Acute-phase inter-alpha-trypsin inhibitor heavy chain 4 levels in serum and milk of cows with subclinical mastitis caused by Streptococcus species and coagulase-negative Staphylococcus species

The aim of the study was to investigate the concentrations of acute-phase inter-a-trypsin inhibitor heavy chain 4 (ITIH4) in serum and milk of cows with subclinical mastitis caused by Streptococcus sp. (STR) and coagulase-negative Staphylococcus sp. (CNS) and healthy cows. The blood and milk samples were obtained from 60 mid-lactation, multiparous Holstein-Friesian cows from 7 herds in the Lublin region of Poland. In the milk samples from 40 cows with subclinical mastitis, Streptococcus sp. and CNS were isolated. The ITIH4 was significantly higher in serum of cows with subclinical mastitis caused both by STR and CNS compared with healthy cows. One hundred percent of animals infected with Streptococcus sp. and 89% of animals infected with Staphylococcus sp. showed ITIH4 concentration in sera higher than 0.5 mg/mL. The concentration of ITIH4 in milk also was significantly higher in cows with subclinical mastitis caused by Streptococcus sp. and Staphylococcus sp. compared with the control group. Seventy percent of cows infected by STR and CNS showed ITIH4 concentration in milk higher than 2.5 µg/mL. Milk ITIH4 concentration higher than 5 µg/mL was found in 55% of animals infected with Streptococcus sp. and in 40% of animals infected with Staphylococcus sp. No statistically significant differences were observed in ITIH4 concentrations both in serum and in milk between the studied unhealthy animal groups. These results suggest that ITIH4 may be used in the future as a novel diagnostic marker in serum and in milk of subclinical mastitis in cows

Comparative proteomics of exosomes secreted by tumoral jurkat t cells and normal human t cell blasts unravels a potential tumorigenic role for valosin-containing protein

We have previously characterized that FasL and Apo2L/TRAIL are stored in their bioactive form inside human T cell blasts in intraluminal vesicles present in multivesicular bodies. These vesicles are rapidly released to the supernatant in the form of exosomes upon re-activation of T cells. In this study we have compared for the first time proteomics of exosomes produced by normal human T cell blasts with those produced by tumoral Jurkat cells, with the objective of identify proteins associated with tumoral exosomes that could have a previously unrecognized role in malignancy. We have identified 359 and 418 proteins in exosomes from T cell blasts and Jurkat cells, respectively. Interestingly, only 145 (around a 40%) are common. The major proteins in both cases are actin and tubulin isoforms and the common interaction nodes correspond to these cytoskeleton and related proteins, as well as to ribosomal and mRNA granule proteins. We detected 14 membrane proteins that were especially enriched in exosomes from Jurkat cells as compared with T cell blasts. The most abundant of these proteins was valosin-containing protein (VCP), a membrane ATPase involved in ER homeostasis and ubiquitination. In this work, we also show that leukemic cells are more sensitive to cell death induced by the VCP inhibitor DBeQ than normal T cells. Furthermore, VCP inhibition prevents functional exosome secretion only in Jurkat cells, but not in T cell blasts. These results suggest VCP targeting as a new selective pathway to exploit in cancer treatment to prevent tumoral exosome secretion

Characterization of human mesenchymal stem cells from Ewing sarcoma patients. Pathogenetic implications

Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin

Avalanche dynamics, surface roughening and self-organized criticality - experiments on a 3 dimensional pile of rice

We present a two-dimensional system which exhibits features of self-organized criticality. The avalanches which occur on the surface of a pile of rice are found to exhibit finite size scaling in their probability distribution. The critical exponents are $\tau$ = 1.21(2) for the avalanche size distribution and $D$ = 1.99(2) for the cut-off size. Furthermore the geometry of the avalanches is studied leading to a fractal dimension of the active sites of $d_B$ = 1.58(2). Using a set of scaling relations, we can calculate the roughness exponent $\alpha = D - d_B$ = 0.41(3) and the dynamic exponent $z = D(2 - \tau)$ = 1.56(8). This result is compared with that obtained from a power spectrum analysis of the surface roughness, which yields $\alpha$ = 0.42(3) and $z$ = 1.5(1) in excellent agreement with those obtained from the scaling relations.Comment: 7 pages, 8 figures, accepted for publication in PR

