Long-term memory consolidation of new words in children with self-limited epilepsy with centro-temporal spikes.

Accelerated long-term forgetting has been studied and demonstrated in adults with epilepsy. In contrast, the question of long-term consolidation (delays > 1 day) in children with epilepsy shows conflicting results. However, childhood is a period of life in which the encoding and long-term storage of new words is essential for the development of knowledge and learning. The aim of this study was therefore to investigate long-term memory consolidation skills in children with self-limited epilepsy with centro-temporal spikes (SeLECTS), using a paradigm exploring new words encoding skills and their long-term consolidation over one-week delay. As lexical knowledge, working memory skills and executive/attentional skills has been shown to contribute to long-term memory/new word learning, we added standardized measures of oral language and executive/attentional functions to explore the involvement of these cognitive skills in new word encoding and consolidation. The results showed that children with SeLECTS needed more repetitions to encode new words, struggled to encode the phonological forms of words, and when they finally reached the level of the typically developing children, they retained what they had learned, but didn't show improved recall skills after a one-week delay, unlike the control participants. Lexical knowledge, verbal working memory skills and phonological skills contributed to encoding and/or recall abilities, and interference sensitivity appeared to be associated with the number of phonological errors during the pseudoword encoding phase. These results are consistent with the functional model linking working memory, phonology and vocabulary in a fronto-temporo-parietal network. As SeLECTS involves perisylvian dysfunction, the associations between impaired sequence storage (phonological working memory), phonological representation storage and new word learning are not surprising. This dual impairment in both encoding and long-term consolidation may result in large learning gap between children with and without epilepsy. Whether these results indicate differences in the sleep-induced benefits required for long-term consolidation or differences in the benefits of retrieval practice between the epilepsy group and healthy children remains open. As lexical development is associated with academic achievement and comprehension, the impact of such deficits in learning new words is certainly detrimental.

Characterising the social interaction style of autism in young adult males with fragile X syndrome.

BACKGROUND: The characterisation of autism in fragile X syndrome (FXS) has been a source of controversy due to the complexity of disentangling autism traits from common features of the FXS phenotype. Autism in FXS is significantly underdiagnosed in the community, which may be partly due to insufficient clinical description of the social interaction profile of autism within the FXS phenotype. In this study, we applied a classic framework for characterising social interaction styles in autism to a sample of young adult males with FXS and co-occurring autism to enhance understanding of how the social challenges associated with autism manifest within FXS. METHODS: Participants were 41 males (M age = 18 years) with FXS and co-occurring autism. Interaction samples were coded for expression of predominately 'active' (characterised by a desire to make social approaches) or 'passive' (characterised by lack of initiation of social approach towards others) interaction profiles. Differences in the expression of phenotypic features of FXS, including anxiety, attention-deficit/hyperactivity disorder, cognitive, adaptive and language impairments and autism symptom severity, were examined across those with passive and active interaction styles. RESULTS: Approximately half of the sample was classified as active and half as passive, demonstrating diversity in the social phenotype of autism associated with FXS. The two subtypes did not differ in autism severity, anxiety or attention-deficit/hyperactivity disorder symptoms or in cognitive, adaptive or language abilities. CONCLUSIONS: This study enhances understanding of FXS-associated autism by documenting phenotypic variability in the social interaction profile in this group, with active and passive social interaction styles represented. The two social interaction styles were not associated with differential expression of common phenotypic features of FXS, suggesting similar support needs.

Evaluation of the better operative outcome software tool to predict cataract surgical outcome in the early postoperative follow-up.

