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Background The aim was to explore patients’ experiences of information and their information needs after discharge for colorectal cancer surgery. Methods Thirty one interviews were performed with sixteen patients during the first seven weeks at home after discharge. Patients were included from three hospitals in the south of Sweden, two of which used an enhanced recovery programme. Results Trying to regain control in life by using information was the overall theme emerging from the interviews. Patients experienced the bodily changes after surgery and the emotional impact of the cancer disease, and these combined experiences seriou/sly affected their ability to manage their daily lives. They both needed, and were in search of, information to increase participation in their own cancer trajectory and to facilitate the regaining of some measure of control in their lives. Waiting for different kinds of information increased the anguish and fear in the face of an unknown future. Conclusions This study showed that receiving information was vital when patients tried to regain control in life after colorectal cancer surgery. The information was necessary in order to facilitate and manage the transition from hospital to home, and the need varied between different transitions. Patients needed more information to manage the daily life at home, but also to understand what the cancer disease really meant to them. This suggests a need for patients to participate more actively in the information and the discharge planning.

High density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro-atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk.

The recently completed human trials SUSTAIN and ASSURE (n=499) showed a 55% reduction of major adverse cardiovascular events (MACE) in atherosclerotic patients treated with statins and oral RVX-208 (200 mg/day). RVX-208 increases ApoA-I, the dominant protein of HDL-c, by selectively inhibiting bromodomain extra-terminal proteins (BET) that are epigenetic readers which regulate chromatin function via binding to acetylated histones. Patients given RVX-208 had increased ApoA-I and HDL-c by 10.3% and 7.7%, respectively. Although significant, these increases may account, in part, for lower MACE. Thus, effects of RVX-208 on other biological processes that impacted atherosclerosis were examined. Specifically, biomarkers of vascular inflammation were measured and microarray techniques were used in studying human primary hepatocytes and whole blood. Results in human aortic endothelial cells (HAEC) exposed to RVX-208 showed suppressed VCAM-1 and MCP-1 with an IC50 of 1uM and 10uM, respectively. In U937 macrophages RVX-208 suppressed the pro-inflammatory cytokine IL-6 (IC50 1uM). Primary hepatocytes treated with RVX-208 lead to upregulation of gene sets within processes such as; transcription, translation and chromatin modeling, as previously seen with other BET inhibitors. More importantly RVX-208 down regulated gene sets within the; complement cascade, fibrin clotting, cholesterol and fatty acid synthesis, innate immune system and diabetes mellitus pathways. Any one of these changes, independently or cumulatively, may underlie the observed MACE reduction. Blood treated ex vivo with RVX-208 suppressed gene sets involved in pro-inflammatory signaling of monocytes and neutrophils, monocyte-endothelial cell interactions, extracellular matrix remodeling and Th1/Th2 cell responses. Moreover, RVX-208 affected genes with known roles in atherosclerosis and/or vascular inflammation yielding an overall anti-atherogenic profile. In summary, the orally active selective BET inhibitor RVX-208 significantly lowers MACE in patients with residual CVD risk receiving standard of care therapy including statins. The above results suggest that RVX-208 alters several biological pathways in a cardioprotective manner which may lead to lower MACE.

HDL mimetic peptides hold promise for the treatment of cardio-metabolic diseases. Transient increases in plasma TG and/or safety concerns may limit their therapeutic applications however, particularly in high risk patients with hypertriglyceridemia and diabetes. Presently, we sought to identify peptide structural features responsible for these adverse effects. The single helix peptide ATI-5261 was used as a model, since it forms a class A α-helix like many HDL mimetic peptides and has exceptional secondary structure and solubility. High dose ip injection (300 mg/kg) of ATI-5261 induced muscle toxicity in C57Bl/6 mice vs. vehicle (serum CPK@4 h = 32,314±2359 vs 143±44 IU/L), increased ALT and AST activities (233±10 & 4595±933 vs 26±6 & 84±21 IU/L) and elevated plasma TG (1951±77 vs 37±7 mg/dl). A majority (~90%) of the cytotoxicity and TG increase was eliminated by removing phenylalanine residues from the apolar face of ATI-5261. Similar results were obtained by removing cationic arginine residues from the lipid-water interface. Thus both features were necessary, but each not sufficient, to induce cytotoxicity and TG elevations. Based on this, a peptide (CS6253) was created that was non-toxic (no adverse effect level >500 mg/kg; t1/2 =7.0±0.6 h in rats), retained secondary structure (75±5% α-helicity), high solubility and ability to stimulate ABCA1-dependent cholesterol efflux efficiently (Km=0.80±0.40 vs. 0.86±0.25 μg/ml ATI-5261). In vivo CS6253 was TG neutral, promoted macrophage RCT, and reduced (32%) substantial atherosclerosis in apoE KO mice fed western diet 10 wks (lesion area = 22±4 vs. 15±2% with 30 mg CS6253/kg, ip injection every 48 h for 6 wks, p

Background Oesophagectomy is a major procedure with known side effects and reduced postoperative quality of life (QOL). It has been shown that support of patients in their new life situation is often lacking. Knowledge about how QOL changes over time is fundamental for addressing patient needs and for determining the optimal timing of supportive care. The aim of this study was to identify QOL changes over time as well as factors that may impact patient QOL during the first year after oesophagectomy for cancer. Methods Patients operated on for adenocarcinoma or squamous cell cancer of the oesophagus were included in this study. Seventy-nine patients completed the European Organisation for Research and Treatment of Cancer QOL questionnaires (QLQ-C30 and QLQ-OES18) before and 2, 4, 6, 9, and 12 months after surgery. A general linear model with repeated measurement analysis of variance was used for statistical testing. Results There was a significant QOL nadir at 2 months compared to 12 months after surgery (QLQ-C30 function scales p < 0.001, symptom scales p < 0.001, QLQ-OES18 scales p < 0.001). Treatment with proton-pump inhibitors was associated with enhanced QOL according to QLQ-C30 symptom scales (p = 0.003) and OES-18 scales (p = 0.015), but age, gender and American Society of Anaesthesiologists classification did not significantly impact QOL. Conclusions Patient QOL is severely hampered the first year after oesophagectomy for cancer, with a nadir at 2 months after surgery. Treatment with proton-pump inhibitors improved patient responses to symptom scales. Evidence of severely affected QOL after surgery indicates that these patients need support at an early stage after surgery. These results can be used by healthcare professionals to develop a postoperative supportive-care programme that is timed and better optimised to meet patient needs. Trial registration: EudraCT database 2009-009997-28.