Critical behavior of a one-dimensional fixed-energy stochastic sandpile

We study a one-dimensional fixed-energy version (that is, with no input or loss of particles), of Manna's stochastic sandpile model. The system has a continuous transition to an absorbing state at a critical value $\zeta_c$ of the particle density. Critical exponents are obtained from extensive simulations, which treat both stationary and transient properties. In contrast with other one-dimensional sandpiles, the model appears to exhibit finite-size scaling, though anomalies exist in the scaling of relaxation times and in the approach to the stationary state. The latter appear to depend strongly on the nature of the initial configuration. The critical exponents differ from those expected at a linear interface depinning transition in a medium with point disorder, and from those of directed percolation.Comment: 15 pages, 11 figure

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation

We report a case of a 13-year-old girl with soft tissue sarcoma of the hand, which showed muscle and neuroectodermal immunophenotypes. Molecular studies were performed on RNA collected from fine-needle aspiration (FNA) cytology and peripheral blood samples by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. This biphenotypic tumor showed simultaneous expression of EWS-FLI1 and PAX3-FKHR transcripts, specific of Ewing family tumors and alveolar rhabdomyosarcoma, respectively. Although childhood sarcomas with simultaneous muscle and neural differentiation have been described to have EWS-FLI1 transcripts, there are no reports of tumors with both transcripts. Cytological specimens are a good source of RNA for molecular studie

An intervention to support adherence to inhaled medication in adults with cystic fibrosis : the ACtiF research programme including RCT

Background People with cystic fibrosis frequently have low levels of adherence to inhaled medications. Objectives The objectives were to develop and evaluate an intervention for adults with cystic fibrosis to improve adherence to their inhaled medication. Design We used agile software methods to develop an online platform. We used mixed methods to develop a behaviour change intervention for delivery by an interventionist. These were integrated to become the CFHealthHub intervention. We undertook a feasibility study consisting of a pilot randomised controlled trial and process evaluation in two cystic fibrosis centres. We evaluated the intervention using an open-label, parallel-group randomised controlled trial with usual care as the control. Participants were randomised in a 1 : 1 ratio to intervention or usual care. Usual care consisted of clinic visits every 3 months. We undertook a process evaluation alongside the randomised controlled trial, including a fidelity study, a qualitative interview study and a mediation analysis. We undertook a health economic analysis using both a within-trial and model-based analysis. Setting The randomised controlled trial took place in 19 UK cystic fibrosis centres. Participants Participants were people aged ≥ 16 years with cystic fibrosis, on the cystic fibrosis registry, not post lung transplant or on the active transplant list, who were able to consent and not using dry-powder inhalers. Intervention People with cystic fibrosis used a nebuliser with electronic monitoring capabilities. This transferred data automatically to a digital platform. People with cystic fibrosis and clinicians could monitor adherence using these data, including through a mobile application (app). CFHealthHub displayed graphs of adherence data as well as educational and problem-solving information. A trained interventionist helped people with cystic fibrosis to address their adherence. Main outcome measures Randomised controlled trial – adjusted incidence rate ratio of pulmonary exacerbations meeting the modified Fuchs criteria over a 12-month follow-up period (primary outcome); change in percentage adherence; and per cent predicted forced expiratory volume in 1 second (key secondary outcomes). Process evaluation – percentage fidelity to intervention delivery, and participant and interventionist perceptions of the intervention. Economic modelling – incremental cost per quality-adjusted life-year gained. Results Randomised controlled trial – 608 participants were randomised to the intervention (n = 305) or usual care (n = 303). To our knowledge, this was the largest randomised controlled trial in cystic fibrosis undertaken in the UK. The adjusted rate of exacerbations per year (primary outcome) was 1.63 in the intervention and 1.77 in the usual-care arm (incidence rate ratio 0.96, 95% confidence interval 0.83 to 1.12; p = 0.638) after adjustment for covariates. The adjusted difference in mean weekly normative adherence was 9.5% (95% confidence interval 8.6% to 10.4%) across 1 year, favouring the intervention. Adjusted mean difference in forced expiratory volume in 1 second (per cent) predicted at 12 months was 1.4% (95% confidence interval –0.2% to 3.0%). No adverse events were related to the intervention. Process evaluation – fidelity of intervention delivery was high, the intervention was acceptable to people with cystic fibrosis, participants engaged with the intervention [287/305 (94%) attended the first intervention visit], expected mechanisms of action were identified and contextual factors varied between randomised controlled trial sites. Qualitative interviews with 22 people with cystic fibrosis and 26 interventionists identified that people with cystic fibrosis welcomed the objective adherence data as proof of actions to self and others, and valued the relationship that they built with the interventionists. Economic modelling – the within-trial analysis suggests that the intervention generated 0.01 additional quality-adjusted life-years at an additional cost of £865.91 per patient, leading to an incremental cost-effectiveness ratio of £71,136 per quality-adjusted life-year gained. This should be interpreted with caution owing to the short time horizon. The health economic model suggests that the intervention is expected to generate 0.17 additional quality-adjusted life-years and cost savings of £1790 over a lifetime (70-year) horizon; hence, the intervention is expected to dominate usual care. Assuming a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, the probability that the intervention generates more net benefit than usual care is 0.89. The model results are dependent on assumptions regarding the duration over which costs and effects of the intervention apply, the impact of the intervention on forced expiratory volume in 1 second (per cent) predicted and the relationship between increased adherence and drug-prescribing levels. Limitations Number of exacerbations is a sensitive and valid measure of clinical change used in many trials. However, data collection of this outcome in this context was challenging and could have been subject to bias. It was not possible to measure baseline adherence accurately. It was not possible to quantify the impact of the intervention on the number of packs of medicines prescribed. Conclusions We developed a feasible and acceptable intervention that was delivered to fidelity in the randomised controlled trial. We observed no statistically significant difference in the primary outcome of exacerbation rates over 12 months. We observed an increase in normative adherence levels in a disease where adherence levels are low. The magnitude of the increase in adherence may not have been large enough to affect exacerbations. Future work Given the non-significant difference in the primary outcome, further research is required to explore why an increase in objective normative adherence did not reduce exacerbations and to develop interventions that reduce exacerbations. Trial registration Work package 3.1: Current Controlled Trials ISRCTN13076797. Work packages 3.2 and 3.3: Current Controlled Trials ISRCTN55504164