BACKGROUND: Cataracts are the world's leading cause of avoidable blindness. In low-income countries, there are high rates of poor follow-up, which makes it very difficult to monitor surgical outcomes. To address this issue, the Better Operative Outcome Software Tool (BOOST Cataract app) predicts outcome on the first postoperative day and provides specific advice to improve outcomes. The aim of the study is to evaluate the ability of the BOOST Cataract app to categorise surgical outcomes and to analyse the possible factors that contribute to its performance. This was a prospective observational study performed at the General Hospital of Hospitalet of Llobregat. RESULTS: A total of 126 cataracts were included. Patients had a mean [SD] age of 75.8 [12.19] years, and 52% were females. Manual small-incision cataract surgery was involved in 57% and phacoemulsification in 43%. Thirty-eight percent of eyes presented significant corneal oedema on day 1. The BOOST Cataract app succeeded in categorising the final outcome in 65.6% of the eyes and in 93,4% of the eyes with good outcome.The agreement between the BOOST and UDVA outcomes was 0.353 (p< .000). The level of agreement improved to 0.619 (p< .000) in eyes with clear corneas. Success obtained by BOOST for both types of surgery was not statistically different. Eyes that obtained a good outcome on day one after surgery and eyes with clear cornea had 37 times higher odds (95% CI 6.66, 212.83) and 12 times higher odds (95% CI 3.13, 47.66) of being correctly categorised by the BOOST Cataract app than eyes that obtained a suboptimal (moderate and poor) outcome and eyes with corneal oedema on day 1. CONCLUSIONS: The BOOST Cataract app is an e-Health tool designed to address issues of measuring quality in low- and middle-income settings. Although its reliability is limited to eyes that obtain a good outcome and with clear corneas on day 1, the use of the tool on a regular basis facilitates monitoring and reporting outcomes when clinical data collection is challenging due to low postoperative follow-up rates.

Proximal caries infiltration - Pragmatic RCT with 4 years of follow-up.

OBJECTIVES: Efficacy of proximal caries infiltration to arrest lesion progression has been shown in university settings, but only once in a practice-based pragmatic design with a follow-up of 18 months. The aim of this randomized split-mouth placebo-controlled study was to follow-up this cohort for 3 years and those with high caries risk for 4 years. METHODS: Originally, in 87 children and young adults pairs of 238 proximal caries lesions, radiographically extending into inner half of enamel (E2) or outer third of dentin (D1), were randomly allocated to two groups: infiltration (Icon; DMG) or mock (control) treatment by five dentists in four private practices. All subjects received risk-related instructions for diet, flossing and fluoridation. The primary outcome was radiographic lesion progression (pairwise comparison) evaluated by two evaluators independently being blinded to treatment allocation. RESULTS: After 36 months [mean (SD): 1152 (166) days] 165 lesion pairs in 64 patients as well as after 48 months [mean (SD): 1496 (121) days] 71 lesion pairs in 20 high caries risk patients could be re-evaluated clinically as well as radiographically using individualized bitewing holders as at baseline. No adverse events could be observed. After 36 months, progression was recorded in 23/165 test (14%) and 64/165 control lesions (39%) [McNemar/Obuchowski test; p<0.001; relative risk reduction (CI95%): 64 (45-77%)]. After 48 months lesion progression was recorded in 13/71 test (18%) and 34/71 control lesions (48%) [p = 0.003; relative risk reduction (CI95%): 62 (34-78%)] of high caries risk patients. CONCLUSIONS: It can be concluded that also in a practice-setting proximal caries infiltration is more efficacious in reducing lesion progression compared with individualized non-invasive measures alone over a period of four years.

Transscleral Optical Phase Imaging of the Human Retina.

In-vivo observation of the human retina at the cellular level is crucial to detect the first signs of retinal diseases and properly treat them. Despite the phenomenal advances in adaptive optics (AO) systems, clinical imaging of many retinal cells is still elusive due to the low signal-to-noise ratio induced by transpupillary illumination. We present a transscleral optical phase imaging (TOPI) method, which relies on high-angle oblique illumination of the retina, combined with AO, to enhance cell contrast. Examination of eleven healthy volunteer eyes, without pupil dilation, shows the ability of this method to produce in-vivo images of retinal cells, from the retinal pigment epithelium to the nerve fibre layer. This method also allows the generation of high-resolution label-free ex-vivo phase images of flat-mounted retinas. The 4.4°x 4.4° field-of-view in-vivo images are recorded in less than 10 seconds, opening new avenues in the exploration of healthy and diseased retinas.

