Feasibility of Tomotherapy-Based Image-Guided Radiotherapy to Reduce Aspiration Risk in Patients with Non-Laryngeal and Non-Pharyngeal Head and Neck Cancer

PURPOSE: The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk. RESULTS: Mean pharyngeal dose was 23.2 Gy for the whole group. Two patients (4.2%) developed trace aspiration following radiotherapy which resolved with swallowing therapy. At a median follow-up of 19 months (1-48 months), all patients were able to resume normal oral feeding without aspiration. CONCLUSION AND CLINICAL RELEVANCE: IGRT may reduce the aspiration risk by decreasing the mean pharyngeal dose in the presence of large cervical lymph nodes. Further prospective studies with IGRT should be performed in patients with non-laryngeal and non-hypopharyngeal head and neck cancers to verify this hypothesis

Changes in and predictors of length of stay in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England: a population-based

BACKGROUND Decreases in length of stay (LOS) in hospital after breast cancer surgery can be partly attributed to the change to less radical surgery, but many other factors are operating at the patient, surgeon and hospital levels. This study aimed to describe the changes in and predictors of length of stay (LOS) in hospital after surgery for breast cancer between 1997/98 and 2004/05 in two regions of England. METHODS Cases of female invasive breast cancer diagnosed in two English cancer registry regions were linked to Hospital Episode Statistics data for the period 1st April 1997 to 31st March 2005. A subset of records where women underwent mastectomy or breast conserving surgery (BCS) was extracted (n = 44,877). Variations in LOS over the study period were investigated. A multilevel model with patients clustered within surgical teams and NHS Trusts was used to examine associations between LOS and a range of factors. RESULTS Over the study period the proportion of women having a mastectomy reduced from 58% to 52%. The proportion varied from 14% to 80% according to NHS Trust. LOS decreased by 21% from 1997/98 to 2004/05 (LOSratio = 0.79, 95%CI 0.77-0.80). BCS was associated with 33% shorter hospital stays compared to mastectomy (LOSratio = 0.67, 95%CI 0.66-0.68). Older age, advanced disease, presence of comorbidities, lymph node excision and reconstructive surgery were associated with increased LOS. Significant variation remained amongst Trusts and surgical teams. CONCLUSION The number of days spent in hospital after breast cancer surgery has continued to decline for several decades. The change from mastectomy to BCS accounts for only 9% of the overall decrease in LOS. Other explanations include the adoption of new techniques and practices, such as sentinel lymph node biopsy and early discharge. This study has identified wide variation in practice with substantial cost implications for the NHS. Further work is required to explain this variation

The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster

The regulatory protein NsrR, a member of the Rrf2 family of transcription repressors, is specifically dedicated to sensing nitric oxide (NO) in a variety of pathogenic and non-pathogenic bacteria. It has been proposed that NO directly modulates NsrR activity by interacting with a predicted [Fe-S] cluster in the NsrR protein, but no experimental evidence has been published to support this hypothesis. Here we report the purification of NsrR from the obligate aerobe Streptomyces coelicolor. We demonstrate using UV-visible, near UV CD and EPR spectroscopy that the protein contains an NO-sensitive [2Fe-2S] cluster when purified from E. coli. Upon exposure of NsrR to NO, the cluster is nitrosylated, which results in the loss of DNA binding activity as detected by bandshift assays. Removal of the [2Fe-2S] cluster to generate apo-NsrR also resulted in loss of DNA binding activity. This is the first demonstration that NsrR contains an NO-sensitive [2Fe-2S] cluster that is required for DNA binding activity

Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Effects of protein–carbohydrate supplementation on immunity and resistance training outcomes: a double-blind, randomized, controlled clinical trial

Purpose: To examine the impact of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on resistance training outcomes, body composition, muscle thickness, blood indices of health and salivary human neutrophil peptides (HNP1-3), as reference of humoral immunity followed an 8-week resistance training program in college athletes. Methods: Twenty-seven recreationally physically active males and females (n = 9 per treatment) were randomly assigned to one of the three groups: hydrolyzed beef protein, whey protein, or non-protein isoenergetic carbohydrate. Treatment consisted of ingesting 20 g of supplement, mixed with orange juice, once a day immediately post-workout or before breakfast on non-training days. Measurements were performed pre- and post-intervention on total load (kg) lifted at the first and last workout, body composition (via plethysmography) vastus medialis thickness (mm) (via ultrasonography), and blood indices of health. Salivary HNP1-3 were determined before and after performing the first and last workout. Results: Salivary concentration and secretion rates of the HNP1-3 decreased in the beef condition only from pre-first-workout (1.90 ± 0.83 μg/mL; 2.95 ± 2.83 μg/min, respectively) to pre-last-workout (0.92 ± 0.63 μg/mL, p = 0.025, d = 1.03; 0.76 ± 0.74 μg/min, p = 0.049, d = 0.95), and post-last-workout (0.95 ± 0.60 μg/mL, p = 0.032, d = 1.00; 0.59 ± 0.52 μg/min, p = 0.027, d = 1.02). No other significant differences between groups were observed. Conclusions: Supplementation with a carbohydrate–protein beverage may support resistance training outcomes in a comparable way as the ingestion of only carbohydrate. Furthermore, the ingestion of 20 g of hydrolyzed beef protein resulted in a decreased level and secretion rates of the HNP1-3 from baseline with no negative effect on blood indices of health

Enteric-coated sodium bicarbonate supplementation improves high-intensity cycling performance in trained cyclists

Purpose: Enteric-coated sodium bicarbonate (NaHCO3) can attenuate gastrointestinal (GI) symptoms following acute bicarbonate loading, although the subsequent effects on exercise performance have not been investigated. The purpose of this study was to examine the effects of enteric-coated NaHCO3 supplementation on high-intensity exercise performance and GI symptoms. Methods: Eleven trained male cyclists completed three 4 km time trials after consuming; a placebo or 0.3 g∙kg–1 body mass NaHCO3 in enteric-coated or gelatin capsules. Exercise trials were timed with individual peak blood bicarbonate ion concentration ([HCO3–]). Blood acid–base balance was measured pre-ingestion, pre-exercise, and post-exercise, whereas GI symptoms were recorded pre-ingestion and immediately pre-exercise. Results: Pre-exercise blood [HCO3−] and potential hydrogen (pH) were greater for both NaHCO3 conditions (P &lt; 0.0005) when compared to placebo. Performance time was faster with enteric-coated (− 8.5 ± 9.6 s, P = 0.044) and gelatin (− 9.6 ± 7.2 s, P = 0.004) NaHCO3 compared to placebo, with no significant difference between conditions (mean difference = 1.1 ± 5.3 s, P = 1.000). Physiological responses were similar between conditions, although blood lactate ion concentration was higher with gelatin NaHCO3 (2.4 ± 1.7 mmol∙L–1, P = 0.003) compared with placebo. Furthermore, fewer participants experienced GI symptoms with enteric-coated (n = 3) compared to gelatin (n = 7) NaHCO3. Discussion: Acute enteric-coated NaHCO3 consumption mitigates GI symptoms at the onset of exercise and improves subsequent 4 km cycling TT performance. Athletes who experience GI side-effects after acute bicarbonate loading may, therefore, benefit from enteric-coated NaHCO3 supplementation prior to exercise performance.</p

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the Impact of NF1 on Quality Of Life (INF1-QOL) questionnaire

Background Neurofibromatosis 1 (NF1) is an inherited, multi-system, tumour suppressor disorder with variable complications that cause psychological distress and social isolation. The study aim was to develop and validate a disease-specific questionnaire to measure quality of life (QOL) in NF1 that is suitable both as an assessment tool in clinical practice and in clinical trials of novel therapy. Methods The Impact of NF1 on Quality of Life (INF1-QOL) questionnaire was developed by a literature search for common terms, focus group (n=6), semi-structured interviews (n=21), initial drafts (n =50) and final 14 item questionnaire (n=50). Bivariate correlations between items, exploratory factor analysis, correlations with severity and EuroQol were employed. Results INF1-QOL showed good internal reliability (Cronbach’s alpha 0.87), mean total INF1-QOL score was 8.64 (SD 6.3), median 7.00, range 0-30 (possible range 0-42); no significant correlations with age or gender. The mean total EuroQol score was 7.38 (SD 2.87), median 6.5, mean global EuroQol score was 76.34 (SD 16.56), median 80. Total INF1-QOL score correlated with total EuroQol r=0.82, p<0.0001. The highest impact on QOL was moderate or severe problems with anxiety and depression (32%) and negative effects of NF1 on role and outlook on life (42%). The mean inter-relater reliability for grading of clinical severity scores was 0.71 (range 0.65-0.79), and intra-class correlation was 0.92. The mean clinical severity score was 1.95 (SD 0.65) correlating r=0.34 with total INF1-QOL score p<0.05 and correlated 0.37 with total EuroQol score p<0.01. The clinical severity score was mild in 17 (34%), moderate in 16 (32%) and 17 (34%) individuals had severe disease. Conclusions INF1-QOL is a validated, reliable disease specific questionnaire that is easy and quick to complete. Role and outlook on life and anxiety and depression have the highest impact on QOL indicating the variability, severity and unpredictability of NF1. INFI-QOL correlates moderately with clinical severity. The moderate relationship between INF1-QOL and physician rated severity emphasizes the difference between clinical and patient perception. INFI-QOL will be useful in individual patient assessment and as an outcome measure for clinical trials

The utilisation of health research in policy-making: Concepts, examples and methods of assessment

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production