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Ripples are a typical form of neural activity in hippocampal neural networks associated with the replay of episodic memories during sleep as well as sleep-related plasticity and memory consolidation. The emergence of ripples has been observed both dependent as well as independent of input from other brain areas and often coincides with dendritic spikes. Yet, it is unclear how input-evoked and spontaneous ripples as well as dendritic excitability affect plasticity and consolidation. Here, we use mathematical modeling to compare these cases. We find that consolidation as well as the emergence of spontaneous ripples depends on a reliable propagation of activity in feed-forward structures which constitute memory representations. This propagation is facilitated by excitable dendrites, which entail that a few strong synapses are sufficient to trigger neuronal firing. In this situation, stimulation-evoked ripples lead to the potentiation of weak synapses within the feed-forward structure and, thus, to a consolidation of a more general sequence memory. However, spontaneous ripples that occur without stimulation, only consolidate a sparse backbone of the existing strong feed-forward structure. Based on this, we test a recently hypothesized scenario in which the excitability of dendrites is transiently enhanced after learning, and show that such a transient increase can strengthen, restructure and consolidate even weak hippocampal memories, which would be forgotten otherwise. Hence, a transient increase in dendritic excitability would indeed provide a mechanism for stabilizing memories.

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PURPOSE: Orbital exenteration of periocular tumors complicated by orbital invasion is a heavy burden for patients and leads to disfiguring cosmesis and loss of vision. Here, we report our experience with globe-sparing surgery in a series of patients with periocular malignancies other than basal cell carcinoma (BCC), all exhibiting anterior orbital invasion. METHODS: In this consecutive case series, we examined medical records of all patients between 2000 and 2018 with periocular malignancies (other than BCC) invading the anterior orbit (without extraocular muscle or scleral invasion) treated by one orbital surgeon (DP). The main outcome measures included local recurrence, regional and distant metastasis, survival, and visual acuity. RESULTS: Nine patients were identified. Of the non-BCC cancers invading the orbit, squamous cell carcinoma (SCC) (44.4%) was the most prevalent type in our series. Excision included the removal of visibly distinguishable tumor and a free clinical margin of up to 5 mm with histological confirmation of radicality of the invasive tumor component. Reconstruction was achieved by a variety of oculoplastic reconstructive procedures. At a mean follow-up of 70 months (range 11-177 months), 8 out of 9 patients were still alive. Recurrence occurred in two patients with conjunctival melanoma (CM), and they were again treated with wide excision. Postoperative visual acuity remained stable or improved. CONCLUSION: This retrospective case series demonstrates that globe-sparing excisional surgery can be considered in selected cases of periocular malignancies other than BCC with anterior orbital invasion, thus avoiding cosmetic disfigurement and loss of vision due to orbital exenteration.

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INTRODUCTION: Infectious complications after lung resections pose a high burden of perioperative morbidity and mortality. Among other factors, perioperative antibiotic prophylaxis and management of a postoperative pneumonia have an impact on patient outcome. We developed a local clinical pathway for adequate perioperative use of antibiotics. METHODS: We analysed respiratory samples of 200 patients taken before and after lung resection performed in our lung clinic from October 2013 till October 2014. The clinical pathway was based on our local pathogen and resistance pattern as well as on current guidelines and on the principals of antibiotic stewardship. RESULTS: Gram negative bacteria were the predominant pathogens that grew from the samples in the preoperative phase (62%), as well as in the postoperative phase (78%). A significant number of these bacteria showed intrinsic resistance against the commonly used antibiotics for perioperative prophylaxis. This was the case for both the preoperative phase (21%) and the postoperative phase (39%). These findings were integrated into the local clinical pathway. CONCLUSION: The commonly used antibiotics for perioperative prophylaxis in thoracic surgery cover only some of the pathogens responsible for preoperative airway colonisation and postoperative pneumonia. Therefore, perioperative antibiotic prophylaxis should be given as a single shot just before surgery and postoperative pneumonia should be treated as a hospital acquired pneumonia with respect to the local pathogen and resistance pattern.

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Long-term memories are believed to be stored in the synapses of cortical neuronal networks. However, recent experiments report continuous creation and removal of cortical synapses, which raises the question how memories can survive on such a variable substrate. Here, we study the formation and retention of associative memory in a computational model based on Hebbian cell assemblies in the presence of both synaptic and structural plasticity. During rest periods, such as may occur during sleep, the assemblies reactivate spontaneously, reinforcing memories against ongoing synapse removal and replacement. Brief daily reactivations during rest-periods suffice to not only maintain the assemblies, but even strengthen them, and improve pattern completion, consistent with offline memory gains observed experimentally. While the connectivity inside memory representations is strengthened during rest phases, connections in the rest of the network decay and vanish thus reconciling apparently conflicting hypotheses of the influence of sleep on cortical connectivity.

