Topography-Mediated Fibroblast Cell Migration Is Influenced by Direction, Wavelength, and Amplitude

Biophysical stimuli including topography play a crucial role in the regulation of cell morphology, adhesion, migration, and cytoskeleton organization and have been known to be important in biomaterials design for tissue engineering. However, little is known about the individual effects of topographic direction, structure repetition, and feature size of the substrate on which wound healing occurs. We report on the design of a topographical gradient with wavelike features that gradually change in wavelength and amplitude, which provides an efficient platform for an in vitro wound healing assay to investigate fibroblast migration. The wound coverage rate was measured on selected areas with wavelength sizes of 2, 5, and 8 mu m in perpendicular and parallel orientations. Furthermore, a method was developed to produce independently controlled wavelength and amplitude and study which parameter has greater influence. Cell movement was guided by topographical properties, with a lower wrinkle wavelength (2 mu m) eliciting the fastest migration speed, and the migration speed increased with decreasing amplitude. However, when the amplitudes were matched, cells migrated faster on a larger wavelength. This study also highlights the sensitivity of fibroblasts to the topographic orientation, with cells moving faster in the parallel direction of the topography. The overall behavior indicated that the wavelength and amplitude both play an important role in directing cell migration. The collective cell migration was found not to be influenced by altered cell proliferation. These findings provide key insights into topography-triggered cell migration and indicate the necessity for better understanding of material-directed wound healing for designing bio-inductive biomaterials

Simultaneous flow cytometric detection of antibodies against platelets, granulocytes and lymphocytes

We present a time-saving and objective flow cytometric immunofluorescence assay for the simultaneous detection of antibodies against platelets, granulocytes or lymphocytes using a reconstituted mixture of these cell populations. Platelets, granulocytes and lymphocytes could be distinguished on the basis of their forward (FSC) and sideways (SSC) light scattering properties plotted on scales of 4 log orders. After setting FSC/SSC gates around the platelets, granulocytes and lymphocytes, the reactivity of the sera with the cell populations was determined by histogram analyses of immunofluorescence for each gate. The flow cytometric assay of reconstituted cell mixtures showed a strong, positive correlation with a reference microscopic immunofluorescence assay of separate cell suspensions. The reproducible procedures for the isolation and staining of the cells and the electronic stability of the flow cytometer permitted the use of the same gate and marker settings throughout the experiments. Consequently, the entire analysis of data stored in list mode could be performed using a keystroke, so that time consuming and subjective manual analyses were avoided

Non-small-bowel abnormalities identified during small bowel capsule endoscopy

AIM: To investigate the incidence of non-small-bowel abnormalities in patients referred for small bowel capsule endoscopy, this single center study was performed. METHODS: Small bowel capsule endoscopy is an accepted technique to investigate obscure gastrointestinal bleeding. This is defined as bleeding from the digestive tract that persists or recurs without an obvious etiology after a normal gastroduodenoscopy and colonoscopy. Nevertheless, capsule endoscopy sometimes reveals findings outside the small bowel, i. e., within reach of conventional endoscopes. In this retrospective single center study, 595 patients undergoing capsule endoscopy between 2003 and 2009 were studied. The incidence of non-small bowel abnormalities was defined as visible abnormalities detected by capsule endoscopy that are located within reach of conventional endoscopes. RESULTS: In 595 patients, referred for obscure gas-trointestinal bleeding or for suspected Crohn's disease, abnormalities were found in 306 (51.4%). Of these 306 patients, 85 (27.7%) had abnormalities within reach of conventional endoscopes; 63 had abnormalities apparently overlooked at previous conventional endoscopies, 10 patients had not undergone upper and lower endoscopy prior to capsule endoscopy and 12 had abnormalities that were already known prior to capsule endoscopy. The most common type of missed lesions were vascular lesions (n = 47). Non-small-bowel abnormalities were located in the stomach (n = 15), proximal small bowel (n = 22), terminal ileum (n = 21), colon (n = 19) or at other or multiple locations (n = 8). Ten patients with abnormal findings in the terminal ileum had not undergone examination of the ileum during colonoscopy. CONCLUSION: A significant proportion of patients undergoing small bowel capsule endoscopy had lesions within reach of conventional endoscopes, indicating that capsule endoscopy was unnecessarily performed. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved

Toezicht door private partijen: panacee voor alle kwalen?

