Interventions for preventing oral mucositis for patients with cancer receiving treatment

Interventions for preventing oral mucositis for patients with cancer receiving treatmentTreatment for cancer (including bone marrow transplant) can cause oral mucositis (severe ulcers in the mouth). This painful condition can cause difficulties in eating, drinking and swallowing, and may also be associated with infections which may require the patient to stay longer in hospital. Different strategies are used to try and prevent this condition, and the review of trials found that some of these are effective. Two interventions, cryotherapy (ice chips) and keratinocyte growth factor (palifermin®) showed some benefit in preventing mucositis. Sucralfate is effective in reducing the severity of mucositis, and a further seven interventions, aloe vera, amifostine, intravenous glutamine, granulocyte‐colony stimulating factor (G‐CSF), honey, laser and antibiotic lozenges containing polymixin/tobramycin/amphotericin (PTA) showed weaker evidence of benefit. These were evaluated in patients with different types of cancer, undergoing different types of cancer treatment. Benefits may be restricted to the disease and treatment combinations evaluated

Influence of type of contraction upon tendinous tissue during training: animal model

peer reviewedIntroduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Materiel and methods: This study compared the effects of two methods of training (eccentric (E) training and concentric (C) training) with untrained (U) rats. The animals underwent training over a period of five weeks. The tricipital, patellar and Achilles tendons were subsequently removed to perform a traction test to the point of tendon rupture, and a histological analysis was performed. Results: There was a significant improvement in the rupture force of the patellar and tricipital tendons between the U and E groups. The tricipital tendons in the control group presented a significantly smaller cross-section than the E- and C-trained groups. No significant difference was observed for the constraints between the three groups for all three tendons. However, a tendency towards improvement was observed between the trained and the U groups for the patellar tendon. Histological studies demonstrated the development of a greater number of blood vessels and a larger quantity of collagen in the eccentric group. Discussion and conclusion: The mechanical properties of tendons in rats improve after specific training, especially following eccentric training

Influence du mode de contraction sur le tendon : modèle animal

peer reviewedIntroduction : Les tendinopathies sont fréquentes et touchent aussi bien les membres supérieurs que les membres inférieurs. La rééducation excentrique constitue une thérapeutique de choix dans le traitement des tendinopathies. Malgré les résultats favorables en clinique, les effets morphologiques et biochimiques n’ont pas encore été élucidés. Matériel et méthodes : Dix-huit rats de souche Sprague-Dawley adultes ont été répartis en trois groupes : 6 témoins (groupe T) qui ne sont soumis à aucune contrainte physique ; 6 soumis à un effort concentrique (groupe C), course en montée ; 6 soumis à un effort excentrique (groupe E), course en descente. Les 12 rats des groupes C et E ont dû courir sur un tapis roulant incliné à +15° (groupe C) ou -15° (groupe E) à une vitesse de 17m/min (1km/h) pendant une heure à raison de trois séances par semaine pendant 5 semaines. Au terme de l’entraînement, les tendons achilléens, rotuliens et tricipitaux ont été prélevés bilatéralement. Les tendons de cinq rats de chaque groupe ont bénéficié d’une évaluation biomécanique (test de traction à l’aide de mors type « cryo-jaws »). Les tendons du sixième rat de chaque groupe ont permis l’étude histologique (coloration à l’hématoxyline-éosine et trichrome de Masson). Résultats : Le groupe E présente une augmentation de la tension de rupture des tendons rotuliens (29 ,5% ; p=0,047) et tricipitaux (72% ; p=0,018), une amélioration du rapport Force/Masse pour le tendon tricipital (54% ; p=0,043) ainsi qu’une augmentation de la section tendineuse tricipitale (74% ; p=0,008). Aucune variation pour aucun des tendons entre les groupes n’est relevée pour le paramètre contrainte (=Force/Section). Histologiquement, les tendons du groupe E se caractérisent par une plus grande quantité de vaisseaux sanguins périphériques ainsi qu’une plus grande proportion de collagène. Conclusion : Cette étude démontre que les propriétés mécaniques du tendon sont améliorées après un entraînement excentrique. Le tendon plus résistant augmente sa quantité de collagène et probablement les interactions entre les fibres de collagène

Planck Intermediate Results II: Comparison of Sunyaev-Zeldovich measurements from Planck and from the Arcminute Microkelvin Imager for 11 galaxy clusters

A comparison is presented of Sunyaev-Zeldovich measurements for 11 galaxy clusters as obtained by Planck and by the ground-based interferometer, the Arcminute Microkelvin Imager. Assuming a universal spherically-symmetric Generalised Navarro, Frenk & White (GNFW) model for the cluster gas pressure profile, we jointly constrain the integrated Compton-Y parameter (Y_500) and the scale radius (theta_500) of each cluster. Our resulting constraints in the Y_500-theta_500 2D parameter space derived from the two instruments overlap significantly for eight of the clusters, although, overall, there is a tendency for AMI to find the Sunyaev-Zeldovich signal to be smaller in angular size and fainter than Planck. Significant discrepancies exist for the three remaining clusters in the sample, namely A1413, A1914, and the newly-discovered Planck cluster PLCKESZ G139.59+24.18. The robustness of the analysis of both the Planck and AMI data is demonstrated through the use of detailed simulations, which also discount confusion from residual point (radio) sources and from diffuse astrophysical foregrounds as possible explanations for the discrepancies found. For a subset of our cluster sample, we have investigated the dependence of our results on the assumed pressure profile by repeating the analysis adopting the best-fitting GNFW profile shape which best matches X-ray observations. Adopting the best-fitting profile shape from the X-ray data does not, in general, resolve the discrepancies found in this subset of five clusters. Though based on a small sample, our results suggest that the adopted GNFW model may not be sufficiently flexible to describe clusters universally.Comment: update to metadata author list onl

No jacket required – new fungal lineage defies dress code

Analyses of environmental DNAs have provided tantalizing evidence for “rozellida” or “cryptomycota”, a clade of mostly undescribed and deeply diverging aquatic fungi. Here, we put cryptomycota into perspective through consideration of Rozella , the only clade member growing in culture. This is timely on account of the publication in Nature of the first images of uncultured cryptomycota from environmental filtrates, where molecular probes revealed non‐motile cyst‐like structures and motile spores, all lacking typical fungal chitinous cell walls. Current studies of Rozella can complement these fragmentary observations from environmental samples. Rozella has a fungal‐specific chitin synthase and its resting sporangia have walls that appear to contain chitin. Cryptomycota, including Rozella , lack a cell wall when absorbing food but like some other fungi, they may have lost their “dinner jacket” through convergence. Rather than evolutionary intermediates, the cryptomycota may be strange, divergent fungi that evolved from an ancestor with a nearly complete suite of classical fungal‐specific characters.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90101/1/94_ftp.pd

In Silico Ascription of Gene Expression Differences to Tumor and Stromal Cells in a Model to Study Impact on Breast Cancer Outcome

