FGF2 secretion from cells, a second cysteine residue on the molecular surface of FGF2 (C77) is not involved in FGF2 oligomerization. Rather, we find C77 to be part of the interaction interface through which FGF2 binds to the α1 subunit of the Na,K-ATPase, the landing platform for FGF2 at the inner plasma membrane leaflet. Using cross-linking mass spectrometry, atomistic molecular dynamics simulations combined with a machine learning analysis and cryo-electron tomography, we propose a mechanism by which disulfide-bridged FGF2 dimers bind with high avidity to PI(4,5)P2 on membrane surfaces. We further propose a tight coupling between FGF2 secretion and the formation of ternary signaling complexes on cell surfaces, hypothesizing that C95-C95-bridged FGF2 dimers are functioning as the molecular units triggering autocrine and paracrine FGF2 signaling

Women with HIV transitioning through menopause: Insights from the Swiss HIV Cohort Study (SHCS)

OBJECTIVES We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland. METHODS This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause. RESULTS Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation. CONCLUSIONS The median age of women living with HIV at menopause is around 2 years lower than that reported for HIV-negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause-associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy

Care for the chronically ill in Germany – The challenges during the COVID-19 pandemic

The COVID-19 pandemic is posing major challenges to the health care sector. This scoping review compiles evidence concerning changes to health care service availability and utilisation as well as possible impacts on health for selected groups of chronically ill people in Germany. The focus is on cancer, cardiovascular diseases, diabetes mellitus and mental disorders. Most empirical data available concerned inpatient care and showed a clear decline in the utilisation of inpatient treatments in March and April 2020 in the areas of oncology and cardiology as well as in mental health. For cardiovascular emergencies such as heart attack and stroke, a decline was observed especially regarding less serious cases. Although there were indications of treatment delays, there was no evidence thus far that emergency care had been generally compromised due to adjustments to inpatient care capacities. In the outpatient setting, extensive adjustments to health care services availability were observed for all disease groups considered. Overall, very limited empirical data were available. In particular, hardly any data were available on how changes in care impacted population health. There is an urgent need for continuous surveillance and evaluation based on health care and epidemiological data.Peer Reviewe

Care for the chronically ill in Germany – The challenges during the COVID-19 pandemic

The COVID-19 pandemic is posing major challenges to the health care sector. This scoping review compiles evidence concerning changes to health care service availability and utilisation as well as possible impacts on health for selected groups of chronically ill people in Germany. The focus is on cancer, cardiovascular diseases, diabetes mellitus and mental disorders. Most empirical data available concerned inpatient care and showed a clear decline in the utilisation of inpatient treatments in March and April 2020 in the areas of oncology and cardiology as well as in mental health. For cardiovascular emergencies such as heart attack and stroke, a decline was observed especially regarding less serious cases. Although there were indications of treatment delays, there was no evidence thus far that emergency care had been generally compromised due to adjustments to inpatient care capacities. In the outpatient setting, extensive adjustments to health care services availability were observed for all disease groups considered. Overall, very limited empirical data were available. In particular, hardly any data were available on how changes in care impacted population health. There is an urgent need for continuous surveillance and evaluation based on health care and epidemiological data.Peer Reviewe

Preoperative Imaging with [F-18]-Fluorocholine PET/CT in Primary Hyperparathyroidism

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. F-18-Fluorocholine positron emission tomography/computed tomography (F-18-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received F-18-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes F-18-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of F-18-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of F-18-FCH PET/CT for successful surgical guidance

Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery

Motivation: Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult. Results: We present SignaLink, a database containing 8 major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster, and humans. Based on 170 review and approx. 800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the 8 pathways can cross-talk. We quantified the possible tissue- and cancer-specific activity of cross-talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery. Conclusions: We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease and underscore its importance in network-based drug target selection. Availability: http://SignaLink.orgComment: 9 pages, 4 figures, 2 tables and a supplementary info with 5 Figures and 13 Table

Brief Report: Does Menopause Transition Influence Viral Suppression and Adherence in Women Living With HIV?

BACKGROUND: Increasing numbers of women living with HIV transition through menopause. It is unclear whether this transition has an impact on treatment adherence, viral suppression, psychiatric comorbidities, or drug use. We aimed at examining adherence and viral suppression during the perimenopausal period and explored the influence of psychiatric comorbidities and active injection drug use (IDU). SETTING: Retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. METHODS: We explored perimenopausal and postmenopausal trends of viral blips, low-level viremia, viral failure, adherence, psychiatric comorbidities, and IDU using interrupted time series models. RESULTS: Rates of depression and psychiatric care increased during perimenopause before decreasing afterward. Negative treatment outcomes such as viral blips, low-level viremia, viral failure, and low adherence steadily declined while transitioning through menopause-this was also true for subgroups of women with depression, psychiatric treatment, and active IDU. CONCLUSIONS: Increased rates of depression and psychiatric care while transitioning through menopause do not result in lower rates of adherence or viral suppression in women living with HIV in Switzerland

Versorgung von chronisch Kranken in Deutschland - Herausforderungen in Zeiten der COVID-19-Pandemie

Die medizinische Versorgung wird durch die COVID-19-Pandemie vor große Herausforderungen gestellt. Das vorliegende Scoping Review trägt Hinweise auf bisherige Veränderungen der Versorgungsangebote und der Inanspruchnahme sowie mögliche gesundheitliche Folgen für ausgewählte Gruppen chronisch kranker Menschen in Deutschland zusammen. Der Fokus liegt auf Krebserkrankungen, Herz-Kreislauf-Erkrankungen, Diabetes mellitus und psychischen Störungen. Empirische Daten liegen überwiegend für den stationären Bereich vor und zeigen einen deutlichen Rückgang stationärer Behandlungen im März/April 2020 im Bereich der Onkologie und der Kardiologie sowie bei psychischen Störungen. Für kardiovaskuläre Notfälle wie Herzinfarkt und Schlaganfall wurde ein Rückgang vor allem bei leichteren Fällen beobachtet. Bislang liegen einige Hinweise auf verzögerte Inanspruchnahme, jedoch keine Hinweise auf Beeinträchtigung der Notfallversorgung durch Anpassung stationärer Versorgungskapazitäten vor. Im ambulanten Bereich kam es für alle betrachteten Krankheitsgruppen zu umfassenden Anpassungen der Versorgungsangebote. Die empirische Datenlage ist insgesamt noch sehr begrenzt. Insbesondere liegen kaum Daten zu gesundheitlichen Auswirkungen durch Veränderungen in der Versorgung vor. Es besteht dringender Bedarf für kontinuierliche Begleit- und Evaluationsforschung auf der Basis von Versorgungsdaten und epidemiologischer Daten.Peer Reviewe