Infective endocarditis in patients who have undergone transcatheter aortic valve implantation: a review.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been approved for the treatment of severe aortic stenosis since 2008 and recent trials have shown that TAVI is at least non-inferior to surgical aortic valve replacement (SAVR) with regards to short-term efficacy and safety in patients across all surgical risk profiles. Prosthetic valve endocarditis of the transcatheter heart valve is a feared complication; data on the risk of infective endocarditis (IE) subsequent to TAVI are now gradually emerging. OBJECTIVES: We set forth to conduct a review of the incidence, diagnosis, microbial aetiologies, prevention, outcome and management of TAVI-IE. SOURCES: From the MEDLINE database we included a total of 12 observational studies and five studies of long-term results from randomized controlled trials. CONTENT: The incidence of TAVI-IE was reported to be between 0.7% and 3.0% per person-year. The most common microbes were reported to be enterococci, Staphylococcus aureus, streptococci and coagulase-negative staphylococci. International guidelines on prevention strategies of IE recommend good sanitary conditions including cutaneous care, good oral hygiene and good care of dialysis catheters. Antibiotic prophylaxis is recommended by guidelines prior to dental procedures in patients with TAVI; however, evidence is sparse. The majority of the patients included in this review with TAVI-IE had an indication for surgical intervention due to IE (50.0% or more); however, only a small subset of the patients underwent surgery (16.4% or less). The in-hospital mortality was around 25%, i.e. of the same order of magnitude as in prosthetic valve IE in general, but varied substantially between studies (from 11% to 64%). IMPLICATIONS: The US Food and Drug Administration's approval of TAVI in patients at low surgical risk may change the characteristics of patients with TAVI, which may influence the incidence, management, and outcome of patients with TAVI-IE.

Improving antibiotic treatment of bacterial biofilm by hyperbaric oxygen therapy: Not just hot air.

Bacteria and fungi show substantial increased recalcitrance when growing as infectious biofilms. Chronic infections caused by biofilm growing microorganisms is considered a major problem of modern medicine. New strategies are needed to improve antibiotic treatment of biofilms. We have improved antibiotic treatment of bacterial biofilms by reviving the dormant bacteria and thereby make them susceptible to antibiotics by means of reoxygenation. Here we review the rationale for associating lack of oxygen with low susceptibility in infectious biofilm, and how hyperbaric oxygen therapy may result in reoxygenation leading to enhanced bactericidal activity of antibiotics. We address issues of feasibility and potential adverse effects regarding patient safety and development of resistance. Finally, we propose means for supplying reoxygenation to antibiotic treatment of infectious biofilm with the potential to benefit large groups of patients.

A comparative performance analysis of stand-alone, off-grid solar-powered sodium hypochlorite generators.

Sodium hypochlorite (NaClO) is a chemical commodity widely employed as a disinfection agent in water treatment applications. Its production commonly follows electrochemical routes in an undivided reactor. Powering the process with photovoltaic (PV) electricity holds the potential to install stand-alone, independent generators and reduce the NaClO production cost. This study reports the comparative assessment of autonomous, solar-powered sodium hypochlorite generators employing different photovoltaic (PV) technologies: silicon hetero-junction (SHJ) and multi-junction (MJ) solar cells. For Si hetero-junctions, the series connection of either four or five SHJ (4SHJ and 5SHJ, respectively) cells was implemented to obtain the reaction potential required. MJ cells were illuminated by a novel planar solar concentrator that guarantees solar tracking with minimal linear displacements. The three solar-hypochlorite generators were tested under real atmospheric conditions, demonstrating solar-to-chemical conversion efficiencies (SCE) of 9.8% for 4SHJ, 14.2% for 5SHJ and 25.1% for MJ solar cells, respectively. Simulations based on weather databases allowed us to assess efficiencies throughout the entire model year and resulted in specific sodium hypochlorite yearly production rates between 7.2-28 gNaClO cm-2 (referred to the PV surface), depending on the considered PV technology, location, and deployment of electronics converters. The economic viability and competitiveness of solar hypochlorite generators have been investigated and compared with an analog disinfection system deploying ultraviolet lamps. Our study demonstrates the feasibility of off-grid, solar-hypochlorite generators, and points towards the implementation of SHJ solar cells as a reliable technology for stand-alone solar-chemical devices.

Hyperbaric oxygen therapy augments tobramycin efficacy in experimental Staphylococcus aureus endocarditis.