Spider silk is strong and extensible but still biodegradable and well tolerated when implanted, making it the ultimate biomaterial. Shortcomings that arise in replicating spider silk are due to the use of recombinant spider silk proteins (spidroins) that lack native domains, the use of denaturing conditions under purification and spinning and the fact that the understanding of how spiders control silk formation is incomplete. Recent progress has unraveled the molecular mechanisms of the spidroin N- and C-terminal nonrepetitive domains (NTs and CTs) and revealed the pH and ion gradients in spiders' silk glands, clarifying how spidroin solubility is maintained and how silk is formed in a fraction of a second. Protons and CO2, generated by carbonic anhydrase, affect the stability and structures of the NT and CT in different ways. These insights should allow the design of conditions and devices for the spinning of recombinant spidroins into native-like silk.

The recently reported influence of proinsulin C-peptide on insulin prompted us to examine structural features of the C-peptide. Four sets of limited pattern similarities towards inter-chain end regions of insulin were noticed, involving secondary structure elements, binding residues and intra- as well as inter-peptide residue similarities. Using surface plasmon resonance, we examined insulin binding to truncated, soluble insulin receptor A and IGF-1 receptor, but C-peptide effects on these bindings were not detectable. Two forms of the insulin receptor, differing in activation of gene transcription with regards to (pre)proinsulin and glucokinase, respectively, were also uninfluenced by C-peptide. We conclude that the pattern similarities, if functional, reflect C-peptide interactions with molecules other than both insulin A and B receptors and IGF-1 receptors. Any such effects are of interest in relation to reported binding interactions between insulin and C-peptide.

Over a period of 50 years at Kiruna iron ore mine in the far north of Sweden we can see a transformation of work from underground to remote control at surface level. What characterized the old underground workface was the close relation between man and the hard rock centred on arduous physical work under dangerous conditions. Today, the face miners are located ‘up in the sky’ on the seventh level of an office building close to the mine. The workers leave their job at the end of the shift just as clean as when they arrived. The contact with the hard rock is mediated by machines controlled by remote control technology. The modern technology has created a new type of work - new in terms of competencies and knowledge as well as workload. The purpose of this article is to reflect on the technical development of underground mining in Kiruna and to consider the implications it has had on qualifications, identity and gender. There is an emerging, and in many aspects already evident, knowledge transformation - from the old and obsolete physical and tacit knowledge and skills (for example the ability to ‘read the rock’) to something new which can be described as abstract knowledge. But the old culture still provides an important context for workplace learning and the construction of identity and gender. This is associated with a degree of ‘worker identity lag’ and to difficulties in adapting attitudes and norms to the demands and structures that result from the new technology and the new work tasks. The new forms of work in the mine have less need for the traditional mining competencies, attitudes and ideals. The traditional workplace culture and its ‘macho style’ have also been challenged. Workers have to find new ways to learn and to develop a workplace culture more attuned to a new type of worker identity and masculinity.

Spider silk has been extensively studied for its outstanding mechanical properties. Partial intermediate and C-terminal sequences of different spider silk proteins have been determined, and during the past decade also N-terminal domains have been characterized. However, only some of these N-terminal domains have been reported to contain signal peptides, leaving the mechanism whereby they enter the secretory pathway open to speculation. Here we present the sequence of a 394-residue N-terminal region of the Euprosthenops australis major ampullate spidroin 1 (MaSp1). A close comparison with published sequences from other species revealed the presence of N-terminal signal peptides followed by an approximately 130-residue nonrepetitive domain. From secondary structure predictions, helical wheel analysis, and circular dichroism spectroscopy this domain is concluded to contain five alpha-helices and is a conserved constituent of hitherto analyzed dragline, flagelliform, and cylindriform spider silk proteins.

Alzheimer disease is characterized by extracellular plaques composed of Abeta peptides. We show here that these plaques also contain the serine protease inhibitor neuroserpin and that neuroserpin forms a 1:1 binary complex with the N-terminal or middle parts of the Abeta(1-42) peptide. This complex inactivates neuroserpin as an inhibitor of tissue plasminogen activator and blocks the loop-sheet polymerization process that is characteristic of members of the serpin superfamily. In contrast neuroserpin accelerates the aggregation of Abeta(1-42) with the resulting species having an appearance that is distinct from the mature amyloid fibril. Neuroserpin reduces the cytotoxicity of Abeta(1-42) when assessed using standard cell assays, and the interaction has been confirmed in vivo in novel Drosophila models of disease. Taken together, these data show that neuroserpin interacts with Abeta(1-42) to form off-pathway non-toxic oligomers and so protects neurons in Alzheimer disease.

This article reports on a qualitative study of adolescents living in residential care in Sweden. Six adolescents, three girls and three boys, who were the first to live in a newly opened treatment home, were interviewed about their experiences 2–3 years after they had left the home. Their experiences were in retrospect very different from each other. The results are discussed from the perspectives of individual differences, the special situation in an institution, relationships and gender. It is concluded that in spite of the fact that youth who live in a residential care institution live in the same environment, the individuals perceive it in their own unique ways.

Native lung surfactant protein C (SP-C) is a 4.2-kDa acylpeptide that associates with alveolar surfactant phospholipids via a transmembrane alpha-helix. This helix contains mainly Val, although poly-Val is inefficient in helix formation, and helical SP-C can spontaneously convert to beta-sheet aggregates and amyloid-like fibrils. SP-C is cleaved out from a 21-kDa integral membrane protein, proSP-C, in the alveolar type II cell. Recently several mutations localized in the endoplasmic reticulum-lumenal (C-terminal) part of proSP-C (CTproSP-C) have been associated with intracellular accumulation of toxic forms of proSP-C, low levels of mature SP-C, and development of interstitial lung disease. CTproSP-C contains a approximately 100-residue Brichos domain of unknown function that is also found in other membrane proteins associated with amyloid formation, dementia, and cancer. Here we find that recombinant CTproSP-C binds lipid-associated SP-C, which is in beta-strand conformation, and that this interaction results in an increased helical content. In contrast, CTproSP-C does not bind alpha-helical SP-C. Recombinant CTproSP-C(L188Q), a mutation associated with interstitial lung disease, shows secondary and quaternary structures similar to those of wild type CTproSP-C but is unable to bind lipid-associated beta-strand SP-C. Transfection of CTproSP-C into HEK293 cells that express proSP-C(L188Q) increases the amount of proSP-C protein, whereas no effect is seen on cells expressing wild type proSP-C. These findings suggest that CTproSP-C binds nonhelical SP-C and thereby prevents beta-sheet aggregation and that mutations in CTproSP-C can interfere with this function.