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Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated a high binding capacity of cDMAB and continuous release. Human peripheral mononuclear blood cells (PBMCs) were cultured in the presence of RANKL/MCSF for 28 days and differentiated into osteoclasts. Adding soluble DMAB to the medium inhibited osteoclast differentiation. On nanofunctionalized titanium specimens, the osteoclast-specific TRAP5b protein was monitored and showed a significantly decreased amount on cDMAB-titanium in PBMCs + RANKL/MCSF. PBMCs on cDMAB-titanium also changed SEM cell morphology. In conclusion, the results indicate that cDMAB reduces osteoclast formation and has the potential to reduce osteoclastogenesis on titanium surfaces.

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BACKGROUND: Data on the prevalence of persistent symptoms in the first year after preeclampsia are limited. Furthermore, possible risk factors for these sequelae are poorly defined. We investigated kidney function, blood pressure, proteinuria and urine sediment in women with preeclampsia 6 months after delivery with secondary analysis for possible associated clinical characteristics. METHODS: From January 2007 to July 2014 all women with preeclampsia and 6-months follow up at the University Hospital Basel were analyzed. Preeclampsia was defined as new onset of hypertension (≥140/90 mmHg) and either proteinuria or signs of end-organ dysfunction. Hypertension was defined as a blood pressure ≥ 140/90 mmHg or the use of antihypertensive medication. Proteinuria was defined as a protein-to-creatinine ratio in a spot urine > 11 mg/mmol. Urine sediment was evaluated by a nephrologist. Secondary analyses were performed to investigate for possible parameters associated with persistent symptoms after preeclampsia. RESULTS: Two hundred two women were included into the analysis. At a mean time of follow up of 172 days (+/- 39.6) after delivery, mean blood pressure was 124/76 mmHg (+/- 14/11, range 116-182/63-110) and the mean serum-creatinine was 61.8 µmol/l (33-105 µmol/l) (normal < 110 µmol/l). Mean estimated glomerular filtration rate using CKD-EPI was 110.7 mml/min/1.73m2 (range 59.7-142.4 mml/min/1.73m2) (normal > 60 mml/min/1.73m2). 20.3% (41/202) had a blood pressure of 140/90 mmHg or higher (mean 143/89 mmHg) or were receiving antihypertensive medication (5.5%, 11/202). Proteinuria was present in 33.1% (66/199) (mean 27.5 mg/mmol). Proteinuria and hypertension was present in 8% (16/199). No active urine sediment (e.g. signs of glomerulonephritis) was observed. Age and gestational diabetes were associated with persistent proteinuria and severe preeclampsia with eGFR decline of ≥ 10 ml/min/1.73m2. CONCLUSION: Hypertension and proteinuria are common after 6 months underlining the importance of close follow up to identify those women who need further care.

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Tire road noise is the major contributor to traffic noise, which leads to general annoyance, speech interference, and sleep disturbances. Standardized methods to measure tire road noise are expensive, sophisticated to use, and they cannot be applied comprehensively. This paper presents a method to automatically classify different types of pavement and the wear condition to identify noisy road surfaces. The methods are based on spectra of time series data of the tire cavity sound, acquired under normal vehicle operation. The classifier, an artificial neural network, correctly predicts three pavement types, whereas there are few bidirectional mis-classifications for two pavements, which have similar physical characteristics. The performance measures of the classifier to predict a new or worn out condition are over 94.6%. One could create a digital map with the output of the presented method. On the basis of these digital maps, road segments with a strong impact on tire road noise could be automatically identified. Furthermore, the method can estimate the road macro-texture, which has an impact on the tire road friction especially on wet conditions. Overall, this digital map would have a great benefit for civil engineering departments, road infrastructure operators, and for advanced driver assistance systems.

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Due to their outstanding properties nanodiamonds are a promising nanoscale material in various applications such as microelectronics, polishing, optical monitoring, medicine and biotechnology. Beyond the typical diamond characteristics like extreme hardness or high thermal conductivity, they have additional benefits as intrinsic fluorescence due to lattice defects without photobleaching, obtained during the high pressure high temperature process. Further the carbon surface and its various functional groups in consequence of the synthesis, facilitate additional chemical and biological modification. In this work we present our recent results on chemical modification of the nanodiamond surface with phosphate groups and their electrochemically assisted immobilization on titanium-based materials to increase adhesion at biomaterial surfaces. The starting material is detonation nanodiamond, which exhibits a heterogeneous surface due to the functional groups resulting from the nitrogen-rich explosives and the subsequent purification steps after detonation synthesis. Nanodiamond surfaces are chemically homogenized before proceeding with further functionalization. Suspensions of resulting surface-modified nanodiamonds are applied to the titanium alloy surfaces and the nanodiamonds subsequently fixed by electrochemical immobilization. Titanium and its alloys have been widely used in bone and dental implants for being a metal that is biocompatible with body tissues and able to bind with adjacent bone during healing. In order to improve titanium material properties towards biomedical applications the authors aim to increase adhesion to bone material by incorporating nanodiamonds into the implant surface, namely the anodically grown titanium dioxide layer. Differently functionalized nanodiamonds are characterized by infrared spectroscopy and the modified titanium alloys surfaces by scanning and transmission electron microscopy. The process described shows an adsorption and immobilization of modified nanodiamonds on titanium; where aminosilanized nanodiamonds coupled with O-phosphorylethanolamine show a homogeneous interaction with the titanium substrate.

