Application of fluorescence techniques to the study of protein adsorption and packing on biomaterial surfaces

[Excerpt] The ways proteins compete for the surface of biomaterials and change conformation are believed to be important for the host response to implants. It is possible to elucidate information on packing and any induced conformational change by making use of different fluorescence techniques on fluorescently labelled proteins. Employing probe-probe resonance energy transfer (RET) allows inter and intra protein interactions to be distinguished. Homo resonance energy transfer (hRET) avoids many problems with having two different probes and means that labelling and subsequent purification can be done in one step. [...]Portuguese Foundation for Science and Technology, project PROTEOLIGHT (PTDC/FIS/68517/2006) and J.B. grant SFRH/BPD/17584/2004. European Union NoE EXPERTISSUES (NMP3-CT-2004-500283) and European Union FP6 STREP project HIPPOCRATES (NMP3-CT-2003-505758).info:eu-repo/semantics/publishedVersio

Fermiology via the electron momentum distribution

Investigations of the Fermi surface via the electron momentum distribution reconstructed from either angular correlation of annihilation radiation (or Compton scattering) experimental spectra are presented. The basis of these experiments and mathematical methods applied in reconstructing three-dimensional densities from line (or plane) projections measured in these experiments are described. The review of papers where such techniques have been applied to study the Fermi surface of metallic materials with showing their main results is also done.Comment: 22 pages, 9 Figures, 4 Table

Narrowband ultraviolet B response in cutaneous T-cell lymphoma is characterized by increased bacterial diversity and reduced Staphylococcus aureus and Staphylococcus lugdunensis

Skin microbiota have been linked to disease activity in cutaneous T-cell lymphoma (CTCL). As the skin microbiome has been shown to change after exposure to narrowband ultraviolet B (nbUVB) phototherapy, a common treatment modality used for CTCL, we performed a longitudinal analysis of the skin microbiome in CTCL patients treated with nbUVB. 16S V4 rRNA gene amplicon sequencing for genus-level taxonomic resolution, tuf2 amplicon next generation sequencing for staphylococcal speciation, and bioinformatics were performed on DNA extracted from skin swabs taken from lesional and non-lesional skin of 25 CTCL patients receiving nbUVB and 15 CTCL patients not receiving nbUVB from the same geographical region. Disease responsiveness to nbUVB was determined using the modified Severity Weighted Assessment Tool: 14 (56%) patients responded to nbUVB while 11 (44%) patients had progressive disease. Microbial α-diversity increased in nbUVB-responders after phototherapy. The relative abundance of Staphylococcus, Corynebacterium, Acinetobacter, Streptococcus, and Anaerococcus differentiated nbUVB responders and non-responders after treatment (q\u3c0.05). Microbial signatures of nbUVB-treated patients demonstrated significant post-exposure depletion of S. aureus (q=0.024) and S. lugdunensis (q=0.004) relative abundances. Before nbUVB, responder lesional skin harboured higher levels of S. capitis (q=0.028) and S. warneri (q=0.026) than non-responder lesional skin. S. capitis relative abundance increased in the lesional skin of responders (q=0.05) after phototherapy; a similar upward trend was observed in non-responders (q=0.09). Post-treatment skin of responders exhibited significantly reduced S. aureus (q=0.008) and significantly increased S. hominis (q=0.006), S. pettenkoferi (q=0.021), and S. warneri (q=0.029) relative abundances compared to that of no-nbUVB patients. Staphylococcus species abundance was more similar between non-responders and no-nbUVB patients than between responders and no-nbUVB patients. In sum, the skin microbiome of CTCL patients who respond to nbUVB is different from that of non-responders and untreated patients, and is characterized by shifts in S. aureus and S. lugdunensis. Non-responsiveness to phototherapy may reflect more aggressive disease at baseline

A comparison of rotation- and blob-based system models for 3D SPECT with depth-dependent detector response