Naast het traditionele verticale toezicht van de overheid op het bedrijfsleven hebben zich de afgelopen jaren steeds meer vormen van horizontaal toezicht ontwikkeld. Deze kenmerken zich door onderlinge samenwerking en vertrouwen tussen publieke en private partijen. Voorbeelden hiervan zijn onder meer compliance assistance, certificering en systeemtoezicht. De overheid (publieke toezichthouder) treedt in al die varianten terug en maakt plaats voor private toezichthouders die namens producenten, consumenten of andere belangengroepen optreden. Deze ontwikkelingen vormden de aanleiding voor het organiseren van een symposium over toezicht door private partijen op 26 maart 2009. Wetenschappers en practitioners stonden stil bij een tweetal vragen. In de eerste plaats de vraag op welke wijze deze nieuwe vormen van toezicht in de praktijk worden uitgeoefend en, ten tweede, in hoeverre kan het toezicht aan private partijen worden toevertrouwd? Zeker nu het maatschappelijk vertrouwen in het zelfregulerend vermogen van ondernemingen door de kredietcrisis ernstig is geschaad. Deze bundel bevat het verslag van het symposium in de vorm van de bijdragen van de sprekers en een algemene inleiding. Het toezicht in twee sectoren is onder de loep genomen: toezicht op financiële markten en op de naleving van milieuvoorschriften

On the potential for discontinuing atovaquone-proguanil (AP) ad-hoc post-exposure and other abbreviated AP-regimens: Pharmacology, pharmacokinetics and perspectives

According to current guidelines, atovaquone-proguanil (AP) malaria chemoprophylaxis should be taken once daily starting one day before travel and continued for seven days post-exposure. However, drug-sparing regimens, including discontinuing AP after leaving malaria-endemic areas are cost-saving and probably more attractive to travelers, and may thus enhance adherence. AP has causal prophylactic effects, killing malaria parasites during the hepatic stage. If early hepatic stages were already targeted by AP, AP could possibly be discontinued upon return. Pharmacokinetic data and studies on drug-sparing AP regimens suggest this to be the case. Nevertheless, the evidence is weak and considered insufficient to modify current recommendations. Field trials require large numbers of travelers and inherently suffer from the lack of a control group. Safely-designed controlled human malaria infection trials could significantly reduce study participant numbers and safely establish an effective AP abbreviated regimen which we propose as the optimal trial design to test this concept

Market Efficiency after the Financial Crisis: It's Still a Matter of Information Costs

Compared to the worldwide financial carnage that followed the Subprime Crisis of 2007-2008, it may seem of small consequence that it is also said to have demonstrated the bankruptcy of an academic financial institution: the Efficient Capital Market Hypothesis (“ECMH”). Two things make this encounter between theory and seemingly inconvenient facts of consequence. First, the ECMH had moved beyond academia, fueling decades of a deregulatory agenda. Second, when economic theory moves from academics to policy, it also enters the realm of politics, and is inevitably refashioned to serve the goals of political argument. This happened starkly with the ECMH. It was subject to its own bubble – as a result of politics, it expanded from a narrow but important academic theory about the informational underpinnings of market prices to a broad ideological preference for market outcomes over even measured regulation. In this Article we examine the Subprime Crisis as a vehicle to return the ECMH to its information cost roots that support a more modest but sensible regulatory policy. In particular, we argue that the ECMH addresses informational efficiency, which is a relative, not an absolute measure. This focus on informational efficiency leads to a more focused understanding of what went wrong in 2007-2008. Yet informational efficiency is related to fundamental efficiency – if all information relevant to determining a security’s fundamental value is publicly available and the mechanisms by which that information comes to be reflected in the securities market price operate without friction, fundamental and informational efficiency coincide. But where all value relevant information is not publicly available and/or the mechanisms of market efficiency operate with frictions, the coincidence is an empirical question both as to the information efficiency of prices and their relation to fundamental value. Properly framing market efficiency focuses our attention on the frictions that drive a wedge between relative efficiency and efficiency under perfect market conditions. So framed, relative efficiency is a diagnostic tool that identifies the information costs and structural barriers that reduce price efficiency which, in turn, provides part of a realistic regulatory strategy. While it will not prevent future crises, improving the mechanisms of market efficiency will make prices more efficient, frictions more transparent, and the influence of politics on public agencies more observable, which may allow us to catch the next problem earlier. Recall that on September 8, 2008, the Congressional Budget Office publicly stated its uncertainty about whether there would be a recession and predicted 1.5 percent growth in 2009. Eight days later, Lehman Brothers had failed, and AIG was being nationalized

Validity of the self-administered comorbidity questionnaire in patients with inflammatory bowel disease

Background: The International Consortium for Health Outcomes Measurement has selected the self-administered comorbidity questionnaire (SCQ) to adjust case-mix when comparing outcomes of inflammatory bowel disease (IBD) treatment between healthcare providers. However, the SCQ has not been validated for use in IBD patients. Objectives: We assessed the validity of the SCQ for measuring comorbidities in IBD patients. Design: Cohort study. Methods: We assessed the criterion validity of the SCQ for IBD patients by comparing patient-reported and clinician-reported comorbidities (as noted in the electronic health record) of the 13 diseases of the SCQ using Cohen’s kappa. Construct validity was assessed using the Spearman correlation coefficient between the SCQ and the Charlson Comorbidity Index (CCI), clinician-reported SCQ, quality of life, IBD-related healthcare and productivity costs, prevalence of disability, and IBD disease activity. We assessed responsiveness by correlating changes in the SCQ with changes in healthcare costs, productivity costs, quality of life, and disease activity after 15 months. Results: We included 613 patients. At least fair agreement (κ &gt; 0.20) was found for most comorbidities, but the agreement was slight (κ &lt; 0.20) for stomach disease [κ = 0.19, 95% CI (−0.03; 0.41)], blood disease [κ = 0.02, 95% CI (−0.06; 0.11)], and back pain [κ = 0.18, 95% CI (0.11; 0.25)]. Correlations were found between the SCQ and the clinician-reported SCQ [ρ = 0.60, 95% CI (0.55; 0.66)], CCI [ρ = 0.39, 95% CI (0.31; 0.45)], the prevalence of disability [ρ = 0.23, 95% CI (0.15; 0.32)], and quality of life [ρ = −0.30, 95% CI (−0.37; −0.22)], but not between the SCQ and healthcare or productivity costs or disease activity (|ρ| ⩽ 0.2). A change in the SCQ after 15 months was not correlated with a change in any of the outcomes.Conclusion: The SCQ is a valid tool for measuring comorbidity in IBD patients, but face and content validity should be improved before being used to correct case-mix differences.</p

Parental social contact in the work place and the risk of childhood acute lymphoblastic leukaemia

To study the possible relation between parental social contact through occupation, a marker for a child's risk of infection, and childhood acute lymphoblastic leukaemia (ALL), the parents of 294 children with ALL aged 0–14.9 years and 376 matched controls were interviewed about their jobs after their child's birth up to the age of 3 years. Job titles were assigned to a level of social contact, and an index of occupational social contact months was created using the level and the job duration. Positive interactions between this index and rural residence associated with an increased risk of childhood ALL and common ALL (c-ALL) were observed (interaction P-value=0.02 for both, using tertiles of contact months; interaction P-value=0.05 and 0.02 for ALL and c-ALL, respectively, using continuous contact months); such findings were not observed when job durations were ignored. Our data suggest that duration of parental occupation may be important when examining the association between parental social contact in the workplace and childhood leukaemia