Breast tumors consist of several different tissue components. Despite the heterogeneity, most gene expression analyses have traditionally been performed without prior microdissection of the tissue sample. Thus, the gene expression profiles obtained reflect the mRNA contribution from the various tissue components. We utilized histopathological estimations of area fractions of tumor and stromal tissue components in 198 fresh-frozen breast tumor tissue samples for a cell type-associated gene expression analysis associated with distant metastasis. Sets of differentially expressed gene-probes were identified in tumors from patients who developed distant metastasis compared with those who did not, by weighing the contribution from each tumor with the relative content of stromal and tumor epithelial cells in their individual tumor specimen. The analyses were performed under various assumptions of mRNA transcription level from tumor epithelial cells compared with stromal cells. A set of 30 differentially expressed gene-probes was ascribed solely to carcinoma cells. Furthermore, two sets of 38 and five differentially expressed gene-probes were mostly associated to tumor epithelial and stromal cells, respectively. Finally, a set of 26 differentially expressed gene-probes was identified independently of cell type focus. The differentially expressed genes were validated in independent gene expression data from a set of laser capture microdissected invasive ductal carcinomas. We present a method for identifying and ascribing differentially expressed genes to tumor epithelial and/or stromal cells, by utilizing pathologic information and weighted t-statistics. Although a transcriptional contribution from the stromal cell fraction is detectable in microarray experiments performed on bulk tumor, the gene expression differences between the distant metastasis and no distant metastasis group were mostly ascribed to the tumor epithelial cells of the primary breast tumors. However, the gene PIP5K2A was found significantly elevated in stroma cells in distant metastasis group, compared to stroma in no distant metastasis group. These findings were confirmed in gene expression data from the representative compartments from microdissected breast tissue. The method described was also found to be robust to different histopathological procedures

Mitoxantrone Induces Natural Killer Cell Maturation in Patients with Secondary Progressive Multiple Sclerosis

Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone on the immune system is poorly understood. Thus, to develop safe therapeutic approaches for patients with progressive MS, it is essential to elucidate how mitoxantrone exerts it benefits. Accordingly, we initiated a prospective single-arm open-label study with 19 secondary progressive MS patients. We investigated long-term effects of mitoxantrone on patient peripheral immune subsets using flow cytometry. While we corroborate that mitoxantrone persistently suppresses B cells in vivo, we show for the first time that treatment led to an enrichment of neutrophils and immunomodulatory CD8low T cells. Moreover, sustained mitoxantrone applications promoted not only persistent NK cell enrichment but also NK cell maturation. Importantly, this mitoxantrone-induced NK cell maturation was seen only in patients that showed a clinical response to treatment. Our data emphasize the complex immunomodulatory role of mitoxantrone, which may account for its benefit in MS. In particular, these results highlight the contribution of NK cells to mitoxantrone efficacy in progressive MS

Time-resolved single-crystal X-ray crystallography

In this chapter the development of time-resolved crystallography is traced from its beginnings more than 30 years ago. The importance of being able to “watch” chemical processes as they occur rather than just being limited to three-dimensional pictures of the reactant and final product is emphasised, and time-resolved crystallography provides the opportunity to bring the dimension of time into the crystallographic experiment. The technique has evolved in time with developments in technology: synchrotron radiation, cryoscopic techniques, tuneable lasers, increased computing power and vastly improved X-ray detectors. The shorter the lifetime of the species being studied, the more complex is the experiment. The chapter focusses on the results of solid-state reactions that are activated by light, since this process does not require the addition of a reagent to the crystalline material and the single-crystalline nature of the solid may be preserved. Because of this photoactivation, time-resolved crystallography is often described as “photocrystallography”. The initial photocrystallographic studies were carried out on molecular complexes that either underwent irreversible photoactivated processes where the conversion took hours or days. Structural snapshots were taken during the process. Materials that achieved a metastable state under photoactivation and the excited (metastable) state had a long enough lifetime for the data from the crystal to be collected and the structure solved. For systems with shorter lifetimes, the first time-resolved results were obtained for macromolecular structures, where pulsed lasers were used to pump up the short lifetime excited state species and their structures were probed by using synchronised X-ray pulses from a high-intensity source. Developments in molecular crystallography soon followed, initially with monochromatic X-ray radiation, and pump-probe techniques were used to establish the structures of photoactivated molecules with lifetimes in the micro- to millisecond range. For molecules with even shorter lifetimes in the sub-microsecond range, Laue diffraction methods (rather than using monochromatic radiation) were employed to speed up the data collections and reduce crystal damage. Future developments in time-resolved crystallography are likely to involve the use of XFELs to complete “single-shot” time-resolved diffraction studies that are already proving successful in the macromolecular crystallographic field.</p