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Surface functionalization with bioactive molecules (BAMs) on a nanometre scale is a main field in current biomaterial research. The immobilization of a vast number of substances and molecules, ranging from inorganic calcium phosphate phases up to peptides and proteins, has been investigated throughout recent decades. However, in vitro and in vivo results are heterogeneous. This may be at least partially attributed to the limits of the applied immobilization methods. Therefore, this paper highlights, in the first part, advantages and limits of the currently applied methods for the biological nano-functionalization of titanium-based biomaterial surfaces. The second part describes a new immobilization system recently developed in our groups. It uses the nanomechanical fixation of at least partially single-stranded nucleic acids (NAs) into an anodic titanium oxide layer as an immobilization principle and their hybridization ability for the functionalization of the surface with BAMs conjugated to the respective complementary NA strands.

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A new concept for modular biosurface engineering of titanium implants based on the self-assembly of complementary oligonucleotides was biochemically investigated and optimized. This study describes the synthesis and characterization (RP-HPLC and Sakaguchi assay) of oligodeoxyribonucleotide (ODN) conjugates of the hexapeptide GRGDSP containing the RGD sequence as the recognition motif for cellular adhesion receptors (integrins). The peptide was chosen exemplarily as a model molecule, because it is a simple but potent bioactive molecule and relatively well investigated. The conjugation products must fulfill two main requirements: (I) the ability to hybridize and (II) the preservation of biological activity of the RGD peptide for the enhancement of osteoblast adhesion. In the following text, the term "hybridization" is generally used for Watson-Crick base pairing. The ability of the conjugates to hybridize to surface-immobilized complementary ODN was verified by competitive hybridization with radiolabeled ((32)P) complementary strands and by hybridization experiments using a quartz crystal microbalance (QCM). Surface hybridization was further characterized using different adsorption isotherms (e.g., Freundlich and Frumkin types), since the type of isotherm and the derived thermodynamic parameters may reveal characteristic differences between ODN and conjugates thereof. Biological activity of the conjugates was examined in vitro with osteoblasts. The cells were either cultured directly on the ODN-GRGDSP modified titanium implants or used for competition adhesion studies with dissolved ODN-GRGDSP conjugates. All results support the successful establishment of the new surface modification system. Hybridization of RGD peptide-modified nucleic acids to ODN-modified titanium implant materials is thus a promising method for osteoblast attachment in a modular and self-organizing system on implant surfaces.

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This paper describes the immobilization of bioactive molecules on titanium based surfaces through a combination of nano-mechanical fixation of nucleic acid anchor strands (ASs) by partial and regioselective incorporation within an anodic oxide layer and their hybridization with complementary strands (CSs) intended to be conjugated to bioactive molecules. We focus on the interaction between the substrate surface and the anchor strands, the integrity of ASs and their hybridization ability. The observed dependence of adsorption on pH suggests that initial interaction of terminally phosphorylated ASs with the substrate surface is mediated by electrostatic interaction. Using ASs labelled with (32)P at different termini, it could be shown that strand breaks occur, which are attributed (i) to the formation of reactive oxygen species during anodic polarization, (ii) the photocatalytic activity of the titanium oxide and (iii) drying effects. Damage to AS could be considerably reduced if the electrolyte contained 5 mol l(-1) ethanol, light was excluded during the experimental procedure, and the number of drying and rewetting steps was minimized. A total surface density of AS of 4.5 pmol cm(-2) was reached and could be hybridized to CS with an efficiency of up to 100%. A non-complementary strand (NS) bound with less than 0.5% of the amount of CS under similar conditions. Therefore, non-specific binding of CS is considered as negligible.

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PURPOSE OF REVIEW: This review summarises some of the notable papers on ventilator-associated pneumonia (VAP) from January 2003 to October 2004. RECENT FINDINGS: Ventilator-associated pneumonia remains an important drain on hospital resources. All population groups are affected, but patients with VAP are more likely to be older, sicker, and male, with invasive medical devices in situ. Early VAP diagnosis is desirable to reduce VAP mortality and to retard emergence of multidrug-resistant microbes. This may be possible using preliminary culture results or intracellular organism in polymorphonuclear cells. In most intensive care units, Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii are the commonest organisms isolated in VAP. However, causative organisms vary between and within hospitals. Consequently, individual intensive care units should develop empirical antibiotic policies to target the pathogenic bacteria prevalent in their patient populations. Preventative strategies aimed at reducing aerodigestive tract colonisation by pathogenic organisms, and also their subsequent aspiration, are becoming increasingly important. Educating medical staff about these simple measures is therefore pertinent. To reduce the occurrence of multidrug-resistant organisms, limiting the duration of antibiotic treatment to 8 days and antimicrobial rotation should be contemplated. Empirical therapy with antipseudomonal penicillins plus beta-lactamase inhibitors should be considered. If methicillin-resistant Staphylococcus aureus VAP is a possibility, linezolid may be better than vancomycin. SUMMARY: Prevention remains the key to reducing VAP prevalence.

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