The purpose of this study was to use images from a microwave sensor on a pixel level for simultaneous prediction of moisture content and density of wood. The microwave sensor functions as a line-scan camera with a pixel size of 8mm. Boards of Scots pine (Pinus sylvestris), 25 and 50mm thick, were scanned at three different moisture contents. Dry density and moisture content for each pixel were calculated from measurements with a computed tomography scanner. It was possible to create models for prediction of density on a pixel level. Models for prediction of moisture content had to be based on average values over homogeneous regions. Accuracy will be improved if it is possible to make a classification of knots, heartwood, sapwood, etc., and calibrate different models for different types of wood. The limitations of the sensor used are high noise in amplitude measurements and the restriction to one period for phase measurements.

The BRICHOS domain is associated with human amyloid disease, and it efficiently prevents amyloid fibril formation of the amyloid β-peptide (Aβ) in vitro and in vivo. Recombinant human prosurfactant protein C (proSP-C) BRICHOS domain forms a homotrimer as observed by x-ray crystallography, analytical ultracentrifugation, native polyacrylamide gel electrophoresis, analytical size exclusion chromatography and electrospray mass spectrometry. It was hypothesized that the trimer is an inactive storage form, as a putative substrate-binding site identified in the monomer, is buried in the subunit interface of the trimer. We show here increased dissociation of the BRICHOS trimer into monomers, by addition of detergents or of bis-ANS, known to bind to the putative substrate-binding site, or by introducing a Ser to Arg mutation expected to interfere with trimer formation. This leads to increased capacity to delay Aβ42 fibril formation. Cross-linking of the BRICHOS trimer with glutaraldehyde, in contrast, renders it unable to affect Aβ42 fibril formation. Moreover, proSP-C BRICHOS expressed in HEK293 cells is mainly monomeric, as detected by proximity ligation assay. Finally, proteolytic cleavage of BRICHOS in a loop region that is cleaved during proSP-C biosynthesis results in increased capacity to delay Aβ42 fibril formation. These results indicate that modulation of the accessibility of the substrate-binding site is a means to regulate BRICHOS activity.

Proinsulin C-peptide influences a number of physiological parameters in addition to its well-established role in the parent proinsulin molecule. It is of interest as a candidate for future co-replacement therapy with insulin for patients with diabetes mellitus type 1, but specific receptors have not been identified and additional correlation with functional effects is desirable. Based on comparisons of 22 mammalian proinsulin variants, we have constructed analogues for activity studies, choosing phosphorylation of mitogen-activated protein kinases (MAPKs) in Swiss 3T3 fibroblasts for functional measurements. In this manner, we find that effective phosphorylation of MAPKs is promoted by the presence of conserved glutamic acid residues at positions 3, 11 and 27 of C-peptide and by the presence of helix-promoting residues in the N-terminal segment. Previous findings have ascribed functional roles to the C-terminal pentapeptide segment, and all results combined therefore now show the importance of different segments, suggesting that C-peptide interactions are complex or multiple.

To evaluate risk factors for dysplasia and adenocarcinoma development in nondysplastic Barrett mucosa.The risk for patients with Barrett esophagus to develop esophageal adenocarcinoma is low, and most patients undergoing surveillance will not develop malignancy. Identification of risk factors may allow for more rational surveillance programs in which patients are stratified according to their individual risk of progressing to dysplasia and invasive adenocarcinoma.The development of dysplasia and esophageal adenocarcinoma was studied during long-term endoscopic and histologic surveillance in 140 patients with Barrett esophagus free from dysplasia. Risk factors for progression to dysplasia and adenocarcinoma were evaluated.Median follow-up was 5.8 years. Forty-four patients (31.4%) developed low-grade dysplasia and 7 patients (5%) developed high-grade dysplasia or esophageal adenocarcinoma. Dysplasia development was significantly less common after antireflux surgery compared with conventional medical therapy. Low-grade dysplasia (relative risk = 5.5; 95% confidence interval, 1.1-28.6) and long duration of reflux symptoms (relative risk = 1.3; 95% confidence interval, 1.2-1.7) were independently associated with an increased risk of developing high-grade dysplasia or esophageal adenocarcinoma.Successful antireflux surgery protects the Barrett mucosa from developing high-grade dysplasia and esophageal adenocarcinoma, possibly by better control of reflux of gastric contents. Low-grade dysplasia is the only clinically useful risk factor that permits stratification of the surveillance intervals according to the risk of the individual patient.

To study possible social predictors for reduction of hyperlipidaemia in subjects offered lifestyle intervention in primary health care after an opportunistic screening.Primary health care in Sollentuna, Sweden.Follow-up study of changes in high lipid levels in men and women aged 20-60 years participating in a voluntary screening and cardiovascular prevention programme.A total of 1904 individuals had a follow-up visit registered after a mean of 466 days. Men and women with raised lipid levels (serum cholesterol = 6.5 mmol/l, and/or triglycerides = 2.3 mmol/l) at baseline were compared with normolipidaemic participants. Data on social characteristics such as education, occupation, marital status, and income were collected from national censuses. Associations between socioeconomic factors and changes in lipid levels were studied.Men and women with hyperlipidaemia were generally (p0.001) older (men 6-8 years, women 8-10 years) and less educated than normolipidaemic subjects. Significant predictors for reducing hypercholesterolaemia were younger age, OR 0.97 (0.95-1.00) for increasing age, and longer education, OR 0.47 (0.24-0.91) for low education (9 years). Foreign-born subjects were more likely to achieve a high success rate in reducing hypercholesterolaemia, OR 3.43 (1.00-11.8), than the Swedish-born. No significant predictors were detected for reduction of high triglyceride levels.A successful reduction of high cholesterol levels was associated with younger age and longer education in a primary health care-based programme for cardiovascular prevention.