We compare two different implementations of a 3D SPECT system model for iterative reconstruction, both of which compensate for non-uniform photon attenuation and depth-dependent system response. One implementation performs fast rotation of images represented using a basis of rectangular voxels, whereas the other represents images using a basis of rotationally symmetric volume elements. In our simulations the blob-based approach was found to slightly outperform the rotation-based one in terms of the bias-variance trade-off in the reconstructed images. Their difference can be significant, however, in terms of computational load. The rotation-based method is faster for many typical SPECT reconstruction problems, but the blob-based one can be better-suited to cases where the reconstruction algorithm needs to process one volume element at a time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48977/2/pmb4_11_003.pd

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of \u27severe\u27 or \u27moderate\u27 patients improving to \u27mild\u27 or \u27slight\u27. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients

Are female students in general and nursing students more ready for teamwork and interprofessional collaboration in healthcare?

<p>Abstract</p> <p>Background</p> <p>Interprofessional Education (IPE) is now spreading worldwide and many universities are now including IPE in their curricula. The aim of this study was to investigate whether or not such student characteristics as gender, previous working experience in healthcare, educational progress and features of the learning environment, such as educational programmes and curriculum design, have an impact on their open-mindedness about co-operation with other professions.</p> <p>Methods</p> <p>Medical and nursing students at two Swedish universities were invited to fill in the Readiness for Interprofessional Learning Scale (RIPLS). Totally, 955 students were invited and 70.2% (n = 670) participated in the study. A factor analysis of the RIPLS revealed four item groupings (factors) for our empirical data, but only one had sufficient internal consistency. This factor was labelled "Team Player".</p> <p>Results</p> <p>Regardless of the educational programme, female students were more positive to teamwork than male students. Nursing students in general displayed more positive beliefs about teamwork and collaboration than medical students. Exposure to different interprofessional curricula and previous exposure to interprofessional education were only to a minor extent associated with a positive attitude towards teamwork. Educational progress did not seem to influence these beliefs.</p> <p>Conclusions</p> <p>The establishment of interprofessional teamwork is a major challenge for modern healthcare. This study indicates some directions for more successful interprofessional education. Efforts should be directed at informing particularly male medical students about the need for teamwork in modern healthcare systems. The results also imply that study of other factors, such as the student's personality, is needed for fully understanding readiness for teamwork and interprofessional collaboration in healthcare. We also believe that the RIPL Scale still can be further adjusted.</p

The placebo effect and its determinants in fibromyalgia: meta-analysis of randomized controlled trials

The aims of this study were to determine whether placebo treatment in randomised controlled trials (RCTs) is effective for fibromyalgia and to identify possible determinants of the magnitude of any such placebo effect. A systematic literature search was undertaken for RCTs in people with fibromyalgia that included a placebo and/or a no-treatment (observation only or waiting list) control group. Placebo effect size (ES) for pain and other outcomes was measured as the improvement of each outcome from baseline divided by the standard deviation of the change from baseline. This effect was compared with changes in the no-treatment control groups. Meta-analysis was undertaken to combine data from different studies. Subgroup analysis was conducted to identify possible determinants of the placebo ES. A total of 3912 studies were identified from the literature search. After scrutiny, 229 trials met the inclusion criteria. Participants who received placebo in the RCTs experienced significantly better improvements in pain, fatigue, sleep quality, physical function, and other main outcomes than those receiving no treatment. The ES of placebo for pain relief was clinically moderate (0.53, 95%CI 0.48 to 0.57). The ES increased with increasing strength of the active treatment, increasing participant age and higher baseline pain severity, but decreased in RCTS with more women and with longer duration of fibromyalgia. In addition, placebo treatment in RCTs is effective in fibromyalgia. A number of factors (expected strength of treatment, age, gender, disease duration) appear to influence the magnitude of the placebo effect in this condition

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130±27.6% (P<0.05) similar to that induced by VEGF and with which it is additive (281±13%) (P<0.05). Moreover, specific blockade of the receptor (either by α IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours