Enzyme-induced Formation of ß-Lactoglobulin Fibrils by AspN Endoproteinase

This paper describes a low temperature, enzymatic route to induce fibrillar structures in a protein solution. The route comprises two steps. First, ß-lactoglobulin was hydrolyzed into peptides at pH 8 and 37°C with the enzyme AspN endoproteinase, which resulted in the formation of random aggregates. After hydrolysis, the pH was lowered to 2. As a result, long fibrillar aggregates were formed which was observed using transmission electron microscopy and Thioflavin T fluorescence measurements

Local corticosteroid injection versus Cyriax-type physiotherapy for tennis elbow

We performed a prospective, randomised trial on 106 patients to compare the effects of local corticosteroid injections with physiotherapy as advocated by Cyriax in the treatment of tennis elbow. The main outcome measures were the severity of pain, pain provoked by resisted dorsiflexion of the wrist, and patient satisfaction. At six weeks 22 of 53 patients in the injection group were free from pain compared with only three in the physiotherapy group. In the corticosteroid-treated group 26 patients had no pain on resisted dorsiflexion of the wrist compared with only three in the physiotherapy group. Thirty-five patients who had injections and 14 who had physiotherapy were satisfied with the outcome of treatment at six weeks. At the final assessment there were 18 excellent and 18 good results in the corticosteroid group and one excellent and 12 good results in the physiotherapy group. There was a significant increase in grip strength in both groups but those with injections had a significantly better result. After one year there were no significant differences between the two groups. Half of the patients, however, had received only the initial treatment, 20% had had combined therapy and 30% had had surgery. We conclude that at six weeks, treatment with corticosteroid injections was more effective than Cyriax physiotherapy and we recommend it because of its rapid action, reduction of pain and absence of side-effects

A prospective methicillin resistant staphylococcus aureus typing system for infection control : design and effectiveness

The uptake of Gadomer-17, as probed by fast dynamic T(1) measurements, was used to assess the vascular permeability surface-area product per leakage volume of tissue (k(Tofts)) of human glioma xenografts implanted in mice. With this approach we could discriminate between two types of glioma xenograft lines with a known difference in the perfused vascular architecture and degree of hypoxia. The T(1) data were analyzed according to the Tofts-Kermode compartment model. The fast-growing E102 tumor demonstrated a homogeneous distribution of the vascular permeability surface area across the tumor (mean k(Tofts) value = 0.18 +/- 0.05 min(-1)). The slowly growing E106 tumor showed a more heterogeneous pattern. Three perfused tumor areas with differences in vascular permeability surface area could be distinguished: a well-perfused periphery with high k(Tofts) values (0.24 +/- 0.04 min(-1)), perfused capillaries inside the tumor with low k(Tofts) values (0.108 +/- 0.026 min(-1)), and perfused capillaries adjacent to necrotic regions with high k(Tofts) values (0.29 +/- 0.10 min(-1)). On a different series of tumors, the hypoxic fractions were measured, and these were significantly higher in E106 tumors (0.14 +/- 0.05) compared to tumors of the E102 line (0.03 +/- 0.02)

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE-/- mice

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes. Methods ApoE−/− mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells. Results Surgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged. Conclusions Major orthopedic surgery in ApoE−/− mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated. © 2016 Elsevier Ireland Lt

Hypofractionated radiotherapy combined with targeted therapy or immunotherapy: Dutch survey on current practice, knowledge and challenges

Introduction: With the introduction of tyrosine kinase inhibitors and systemic antibodies, including immune checkpoint inhibitors, the survival of advanced-stage cancer patients has improved for many tumor types. These patients are increasingly referred for radiotherapy, but it is unclear whether radiotherapy combined with these drugs is safe. No international guidelines exist on whether or how to combine these drugs with radiotherapy. Therefore, we investigated the current clinical practice in the Netherlands regarding hypofractionated radiotherapy in patients using targeted drugs and immunotherapy.Materials and methods: We sent a survey to all 21 Dutch radiotherapy institutes. Dedicated radiation oncologists, medical oncologists and pulmonologists were asked to fill out the survey. The questions explored their familiarity with the combination of targeted drugs and immunotherapy with radiotherapy, the encountered clinical difficulties and factors influencing treatment decisions.Results: The survey was filled out by 54 respondents from 19 different institutes. The median annual number of patients per radiation oncologist referred for radiotherapy when using targeted drugs or immunotherapy was 10 and 15, respectively. Despite this high number, only 11% of the radiation oncologists stated that they had sufficient information (resources) for adequate treatment decision making. Among all physicians, 44% stated that there was insufficient knowledge within their institute regarding this topic. Only 17% stated that there was a multidisciplinary protocol available. The application of radiotherapy treatment adaptations (technique, dose, fractionation, field size) varied widely. Generally, there seemed to be no consensus regarding the expected toxicity of combined drug-radiotherapy treatments and the expected risk of tumor flare upon temporary drug discontinuation.Conclusion: There is no consensus amongst involved medical specialties on expected toxicity. Consequently, it is necessary to perform clinical studies examining the safety of combined drug-radiotherapy treatments, to add radiotherapy to phase I-III clinical trials for new drugs and to incorporate outcomes into multidisciplinary, evidence-based guidelines.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

How Universal Is the General Factor of Personality?

In various personality models, such as the Big Five, a consistent higher order general factor of personality (GFP) can be identified. One view in the literature is that the GFP reflects general social effectiveness. Most GFP studies, however, have been conducted in Western, educated, industrialized, and rich democracies (WEIRD). Therefore, to address the question of the universality of the GFP, we test whether the GFP can also be identified in a preliterate indigenous sample of Tsimane by using self-reports, spouse reports, and interviewer ratings. In the Tsimane, a viable GFP could be identified and the intercorrelations between personality traits were significantly stronger than in samples from industrial countries. The GFP correlated with the ratings of social engagement. In addition, self and spouse ratings of the GFP overlapped. Overall, the findings are in line with the notion that the GFP is a human universal and a substantive personality factor reflecting social effectiveness

Uniform hopping approach to the FM Kondo Model at finite temperature

We study the ferromagnetic Kondo model with classical corespins via unbiased Monte-Carlo simulations and derive a simplified model for the treatment of the corespins at any temperature. Our simplified model captures the main aspects of the Kondo model and can easily be evaluated both numerically and analytically. It provides a better qualitative understanding of the physical features of the Kondo model and rationalizes the Monte-Carlo results, including the spectral density A_k(omega) of a 1D chain with nearest neighbor Coulomb repulsion. By calculating the specific heat and the susceptibility of systems up to size 16^3, we determine the Curie temperature of the 3D one-orbital double-exchange model, which agrees with experimental values.Comment: 11 pages, 9 figures, RevTex4, additional references cite