We have used a novel polyelectrolyte multilayer (PEM) coating consisting of the polyelectrolytes collagen and hyaluronic acid. The build-up by the layer-by-layer deposition technique is outlined by ex situ and in situ ellipsometric measurements. When collagen was added, the thickness of the PEM was increased, and the refractive index was decreased. Corresponding but opposite effects were noted when hyaluronic acid was added. These changes are considered to be explained by a diffusion mechanism. It was also found that the PEM layers were unstable at physiological pH. However, by cross-linking using N-(3-di-methylaminopropyl)-N'-ethylcarbodiimide together with N-hydroxysuccinimide, a stable PEM layer resulted. These tissue friendly PEM layers are expected to have a great impact in the design of artificial extracellular matrixes. Also, the insertion of fluorescence labels demonstrates the potential for incorporation of other functionalities.

The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 Å) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel β-sheets in a cross-β arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel β-sheets are zipped together by means of π-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid–lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.

The hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of surface-active lipids to the air-liquid interface of the alveoli and are essential for alveolar stability and gas exchange. Synthetic surfactant preparations must contain at least one of these hydrophobic proteins, or analogs thereof, to have optimal effects when administered into the airways of patients with lung diseases. However, development of clinically active artificial surfactants has turned out to be more complicated than initially anticipated since the native hydrophobic proteins are structurally complex or unstable in pure form. The proteins have been replaced by different analogs which have the right conformation without forming oligomers. Increased understanding of the surfactant proteins will hopefully lead to development of effective synthetic surfactants which can be produced in large quantities for treatment of a wide range of respiratory disorders. Furthermore, the lipid composition seems to be important, as well as a high lipid concentration in the suspension. For successful treatment of many respiratory diseases, it is also desirable that the synthetic surfactant resists inactivation by plasma components leaking into the alveoli.

A new wireless technique for oesophageal pH monitoring has recently been introduced (Bravo). To implement this technique in clinical practice, values of normal oesophageal acid exposure need to be defined in a large age- and gender-matched healthy population. The aims of this study were to investigate the feasibility and safety of the wireless technique and to establish normal values for oesophageal acid exposure.Fifty-seven asymptomatic subjects underwent upper gastrointestinal endoscopy with transoral placement of a radio-transmitting capsule 6 cm above the squamocolumnar junction. Oesophageal acid exposure was monitored via a portable receiver during 48 h.Seven men were excluded from the study: capsule dysfunction in 1 and oesophagitis in 6. Fifty subjects (25 M, 25 F, median age 42 years) were included in the study. The radio-transmitting capsule was successfully attached to the oesophageal mucosa in all cases and there were no complications. During pH monitoring 2 capsules were prematurely detached after 32 and 36 h, respectively. The median percentage time with oesophageal pH of less than 4 was 0.7% on day 1 and 1.0% on day 2 (p = 0.033) and the 95th percentile for the 48-h recordings was 4.4%.Ambulatory pH monitoring using the Bravo system is feasible and appears to be safe. This is the first study to establish normal values for oesophageal acid exposure in a large age- and gender-matched healthy population and offers a basis for the use of the wireless technique in clinical practice.

The dementia familial encephalopathy with neuroserpin inclusion bodies (FENIB) is caused by point mutations in the neuroserpin gene. We have shown a correlation between the predicted effect of the mutation and the number of intracerebral inclusions, and an inverse relationship with the age of onset of disease. Our previous work has shown that the intraneuronal inclusions in FENIB result from the sequential interaction between the reactive centre loop of one neuroserpin molecule with b-sheet A of the next. We show here that neuroserpin Portland (Ser52Arg), which causes a severe form of FENIB, also forms loop-sheet polymers but at a faster rate, in keeping with the more severe clinical phenotype. The Portland mutant has a normal unfolding transition in urea and a normal melting temperature but is inactive as a proteinase inhibitor. This results in part from the reactive loop being in a less accessible conformation to bind to the target enzyme, tissue plasminogen activator. These results, with those of the CD analysis, are in keeping with the reactive centre loop of neuroserpin Portland being partially inserted into b-sheet A to adopt a conformation similar to an intermediate on the polymerization pathway. Our data provide an explanation for the number of inclusions and the severity of dementia in FENIB associated with neuroserpin Portland. Moreover the inactivity of the mutant may result in uncontrolled activity of tissue plasminogen activator, and so explain the epileptic seizures seen in individuals with more severe forms of the disease.

Several proteins and peptides that can convert from alpha-helical to beta-sheet conformation and form amyloid fibrils, including the amyloid beta-peptide (Abeta) and the prion protein, contain a discordant alpha-helix that is composed of residues that strongly favor beta-strand formation. In their native states, 37 of 38 discordant helices are now found to interact with other protein segments or with lipid membranes, but Abeta apparently lacks such interactions. The helical propensity of the Abeta discordant region (K16LVFFAED23) is increased by introducing V18A/F19A/F20A replacements, and this is associated with reduced fibril formation. Addition of the tripeptide KAD or phospho-L-serine likewise increases the alpha-helical content of Abeta(12-28) and reduces aggregation and fibril formation of Abeta(1-40), Abeta(12-28), Abeta(12-24), and Abeta(14-23). In contrast, tripeptides with all-neutral, all-acidic or all-basic side chains, as well as phosphoethanolamine, phosphocholine, and phosphoglycerol have no significant effects on Abeta secondary structure or fibril formation. These data suggest that in free Abeta, the discordant alpha-helix lacks stabilizing interactions (likely as a consequence of proteolytic removal from a membrane-associated precursor protein) and that stabilization of this helix can reduce fibril formation.

Surfactant protein B (SP-B) is an essential constituent of pulmonary surfactant. SP-B is synthesized in alveolar type II cells as a preproprotein and processed to the mature peptide by the cleavage of NH2- and COOH-terminal peptides. An aspartyl protease has been suggested to cleave the NH2-terminal propeptide resulting in a 25-kDa intermediate. Napsin, an aspartyl protease expressed in alveolar type II cells, was detected in fetal lung homogenates as early as day 16 of gestation, 1 day before the onset of SP-B expression and processing. Napsin was localized to multivesicular bodies, the site of SP-B proprotein processing in type II cells. Incubation of SP-B proprotein from type II cells with a crude membrane extract from napsin-transfected cells resulted in enhanced levels of a 25-kDa intermediate. Purified napsin cleaved a recombinant SP-B/EGFP fusion protein within the NH2-terminal propeptide between Leu178 and Pro179, 22 amino acids upstream of the NH2 terminus of mature SP-B. Cathepsin H, a cysteine protease also implicated in pro-SP-B processing, cleaved SP-B/EGFP fusion protein 13 amino acids upstream of the NH2 terminus of mature SP-B. Napsin did not cleave the COOH-terminal peptide, whereas cathepsin H cleaved the boundary between mature SP-B and the COOH-terminal peptide and at several other sites within the COOH-terminal peptide. Knockdown of napsin by small interfering RNA resulted in decreased levels of mature SP-B and mature SP-C in type II cells. These results suggest that napsin, cathepsin H, and at least one other enzyme are involved in maturation of the biologically active SP-B peptide.

Background Reports of esophageal anastomotic complications often involve more gastric than colonic reconstructions and are incomplete because of fragmented followup by physicians unfamiliar with the surgical procedure. Study design Three hundred ninety-three consecutive esophagectomy patients had prevalence and risk factors determined for graft ischemia and anastomotic leak; 363 of these patients followed for more than 1 month (median 15 months) had prevalence and risk factors determined for anastomotic stricture. Results Conduit ischemia occurred in 36 (9.2%) and anastomotic leak in 43 patients (10.9%). Risk factor for ischemia was comorbid conditions requiring therapy (Odds ratio [OR]: 2.2 [95% CI 1.1–4.3]), and for leak were ischemia (OR: 5.5 [95% CI 2.5–12.1]), neoadjuvant therapy (OR: 2.2 [95% CI 1.1–4.5]), and comorbid conditions (OR: 2.1 [95% CI 1.1–3.9]). A stricture developed in 80 patients (22.0%). Risk factors were ischemia (OR: 4.4 [95% CI 2.0–9.6]), anastomotic leak (OR: 3.8 [95% CI 1.9–7.6]), and increasing preoperative weight (p = 0.022). The prevalence of ischemia was similar after gastric (10.4%) versus colonic (7.4%) reconstruction; leak and stricture were more common (14.3% versus 6.1%, p=0.013, 31.3% versus 8.7%, p Conclusions After esophagectomy 10% of patients will develop conduit ischemia or an anastomotic leak and 22% will develop anastomotic stricture. Anastomotic leak and strictures are more common and the strictures are more severe after gastric pull-up compared with colon interposition. Dilatation is a safe and effective treatment.

The formation of amyloid fibrils is associated with several devastating diseases in humans and animals, including e.g. Alzheimer's disease (AD) and the spongiform encephalopathies. Here, we review and discuss the current knowledge on two amyloid peptides: lung surfactant protein C (SP-C) and the amyloid beta-peptide (Abeta), implicated in human lung disease and in AD, respectively. Both these hydrophobic peptides are derived from the transmembrane region of their precursor protein, and can transit from a monomeric alpha-helical state to a beta-sheet fibril. The alpha helices of SP-C and Abeta are composed of amino acid residues with inherently higher propensities for beta strand than helix conformation. Their helical states are stabilized by a membrane environment, and loss of membrane association thus promotes structural conversion and fibril formation. We speculate that the loss of structural context for sequences with a high propensity for formation of beta sheets may be a common feature of amyloid formation in general.

Objective: The purpose of the study was to compare in prospective randomized fashion a manually sutured esophagogastric anastomosis in the neck and a stapled in the chest after esophageal resection and gastric tube reconstruction. Summary Background Data: Despite the fact that all reconstructions after esophagectomy will result in a cervical or a thoracic anastomosis, controversy still exists as to the optimal site for the anastomosis. In uncontrolled studies, both neck and chest anastomoses have been advocated. The only reported randomized study is difficult to evaluate because of varying routes of the substitute and different anastomotic techniques within the groups. The reported high failure rate of stapled anastomoses in the neck and the fact that most surgeons prefer to suture cervical anastomoses made us choose this technique for anastomosis in the neck. Our routine and the preference of most surgeons to staple high thoracic anastomoses became decisive for type of thoracic anastomoses. Methods: Between May 9, 1990 and February 5, 1996, 83 patients undergoing esophageal resection were prospectively randomized to receive an esophagogastric anastomosis in the neck (41 patients) or an esophagogastric anastomosis in the chest (42 patients). To evaluate selection bias, patients undergoing esophageal resection during the same period but not randomized (n = 29) were also followed and compared with those in the study (n = 83). Objective measurements of anastomotic level and diameter were assessed with an endoscope and balloon catheter 3, 6, and 12 months after surgery. The long-term survival rates were compared with the log-rank test. Results: Two patients (1.8%) died in hospital, and the remaining 110 patients were followed until death or for a minimum of 60 months. The genuine 5-year survival rate was 29% for chest anastomoses and 30% for neck anastomoses. The overall leakage rate was 1.8% (2 cases of 112) with no relation to mortality or anastomotic method. All patients in the randomized group had tumor-free proximal and distal resection lines, but 1 patient in the nonrandomized group had tumor infiltrates in the proximal resection margin. At 3, 6, and 12 months after operation, there was no difference in anastomotic diameter between the esophagogastric anastomosis in the neck and in the thorax (P = 0.771), and both increased with time (P = 0.004, ANOVA repeated measures). Body weight development was the same in the two groups. With similar results in randomized and nonrandomized patients, study bias was eliminated. Conclusions: When performed in a standardized way, neck and chest anastomoses after esophageal resection are equally safe. The additional esophageal resection of 5 cm in the neck group did not increase tumor removal and survival; on the other hand, it did not adversely influence morbidity, anastomotic diameter, or eating as reflected by body weight development. (Less)

Non-destructive testing of wood for prediction of strength is significantly influenced by wood density and moisture content. A sensor capable of measuring both density and moisture content would be a good tool to aid in predicting the strength of sawn timber. This study was carried out to investigate the possibility of calibrating a prediction model for the moisture content and density of Scots pine (Pinus sylvestris) using microwave sensors. The material was initially at green moisture content, and thereafter dried in several steps to zero moisture content. At each step all the samples were weighted, scanned with a microwave camera (Satimo 9.4 GHz) and CT scanned with a medical CT scanner (Siemens Somatom AR.T.). The output variables from the microwave camera were used as predictors, and CT images correlated with known moisture content were used as response variables. Multivariate models to predict moisture content and density were calibrated using partial least squares (PLS) regression. The result shows that it is possible to predict both moisture content and density with very high accuracy using microwave sensors.