Staphylococcus aureus infective endocarditis (IE) is a serious disease with an in-hospital mortality of up to 40%. Improvements in the effects of antibiotics and host responses could potentially benefit outcomes. Hyperbaric oxygen therapy (HBOT) represents an adjunctive therapeutic option. In this study, the efficacy of HBOT in combination with tobramycin in S. aureus IE was evaluated. A rat model of S. aureus IE mimicking the bacterial load in humans was used. Infected rats treated subcutaneously with tobramycin were randomised into two groups: (i) HBOT twice daily (n = 13); or (ii) normobaric air breathing (non-HBOT) (n = 17). Quantitative bacteriology, cytokine expression, valve vegetation size and clinical status were assessed 4 days post-infection. Adjunctive HBOT reduced the bacterial load in the aortic valves, myocardium and spleen compared with the non-HBOT group (P = 0.004, <0.001 and 0.01, respectively) and improved the clinical score (P <0.0001). Photoplanimetric analysis and weight of valve vegetations showed significantly reduced vegetations in the HBOT group (P <0.001). Key pro-inflammatory cytokines [IL-1ß, IL-6, keratinocyte-derived chemokine (KC) and vascular endothelial growth factor (VEGF)] were significantly reduced in valves from the HBOT group compared with the non-HBOT group. In conclusion, HBOT augmented tobramycin efficacy as assessed by several parameters. These findings suggest the potential use of adjunctive therapy in severe S. aureus IE.

Preservation of the superior rectal artery: influence of surgical technique on anastomotic healing and postoperative morbidity in laparoscopic sigmoidectomy for diverticular disease.

PURPOSE: To evaluate the impact of superior rectal artery (SRA) sparing technique on anastomotic leakage in laparoscopic sigmoidectomy for diverticular disease. MATERIAL AND METHODS: A retrospective multicenter analysis of all patients undergoing laparoscopic sigmoid resection for diverticular disease between 2002 and 2015 was conducted. Data were recorded in three hospitals: University Hospital Regensburg, Marienhospital Gelsenkirchen, and Städtisches Klinikum München Bogenhausen. The SRA was resected between 2002 and 2005. Since 2005, the artery was preserved in most cases. RESULTS: Two hundred sixty-seven patients were included. One hundred sixty patients presented with complicated diverticulitis (60%). The SRA was resected in 102 patients (group 1) and preserved in 157 patients (group 2, no data in eight cases). Anastomotic leakage occurred in 7% of patients in group 1 and 1.9% of patients in group 2 (p = 0.053). Duration of surgery was significantly shorter (157 vs. 183 min, p < 0.001) in group 2 patients. Length of hospital stay was without significant difference (group 1 8.2 days; group 2 8.3 days; p = 0.83). The conversion rate was higher in group 2 patients; however, the difference was not statistically significant (9 vs. 3%, p = 0.07). There was no significant difference between both groups regarding intraoperative complications and overall complication rate. The length of the resected specimen (19 vs. 21 cm, p = 0.001) was significantly shorter in group 2 patients. CONCLUSION: Preservation of the SRA seems to be associated with favorable outcome in patients undergoing laparoscopic sigmoid resection for diverticular disease.

Cleavage of SNAP-25 ameliorates cancer pain in a mouse model of melanoma.

BACKGROUND: Cancer pain is associated with increased pain sensitivity to noxious (hyperalgesia) and normally innocuous (allodynia) stimuli due to activation of nociceptors by tumour-derived mediators or tumour infiltration of nerves. The pain sensitization is accompanied by modifications in gene expression, but specifically regulated genes are largely unknown. The 25 kDa synaptosomal-associated protein (SNAP-25) is involved in chemical neurotransmission at the synaptic cleft. Its inhibition by Botulinum neurotoxin A (BoNT/A) has been associated with antinociceptive effects in migraine, inflammatory and neuropathic pain. However, its potential to reduce tumour-associated pain remains to be clarified. METHODS: We applied a melanoma model of tumour pain in C57BL/6 mice and investigated SNAP-25 expression and regulation by qRT-PCR, Western Blot and immunofluorescence as well as tumour-associated mechanical allodynia with and without BoNT/A treatment. RESULTS: We found increased SNAP-25 expression in the dorsal root ganglia and the sciatic nerve. Intraplantar injection of BoNT/A induced the cleavage of SNAP-25 in these tissues and was associated with decreased mechanical allodynia after therapeutic treatment at early and late stages of tumour pain while the tumour size was not affected. CONCLUSIONS: Our data indicate that SNAP-25 plays a role in tumour pain but has no influence on the initiation and progression of skin cancer. Its cleavage inhibits the development of allodynia in the mouse melanoma model and might be useful as new therapeutic approach for the treatment of cancer pain. WHAT DOES THIS STUDY ADD?: SNAP-25 is differentially regulated during melanoma-induced tumour pain. Its cleavage by BoNT/A might be a suitable therapeutic option for tumour pain patients since tumour-associated pain can be strongly and significantly reduced after preventive and therapeutic BoNT/A treatment, respectively.

Effects of a transdiagnostic unguided Internet intervention ('velibra') for anxiety disorders in primary care: results of a randomized controlled trial.

BACKGROUND: Internet-based cognitive-behavioural treatment (ICBT) for anxiety disorders has shown some promise, but no study has yet examined unguided ICBT in primary care. This randomized controlled trial (RCT) investigated whether a transdiagnostic, unguided ICBT programme for anxiety disorders is effective in primary care settings, after a face-to-face consultation with a physician (MD). We hypothesized that care as usual (CAU) plus unguided ICBT would be superior to CAU in reducing anxiety and related symptoms among patients with social anxiety disorder (SAD), panic disorder with or without agoraphobia (PDA) and/or generalized anxiety disorder (GAD). METHOD: Adults (n = 139) with at least one of these anxiety disorders, as reported by their MD and confirmed by a structured diagnostic interview, were randomized. Unguided ICBT was provided by a novel transdiagnostic ICBT programme ('velibra'). Primary outcomes were generic measures, such as anxiety and depression symptom severity, and diagnostic status at post-treatment (9 weeks). Secondary outcomes included anxiety disorder-specific measures, quality of life, treatment adherence, satisfaction, and general psychiatric symptomatology at follow-up (6 months after randomization). RESULTS: CAU plus unguided ICBT was more effective than CAU at post-treatment, with small to medium between-group effect sizes on primary (Cohen's d = 0.41-0.47) and secondary (Cohen's d = 0.16-0.61) outcomes. Treatment gains were maintained at follow-up. In the treatment group, 28.2% of those with a SAD diagnosis, 38.3% with a PDA diagnosis, and 44.8% with a GAD diagnosis at pretreatment no longer fulfilled diagnostic criteria at post-treatment. CONCLUSIONS: The unguided ICBT intervention examined is effective for anxiety disorders when delivered in primary care.

De Novo Construction of Redox Active Proteins.

Relatively simple principles can be used to plan and construct de novo proteins that bind redox cofactors and participate in a range of electron-transfer reactions analogous to those seen in natural oxidoreductase proteins. These designed redox proteins are called maquettes. Hydrophobic/hydrophilic binary patterning of heptad repeats of amino acids linked together in a single-chain self-assemble into 4-alpha-helix bundles. These bundles form a robust and adaptable frame for uncovering the default properties of protein embedded cofactors independent of the complexities introduced by generations of natural selection and allow us to better understand what factors can be exploited by man or nature to manipulate the physical chemical properties of these cofactors. Anchoring of redox cofactors such as hemes, light active tetrapyrroles, FeS clusters, and flavins by His and Cys residues allow cofactors to be placed at positions in which electron-tunneling rates between cofactors within or between proteins can be predicted in advance. The modularity of heptad repeat designs facilitates the construction of electron-transfer chains and novel combinations of redox cofactors and new redox cofactor assisted functions. Developing de novo designs that can support cofactor incorporation upon expression in a cell is needed to support a synthetic biology advance that integrates with natural bioenergetic pathways.

Whole genome sequencing as a tool for phylogenetic analysis of clinical strains of Mitis group streptococci.

Identification of Mitis group streptococci (MGS) to the species level is challenging for routine microbiology laboratories. Correct identification is crucial for the diagnosis of infective endocarditis, identification of treatment failure, and/or infection relapse. Eighty MGS from Danish patients with infective endocarditis were whole genome sequenced. We compared the phylogenetic analyses based on single genes (recA, sodA, gdh), multigene (MLSA), SNPs, and core-genome sequences. The six phylogenetic analyses generally showed a similar pattern of six monophyletic clusters, though a few differences were observed in single gene analyses. Species identification based on single gene analysis showed their limitations when more strains were included. In contrast, analyses incorporating more sequence data, like MLSA, SNPs and core-genome analyses, provided more distinct clustering. The core-genome tree showed the most distinct clustering.

The phagocytic fitness of leucopatches may impact the healing of chronic wounds.

Chronic non-healing wounds are significantly bothersome to patients and can result in severe complications. In addition, they are increasing in numbers, and a challenging problem to the health-care system. Handling of chronic, non-healing wounds can be discouraging due to lack of improvement, and a recent explanation can be the involvement of biofilm infections in the pathogenesis of non-healing wounds. Therefore, new treatment alternatives to improve outcome are continuously sought-after. Autologous leucopatches are such a new, adjunctive treatment option, showing promising clinical effects. However, the beneficial effect of the patches are not understood fully, although a major contribution is believed to be from the release of stimulating growth factors from activated thrombocytes within the leucopatch. Because the leucopatches also contain substantial numbers of leucocytes, the aim of the present study was to investigate the activity of the polymorphonuclear neutrophils (PMNs) within the leucopatch. By means of burst assay, phagocytosis assay, migration assay, biofilm killing assay and fluorescence in-situ hybridization (FISH) assay we showed significant respiratory burst in PMNs, active phagocytosis and killing of Pseudomonas aeruginosa by the leucopatch. In addition, bacterial-induced migration of PMNs from the leucopatch was shown, as well as uptake of P. aeruginosa by PMNs within the leucopatch. The present study substantiated that at least part of the beneficial clinical effect in chronic wounds by leucopatches is attributed to the activity of the PMNs in the leucopatch.

Anti-Pseudomonas aeruginosa IgY antibodies augment bacterial clearance in a murine pneumonia model.

BACKGROUND: Oral prophylactic therapy by gargling with pathogen-specific egg yolk immunoglobulins (IgY) may reduce the initial airway colonization with Pseudomonas aeruginosa in cystic fibrosis (CF) patients. IgY antibodies impart passive immunization and we investigated the effects of anti-P. aeruginosa IgY antibodies on bacterial eradication in a murine pneumonia model. METHODS: P. aeruginosa pneumonia was established in Balb/c mice and the effects of prophylactic IgY administration on lung bacteriology, clinical parameters and subsequent inflammation were compared to controls. RESULTS: Prophylactic administration of IgY antibodies targeting P. aeruginosa significantly reduced the bacterial burden by 2-log 24h post-infection compared to controls and was accompanied by significantly reduced clinical symptom scores and successive inflammatory cytokine profile indicative of diminished lung inflammation. CONCLUSIONS: Passive immunization by anti-P. aeruginosa IgY therapy facilitates promptly bacterial clearance and moderates inflammation in P. aeruginosa lung infection and may serve as an adjunct to antibiotics in reducing early colonization.

Low efficacy of tobramycin in experimental Staphylococcus aureus endocarditis.

The empiric treatment of infective endocarditis (IE) varies widely and, in some places, a regimen of penicillin in combination with an aminoglycoside is administered. The increasing incidence of Staphylococcus aureus IE, poor tissue penetration by aminoglycosides and low frequency of penicillin-susceptible S. aureus may potentially lead to functional tobramycin monotherapy. Therefore, this study aimed to evaluate tobramycin monotherapy in an experimental S. aureus IE rat model. Catheter-induced IE at the aortic valves were established with S. aureus (NCTC 8325-4) and rats were randomised into untreated (n = 22) or tobramycin-treated (n = 13) groups. The treatment group received tobramycin once-daily. Animals were evaluated at 1 day post infection (DPI), 2 DPI or 3 DPI. Quantitative bacteriology and cytokine expression were measured for valves, myocardium and serum. A decrease of bacterial load was observed in valves and the spleens of the treated (n = 6) compared to the untreated group at 2 DPI (n = 8) (p ≤ 0.02 and p ≤ 0.01, respectively), but not at 3 DPI (n = 7). Quantitative bacteriology in the myocardium was not different between the groups. Keratinocyte-derived chemokine (KC) in the aortic valves was significantly reduced at 2 DPI in the tobramycin-treated group (p ≤ 0.03). However, the expression of interleukin (IL)-1b, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the valves was not different between the two groups. In the myocardium, a significant reduction in IL-1b was observed at 2 DPI (p ≤ 0.001) but not at 3 DPI. Tobramycin as functional monotherapy only reduced bacterial load and inflammation transiently, and was insufficient in most cases of S. aureus IE.