Characterizing the invasive tumor front of aggressive uterine adenocarcinoma and leiomyosarcoma

The invasive tumor front (the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors

Interaction of engineered surfaces with the living world: Ion implantation vs. osseointegration

The reaction of living tissues to foreign materials is a highly complex process that currently is insufficiently understood. Nevertheless, if specific reactions are to be promoted, this understanding is highly valuable and thus a significant research effort is being devoted to this issue. Typically, when a biomaterial is inserted in living tissue, proteins and other bio-molecules will adsorb to the surface. As this protein layer will mediate the interaction of the biomaterial with the living world, the consequent reactions will be highly dependant on this very first stage. Furthermore, different materials, i.e. surfaces, typically elicit a very different tissue response. It is commonly admitted that the primary adsorption depends heavily on the surface chemistry, surface topography and surface physical characteristics. Interactions between surface micro-topography and living cells have been widely studied, but protein specific reactions versus nano-topography have been barely explored. Ion beam modification of surfaces, which affect these key properties, can therefore be (i) a powerful tool to advance in the understanding of these nanoscale phenomena and (ii) useful as an industrial treatment of high value added medical devices. This work will explore the application of ion beam based surface treatments to cause specific reactions in hard tissue regeneration. A variety of in vitro and in vivo results are presented corresponding to ion implantation treatments promoting '' osseointegration '' or intimate binding between the biomaterial and the living tissue, without any soft tissue interlayer, and an overview of the mechanism behind is offered, i.e. among other behaviour of osteoblasts, signalling proteins as the integrins, nanotopographic parameters.Basque Government, Department of Industry, project ref. IC-2004/0027900

Emergence of permanent teeth in Tanzanian children.

Item does not contain fulltextOBJECTIVE: The aim of the present study was to investigate the emergence of permanent teeth among Tanzanian children. METHODS: A total of 869 Tanzanian children were recruited from 16 schools in age groups 3.5-5, 6.5-8, 9.5-11 and 15-16 years of whom 428 (49%) were boys and 441 (51%) were girls. The effects of age and gender on the emergence stages of the dentition were determined for the four age groups. RESULTS: Girls, but not boys, had some permanent maxillary canines, second premolars and mandibular and maxillary second molars as early as at the age of 6.5-8 years. Permanent teeth of both the first and the second transitional periods were already emerging at the age of 3.5-5 years and 6.5-8 years, respectively. At 3.5-5 years, 9% of the permanent teeth belonging to the first transitional period were already in occlusion. Emergence of incisors and first molars was more advanced in girls than in boys in age groups 3.5-5 and 6.5-8 years. CONCLUSIONS: Parallel to earlier reports on different ethnic groups, the results of this study indicate that the permanent teeth of Tanzanian children erupt earlier in girls than in boys, and the mandibular teeth erupt earlier than the corresponding maxillary teeth. The difference between boys and girls was found in both the first and second transitional period. Permanent teeth in Tanzanian children clearly emerge earlier than in Caucasian children