This study was carried out to investigate the possibility of calibrating a prediction model for the moisture content and density distribution of Scots pine (Pinus sylvestris) using microwave sensors. The material was initially of green moisture content and was thereafter dried in several steps to zero moisture content. At each step, all the pieces were weighed, scanned with a microwave sensor (Satimo 9,4 GHz), and computed tomography (CT)-scanned with a medical CT scanner (Siemens Somatom AR.T.). The output variables from the microwave sensor were used as predictors, and CT images that correlated with known moisture content were used as response variables. Multivariate models to predict average moisture content and density were calibrated using the partial least squares (PLS) regression. The models for average moisture content and density were applied at the pixel level, and the distribution was visualized. The results show that it is possible to predict both moisture content distribution and density distribution with high accuracy using microwave sensors.

Background The objectives of this study were to determine the influence of glucose control on lipoprotein and haemostasis variables in Type 1 diabetes mellitus patients and to evaluate the global impact of these metabolic risk factors on brachial artery reactivity and carotid artery atherosclerosis, stiffness and diameter. Design Follow up of Type 1 diabetes patients randomized to insulin-intensive conventional treatment (ICT, n = 29) or insulin-standard treatment (ST, n = 25) in the Stockholm Diabetes Intervention Study (SDIS) more than 14 years ago. Results The intensive conventional treatment patients had lower glycosylated haemoglobin (HbA1c) compared with the ST patients, i.e. 7·01 (SD 0·51) vs. 8·31 (0·97), while concentrations of the lipoprotein and haemostasis variables analyzed were virtually similar. The carotid artery intima-media area was associated with high HbA1c, high serum (S)-cholesterol levels, and low high-density lipoprotein (HDL)-cholesterol levels. Carotid artery stiffness was associated with high systolic blood pressure, high HbA1c, high fibrinogen, and high HDL-cholesterol. Brachial artery endothelial reactivity was higher for women and those with low S-cholesterol. Conclusion In patients with Type 1 diabetes, glucose control appeared to have no effect on either lipoproteins or haemostasis variable concentrations. Poor glucose control, and high levels of S-cholesterol, systolic blood pressure and plasma fibrinogen were associated with development of atherosclerosis, thus emphasising the importance of global risk factor control in patients with Type 1 diabetes mellitus.

Background— We have previously demonstrated vasculoprotective effects after repeated intravenous administration of recombinant apolipoprotein A-I Milano (apoA-I m )/phospholipid complex. In this study, we sought to determine the effects of local recombinant apoA-I m /1-palmitoyl,2-oleoyl phosphatidylcholine complex (ETC-216) delivered intramurally via the Infiltrator catheter on luminal narrowing in a porcine coronary artery stent overstretch injury model. Methods and Results— In twelve domestic swine (≈25 kg), two arteries each were infiltrated with 0.4 mL ETC-216 (14 mg/mL) or vehicle control immediately before deployment of GFX stents (stent:artery ratio=1.3:1). Animals were euthanized at day 28, and evaluation by QCA revealed a significant improvement in mean lumen loss index with ETC-216 treatment (21±22% versus 43±13% lumen loss; P =0.01). Histomorphometric analysis showed that ETC-216 treatment significantly reduced the intimal area (6.7±1.5 versus 5.2±1.4 mm 2 , −22%; P =0.02) and the stenosis index (0.76±0.15 versus 0.59±0.15; P =0.01), and increased the lumen area (2.1±1.4 versus 3.7±1.8 mm 2 , +76%; P =0.02). Regression analysis showed significant differences in lumen area ( P =0.004), neointimal area ( P =0.003), stenosis index ( P =0.001), and neointimal thickness ( P =0.003) adjusted for injury score in favor of ETC-216. Conclusions— A single intramural administration of ETC-216 significantly inhibited injury-induced luminal narrowing in the porcine stent overstretch model through reduction of intimal hyperplasia. These data show that local intracoronary delivery of ETC-216 may be useful to prevent restenosis after coronary stenting.

This article considers an ongoing research project concerning the outcome of the Swedish reform of advanced vocational education (AVE) from a graduate perspective. Launched in 1996 as an experimental post-secondary reform meeting the advancements within working life, several new educational features were introduced. In January 2002, AVE became a regular part of the national education system with 12,500 education places per annum. From start to present, over 6,100 students have graduated from the approximately 350 different national AVE programmes available. The purpose of this article is to present results from three sets of questionnaires collected in 1999, 2000 and 2001 surveying over 5,400 of the graduates concerning their opinions and experiences on how AVE corresponds to the demands and requests made of them when entering the labour market. The aggregate results suggest that a majority of the graduates (82%) had a job 6 months after having completed their AVE programmes and that approximately 80% of them were working, with regard to their educational focus, within a ‘target’ field of profession.

Based on the findings that proinsulin C-peptide binds specifically to cell membranes, we investigated the effects of C-peptide and related molecules on the intracellular Ca2+ concentration ([Ca2+]i) in human renal tubular cells using the indicator fura-2/AM. The results show that human C-peptide and its C-terminal pentapeptide (positions 27-31, EGSLQ), but not the des (27-31) C-peptide or randomly scrambled C-peptide, elicit a transient increase in [Ca2+]i. Rat C-peptide and rat C-terminal pentapeptide also induce a [Ca2+]i response in human tubular cells, while a human pentapeptide analogue with Ala at position 1 gives no [Ca2+]i response, and those with Ala at positions 2-5 induce responses with different amplitudes. These results define a species cross-reactivity for C-peptide and demonstrate the importance of Glu at position 1 of the pentapeptide. Preincubation of cells with pertussis toxin abolishes the effect on [Ca2+]i by both C-peptide and the pentapeptide. These results are compatible with previous data on C-peptide binding to cells and activation of Na-,K+ATPase. Combined, all data show that C-peptide is a bioactive peptide and suggest that it elicits changes in [Ca2+]i via G-protein-coupled pathways, giving downstream enzyme effects.

The objective of the present study was to test for multigroup invariance in measurement models and structural models between job characteristics, psychosocial intervening variables, health outcomes and sickness absenteeism. Four types of occupation were represented in the study: blue-collar workers ( n = 241), white-collar workers ( n = 209), elderly-care workers ( n = 338) and child-care workers ( n = 336). A first-order, six-factor multigroup confirmatory factor analysis model (i.e. measurement model) composed of two perceived job characteristics ( job autonomy and skill discretion), appraised workload, job satisfaction, stress-related ill-health and sickness absenteeism provided a good model fit. Invariance tests showed that the six-factor model fits well for all occupations. A partially recursive mediated multigroup structural model showed both similarities and differences across occupations as regards the relationships between independent latent variables ( job autonomy, skill discretion), intervenin...

This investigation of white-collar workers ( n = 201) in Swedish industrial environments focused on an empirical examination of the relationships between work with visual display units (VDUs), psychosocial factors (skill discretion, appraised work load, job satisfaction), physical work load and musculoskeletal shoulder symptoms. This cross-sectional study was based upon questionnaire surveys carried out at industrial companies. The prevalence of shoulder symptoms during the previous year was 39%. Nearly one-half of the participants reported that they used a VDU for at least 4 h/day ('high VDU use'). High VDU use was related to increased Prevalence Odds Ratio (POR) for shoulder symptoms. After adjustment for physical work load, significant PORs were found in groups with high VDU use in combination with low job satisfaction (POR = 4.8) or high appraised work load (POR = 3.5), compared to groups with low VDU use in combination with high job satisfaction or low work load (reference groups).

In the respiratory tract, recognition of bacterial endotoxin (lipopolysacharide, LPS) is a critical step of the innate host defense system directed against invading pathogens. Secretions of the airways contain proteins that have direct antimicrobial activity (lysozyme, lactoferrin, defensins, and cathelicidins) as well as complement factors and surfactant proteins that contribute to host defense. The hydrophobic surfactant protein C (SP-C) recognizes LPS (Augusto, L., Le Blay, K., Auger, G., Blanot, D., and Chaby, R. (2001) Am. J. Physiol. 281, L776-L785). In the present study, using synthetic analogs of SP-C, we demonstrate that the palmitoyl residues of SP-C are not required for the interaction with LPS and that both the hydrophilic and hydrophobic regions of SP-C are required for specific binding of a radiolabeled rough-type LPS. In addition, using LPS submitted to different chemical treatments as well as synthetic analogs of the lipid A moiety of LPS, we established that the terminal phosphate group at the reducing end of the lipid A disaccharide in alpha configuration is of crucial importance for recognition by SP-C. The N-linked fatty acyl chain on the reducing glucosamine of lipid A also takes part in the interaction. Dipalmitoyl phosphatidylcholine is not specifically required for the LPS-binding activity of SP-C, although a lipid environment significantly increases the binding. These results provide a basis for experiments on the role of SP-C in presentation of LPS to alveolar cells and for the design of drugs for the management of endotoxin-induced lung injury.

Background: In our phase 2b trials, patients (n=499) given 200 mg/d apabetalone (RVX-208) for 6 months were observed to have a 55% relative risk reduction of major adverse cardiovascular events (MACE) that was further reduced in diabetes mellitus (DM) patients. These findings underpin our interest

Stereolithography (SL) is a technique allowing additive manufacturing of complex ceramic parts by selective photopolymerization of a photocurable suspension containing photocurable monomer, photoinitiator, and a ceramic powder. The manufactured three-dimensional object is cleaned and converted into a dense ceramic part by thermal debinding of the polymer network and subsequent sintering. The debinding is the most critical and time-consuming step, and often the source of cracks. In this study, photocurable alumina suspensions have been developed, and the influence of resin composition on defect formation has been investigated. The suspensions were characterized in terms of rheology and curing behaviour, and cross-sections of sintered specimens manufactured by SL were evaluated by SEM. It was found that the addition of a non-reactive component to the photocurable resin reduced polymerization shrinkage and altered the thermal decomposition of the polymer matrix, which led to a reduction in both delamination and intra-laminar cracks. Using a non-reactive component that decomposed rather than evaporated led to less residual porosity.

In order to comprehensively evaluate the employee satisfaction of mine occupational health and safety management system, an analytic method based on fuzzy analytic hierarchy process and 2-tuple linguistic model was established. Based on the establishment of 5 first-grade indicators and 20 second-grade ones, method of improved AHP and the time-ordered Weighted Averaging Operator (T-OWA) model is constructed. The results demonstrate that the employee satisfaction of the mine occupational health and safety management system is of the ‘general’ rank. The method including the evaluation of employee satisfaction and the quantitative analysis of language evaluation information ensures the authenticity of the language evaluation information.