Anti-Pseudomonas aeruginosa IgY Antibodies Induce Specific Bacterial Aggregation and Internalization in Human Polymorphonuclear Neutrophils.

Polymorphonuclear neutrophils (PMNs) are essential cellular constituents in the innate host response, and their recruitment to the lungs and subsequent ubiquitous phagocytosis controls primary respiratory infection. Cystic fibrosis pulmonary disease is characterized by progressive pulmonary decline governed by a persistent, exaggerated inflammatory response dominated by PMNs. The principal contributor is chronic Pseudomonas aeruginosa biofilm infection, which attracts and activates PMNs and thereby is responsible for the continuing inflammation. Strategies to prevent initial airway colonization with P. aeruginosa by augmenting the phagocytic competence of PMNs may postpone the deteriorating chronic biofilm infection. Anti-P. aeruginosa IgY antibodies significantly increase the PMN-mediated respiratory burst and subsequent bacterial killing of P. aeruginosa in vitro. The mode of action is attributed to IgY-facilitated formation of immobilized bacteria in aggregates, as visualized by fluorescence microscopy and the induction of increased bacterial hydrophobicity. Thus, the present study demonstrates that avian egg yolk immunoglobulins (IgY) targeting P. aeruginosa modify bacterial fitness, which enhances bacterial killing by PMN-mediated phagocytosis and thereby may facilitate a rapid bacterial clearance in airways of people with cystic fibrosis.

Vapor-fed microfluidic hydrogen generator.

Water-splitting devices that operate with humid air feeds are an attractive alternative for hydrogen production as the required water input can be obtained directly from ambient air. This article presents a novel proof-of-concept microfluidic platform that makes use of polymeric ion conductor (Nafion®) thin films to absorb water from air and performs the electrochemical water-splitting process. Modelling and experimental tools are used to demonstrate that these microstructured devices can achieve the delicate balance between water, gas, and ionic transport processes required for vapor-fed devices to operate continuously and at steady state, at current densities above 3 mA cm(-2). The results presented here show that factors such as the thickness of the Nafion films covering the electrodes, convection of air streams, and water content of the ionomer can significantly affect the device performance. The insights presented in this work provide important guidelines for the material requirements and device designs that can be used to create practical electrochemical hydrogen generators that work directly under ambient air.

mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma.

BACKGROUND: Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models. METHODS: Human and murine HCC cells, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), hepatic stellate cells (HSCs), human HCC samples, FGFR inhibitor BGJ398 and mammalian target of rapamycin (mTOR) inhibitor rapamycin were used. Effects on growth, motility, signalling and angiogenic markers were determined. In vivo subcutaneous and syngeneic orthotopic tumour models were used. RESULTS: In tumour cells and ECs, targeting FGFR showed significant inhibitory effects on signalling and motility. Minor effects of FGFR inhibition were observed on VSMCs and HSCs, which were significantly enhanced by combining FGFR and mTOR blockade. In vivo daily (5 mg kg(-1)) treatment with BGJ398 led to a significant growth inhibition in subcutaneous tumour models, but only a combination of FGFR and mTOR blockade impaired tumour growth in the orthotopic model. This was paralleled by reduced tumour cell proliferation, vascularisation, pericytes and increased apoptosis. CONCLUSIONS: Targeting FGFR with BGJ398 affects tumour cells and ECs, whereas only a combination with mTOR inhibition impairs recruitment of VSMCs and HSCs. Therefore, this study provides evidence for combined FGFR/mTOR inhibition in HCC.