Stronger and More Vulnerable: A Balanced View of the Impacts of the NICU Experience on Parents

For parents, the experience of having an infant in the NICU is often psychologically traumatic. No parent can be fully prepared for the extreme stress and range of emotions of caring for a critically ill newborn. As health care providers familiar with the NICU, we thought that we understood the impact of the NICU on parents. But we were not prepared to see the children in our own families as NICU patients. Here are some of the lessons our NICU experience has taught us. We offer these lessons in the hope of helping health professionals consider a balanced view of the NICU's impact on families

Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology

INTRODUCTION Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected. DISCUSSION The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages. Highlights Using surface-based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE-Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort Aβ oligomers were significantly elevated in mild cognitive impairment (MCI) Amyloid-positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid-negative control group Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanism

Zirkulierende Wirbelschichtfeuerung Verbrennung von schwierigen ost- und westelbischen Rohbraunkohlen mit dem Ziel des prozessintegrierten Umweltschutzes Abschlussbericht

In this work, the use for energy purposes of difficult East German brown coals is to be examined in an experimental plant with circulation fluidized bed combustion. The inherent process mechanism for retaining harmful substances is to be shown, in order to make a contribution to environmentally careful combustion of these coals. The east and west Elbe coals used differ above all in ash, water and sulphur content, and in calorific value. The reproduceable experimental results obtained are the proof that the experimental plant correctly reproduces the processes typical of ZWSF in industrial plants. The primary side effect of the course of the temperature in the parts of the plant, the reactor, transverse draught, cyclone and siphon was determined, which is a basic precondition for the emission of harmful substances. Fuels with a water content of 20% (socalled briquetting coal) was burnt without problems. The carbon and CO values achieved for this size of plant are very good. The effect of the NO_x emission due to different amounts of excess air and the changed flows of solids could be found. Only the degree of binding achieved with the fuel ash was determined for SO_2 emission. Above all using east Elbe brown coal, good results were achieved, which are due to the low sulphur and high CaO content of the coals. When using west Elbe brown coal, because of the appreciably higher sulphur content, an additive is required. When burning west Elbe coal, the effect of different water contents on combustion and the emission of harmful substances was researched in more detail. (orig./HS)In dieser Arbeit sollte der energetische Einsatz schwieriger ostdeutscher Braunkohlen in einer Versuchsanlage mit zirkulierender Wirbelschichtfeuerung untersucht werden. Dabei sollten die prozesseigenen Mechanismen zur Schadstoffrueckhaltung aufgezeigt werden, um einen Beitrag zur umweltschonenden Verbrennung dieser Kohlen zu leisten. Die zum Einsatz gekommenen ost- und westelbischen Kohlen unterscheiden sich vor allem in Asche-, Wasser- und Schwefelgehalt sowie im Heizwert. Mit den gewonnenen reproduzierbaren Versuchsergebnissen ist der Nachweis erbracht worden, dass die Versuchsanlage die ZWSF typischen Vorgaenge von Industrieanlagen richtig wiedergibt. Es wurde die primaerseitige Beeinflussung der Temperaturverlaeufe in den Anlagenteilen, Reaktor, Querzug, Zyklon und Siphon ermittelt, die eine Grundvoraussetzung fuer die Schadstoffemission ist. Brennstoffe mit einem Wassergehalt von 20% (sogenannte Brikettierkohle) wurde problemlos verbrannt. Die dabei erreichten Kohlestoffumsaetze und CO-Werte sind fuer diese Anlagengroesse sehr gut. Die Beeinflussung der NO_x-Emission durch unterschiedliche Luftueberschuesse und geaenderte umlaufende Feststoffstroeme, konnte erbracht werden. Bei der SO_2-Emission wurde nur die mit der Brennstoffasche erzielten Einbindungsgrade ermittelt. Vor allem mit der ostelbischen Braunkohle wurden dabei gute Ergebnisse erzielt, die auf die niedrigen Schwefel- und hohen CaO-Gehalte der Kohlen zurueckzufuehren sind. Beim Einsatz von westelbischer Braunkohle ist wegen der deutlich hoeheren Schwefelgehalte die Zugabe eines Additives erforderlich. Bei der Verbrennung von westelbischer Kohle wurde der Einfluss verschiedener Wassergehalte auf die Verbrennung und die Schadstoffemissionen naeher erforscht. (orig./HS)SIGLEAvailable from TIB Hannover: F96B218+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Structure characterization of unexpected covalent O-sulfonation and ion-pairing on an extremely hydrophilic peptide with CE-MS and FT-ICR-MS