The ideal scaffold for engineering and regeneration of tissues would be a replica of the extracellular matrix (ECM), which is unique for each tissue type. The scaffold should mimic the mechanical properties of the targeted tissue and serve as matrix for adhesion, growth, migration, and differentiation of endogenous and/or implanted cells. Recent research has highlighted the potential of targeting also the environment of the intermediate states that are formed during tissue repair, since progenitor cells that contribute to tissue formation in a regenerative niche exist in an environment that is different from the final tissue (e.g., the fracture callus that is formed during osteogenesis is softer than mature bone tissue) (Polo-Corrales et al., 2014). In addition, the scaffold should not evoke inappropriate immune responses and should be degradable. To improve cell interactions, ECM-derived cell-binding peptide motifs have been extensively used (Sengupta and Heilshorn, 2010; Maia et al., 2013). For improving cell attachment to biomaterials, the RGD (Arg-Gly-Asp) peptide motif is commonly used. This peptide is found in fibronectin, vitronectin, bone sialoprotein (BSP), and collagen VI and is recognized by the αvβ3 integrin (Arnaout et al., 2005). The RGD motif exhibits its full binding activity to integrins only when its mobility is restricted in a loop conformation, which can be accomplished in vitro by the incorporation of RGD in a cyclic peptide structure (Kumagai et al., 1991; Mohri et al., 1991). In contrast, if the RGD motif is flexible and lacks a stable conformation, it has a much lower affinity to the αvβ3 integrin (Pfaff et al., 1994). RGD-based peptides have been covalently linked to homopolymers (Brandley and Schnaar, 1988; Kuo and Lauffenburger, 1993; Cook et al., 1997; Bolley et al., 2013), but also covalently incorporated in proteins produced in heterologous hosts, including spider silk-derived proteins (Bini et al., 2006; Wohlrab et al., 2012). Artificial spider silk made from recombinant proteins can form various two- and three-dimensional matrices that hold promise for culture of cells for tissue engineering (Bini et al., 2006; Wohlrab et al., 2012; Wu et al., 2014). These matrices are promising but to realize their full potential, they have to be assembled in a controlled and reproducible way. The recently determined physiological and molecular events that control spider silk formation (Andersson et al., 2014; Kronqvist et al., 2014) have made this realistic for the first time. Functionalization of the silk matrices with cell adhesion motifs via genetic engineering may be a great advantage of the material that likely allows incorporation of cues for adhesion of specific cells, but this has not been fully investigated. Bini et al. compared films made from a recombinantly produced segment derived from the repetitive part of major ampullate spidroin (MaSp) from Nephila clavipes with or without an RGD motif incorporated, and analyzed Ca2+ deposition as a measure of cell response and human mesenchymal stem (hMSC) growth (Bini et al., 2006). The authors found that the matrix containing RGD did not show enhanced function as regard cell outcomes and speculated that the lack of RGD effect may be caused by insufficient exposure on the films. Wohlrab et al. studied growth of the cell line BALB/3T3 derived from mouse fibroblasts on films made from a recombinant protein segment from MaSp2 from Araneus diadematus (Wohlrab et al., 2012). RGD was either genetically incorporated into the silk protein, or added by linking a cyclic RGD peptide to Cys residues incorporated into the MaSp-derived protein. In both cases, adhesion and proliferation was improved compared to the wild-type protein as well as to a variant in which genetically incorporated RGD was replaced with RGE, a control motif, which binds significantly weaker to integrins. Widhe et al. reported that genetic incorporation of RGD into artificial silk, based on the minispidroin 4RepCT derived from Euprosthenops australis MaSp1, improved adherence and growth of human primary fibroblasts compared to 4RepCT films. Incorporation of the control motif RGE was reported to result in decreased attachment and about 50% slower growth rate compared to the RGD-4RepCT (Widhe et al., 2013). However, growth curves for RGD- and RGE-modified matrices were not analyzed. Wu et al., in contrast, found that the RGD-4RepCT films did not improve attachment of human embryonic stem cells (hESC) compared to wild-type 4RepCT, while incorporation of RGD within the longer vitronectin-derived peptide motif PQVTRGDVFTM resulted in efficient hESC attachment and growth. The effect of the vitronectin-derived peptide motif required integrin binding to the RGD motif, as evidenced by a competition experiment (Wu et al., 2014). The differences between Wohlrab et al. and Widhe et al. on the one hand and Wu et al. on the other hand may depend on that hESC are demanding to culture in vitro, while cell lines and fibroblast are robust and will attach to and grow on a wide range of supports and matrices. To test this hypothesis, we performed the same experiments as in Widhe et al. but analyzed the growth curves for human primary fibroblasts on RGD- and RGE-containing films. Surprisingly, we found that human fibroblasts grow equally well on RGD- and RGE-functionalized 4RepCT films (Figure ​(Figure11). Figure 1 Cell growth on functionalized spider silk matrices. Growth curves for primary human fibroblasts grown on RGD-4RepCT, RGE-4RepCT, and 4RepCT films, respectively, as described in Widhe et al. (2013). Cell growth was monitored with Alamar Blue cell viability ... The different results as regard the functional importance of RGD incorporated into spider silk-derived matrices for cell culture described above suggest that care must be taken when evaluating different silk-derived biomaterials. The cells used for culture must certainly be chosen with respect to intended eventual applications of the material, but the robustness of the cells, in particular their sensitivity to growth conditions, must also be considered. Cell types that are more insensitive to culture conditions, like immortalized cell lines or fibroblasts, may be unsuitable for critical testing of novel biomaterials. It is also important to compare matrices that are functionalized with motifs with presumed biological effects, like RGD, with negative controls, as indirect effects of incorporating novel peptide segments, e.g., mediated by altered general properties of the biomaterial, cannot be excluded.

The amyloid-β hypothesis of Alzheimer's Disease (AD) focuses on accumulation of amyloid-β peptide (Aβ) as the main culprit for the myriad physiological changes seen during development and progression of AD including desynchronization of neuronal action potentials, consequent development of aberrant brain rhythms relevant for cognition, and final emergence of cognitive deficits.The aim of this study was to elucidate the cellular and synaptic mechanisms underlying the Aβ-induced degradation of gamma oscillations in AD, to identify aggregation state(s) of Aβ that mediate the peptides neurotoxicity, and to test ways to prevent the neurotoxic Aβ effect.We show that Aβ1-42in physiological concentrations acutely degrades mouse hippocampal gamma oscillations in a concentration- and time-dependent manner. The underlying cause is an Aβ-induced desynchronization of action potential generation in pyramidal cells and a shift of the excitatory/inhibitory equilibrium in the hippocampal network. Using purified preparations containing different aggregation states of Aβ, as well as a designed ligand and a BRICHOS chaperone domain, we provide evidence that the severity of Aβ neurotoxicity increases with increasing concentration of fibrillar over monomeric Aβ forms, and that Aβ-induced degradation of gamma oscillations and excitatory/inhibitory equilibrium is prevented by compounds that interfere with Aβ aggregation.Our study provides correlative evidence for a link between Aβ-induced effects on synaptic currents and AD-relevant neuronal network oscillations, identifies the responsible aggregation state of Aβ and proofs that strategies preventing peptide aggregation are able to prevent the deleterious action of Aβ on the excitatory/inhibitory equilibrium and on the gamma rhythm.