In this study, we characterized unexpected side-products in a commercially synthesized peptide with the sequence RPRTRLHTHRNR. This so-called peptide D3 was selected by mirror phage display against low molecular weight amyloid-β-peptide (Aβ) associated with Alzheimer’s disease. Capillary electrophoresis (CE) was the method of choice for structure analysis because the extreme hydrophilicity of the peptide did not allow reversed-phase liquid chromatography (RPLC) and hydrophilic interaction stationary phases (HILIC). CE-MS analysis, applying a strongly acidic background electrolyte and different statically adsorbed capillary coatings, provided fast and efficient analysis and revealed that D3 unexpectedly showed strong ion-pairing with sulfuric acid. Moreover, covalent O-sulfonation at one or two threonine residues was identified as a result of a side reaction during peptide synthesis, and deamidation was found at either the asparagine residue or at the C-terminus. In total, more than 10 different species with different m/z values were observed. Tandem-MS analysis with collision induced dissociation (CID) using a CE-quadrupole-time-of-flight (QTOF) setup predominantly resulted in sulfate losses and did not yield any further characteristic fragment ions at high collision energies. Therefore, direct infusion Fourier transform ion cyclotron resonance (FT-ICR) MS was employed to identify the covalent modification and discriminate O-sulfonation from possible O-phosphorylation by using an accurate mass analysis. Electron transfer dissociation (ETD) was used for the identification of the threonine O-sulfation sites. In this work, it is shown that the combination of CE-MS and FT-ICR-MS with ETD fragmentation was essential for the full characterization of this extremely basic peptide with labile modifications

All - d - Enantiomeric Peptide D3 Designed for Alzheimer’s Disease Treatment Dynamically Interacts with Membrane-Bound Amyloid-β Precursors

Alzheimer’s disease (AD) is a severe neurodegenerative pathology with no effective treatment known. Toxic amyloid-β peptide (Aβ) oligomers play a crucial role in AD pathogenesis. All-d-Enantiomeric peptide D3 and its derivatives were developed to disassemble and destroy cytotoxic Aβ aggregates. One of the D3-like compounds is approaching phase II clinical trials; however, high-resolution details of its disease-preventing or pharmacological actions are not completely clear. We demonstrate that peptide D3 stabilizing Aβ monomer dynamically interacts with the extracellular juxtamembrane region of a membrane-bound fragment of an amyloid precursor protein containing the Aβ sequence. MD simulations based on NMR measurement results suggest that D3 targets the amyloidogenic region, not compromising its α-helicity and preventing intermolecular hydrogen bonding, thus creating prerequisites for inhibition of early steps of Aβ conversion into β-conformation and its toxic oligomerization. An enhanced understanding of the D3 action molecular mechanism facilitates development of effective AD treatment and prevention strategies

Stronger and More Vulnerable: A Balanced View of the Impacts of the NICU Experience on Parents

For parents, the experience of having an infant in the NICU is often psychologically traumatic. No parent can be fully prepared for the extreme stress and range of emotions of caring for a critically ill newborn. As health care providers familiar with the NICU, we thought that we understood the impact of the NICU on parents. But we were not prepared to see the children in our own families as NICU patients. Here are some of the lessons our NICU experience has taught us. We offer these lessons in the hope of helping health professionals consider a balanced view of the NICU's impact on families

Adenosine regulation of alveolar fluid clearance

Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na(+) transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A(1)R), 2a (A(2a)R), 2b (A(2b)R), and 3 (A(3)R) adenosine receptors are present in rat and mouse lungs and alveolar type 1 and 2 epithelial cells (AT1 and AT2). Rat AT2 cells generated and produced cAMP in response to adenosine, and micromolar concentrations of adenosine were measured in bronchoalveolar lavage fluid from mice. Ussing chamber studies of rat AT2 cells indicated that adenosine affects ion transport through engagement of A(1)R, A(2a)R, and/or A(3)R through a mechanism that increases CFTR and amiloride-sensitive channel function. Intratracheal instillation of low concentrations of adenosine (≤10(−8)M) or either A(2a)R- or A(3)R-specific agonists increased alveolar fluid clearance (AFC), whereas physiologic concentrations of adenosine (≥10(−6)M) reduced AFC in mice and rats via an A(1)R-dependent pathway. Instillation of a CFTR inhibitor (CFTR(inh-172)) attenuated adenosine-mediated down-regulation of AFC, suggesting that adenosine causes Cl(−) efflux by means of CFTR. These studies report a role for adenosine in regulation of alveolar ion transport and fluid clearance. These findings suggest that physiologic concentrations of adenosine allow the alveolar epithelium to counterbalance active Na(+) absorption with Cl(−) efflux through engagement of the A(1)R and raise the possibility that adenosine receptor ligands can be used to treat pulmonary edema