The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection

Evaluation of the tissue toxicity of antiseptics by the hen's egg test on the chorioallantoic membrane (HETCAM)

<p>Abstract</p> <p>Background</p> <p>Antiseptics are frequently used for the prophylaxis and treatment of local infections of chronic wounds. Whereas local antiseptics in general have a positive effect on wound healing an uncritical use may impair wound healing due to toxic side effects.</p> <p>Objective</p> <p>We sought to assess the vascular irritation potential of different antiseptic solutions and ointments commonly used for short and long term application as a measure of tissue toxicity.</p> <p>Method</p> <p>The vascular irritation was evaluated by the hen's egg test (HET) on the chorioallantoic membrane (CAM). The effects on the vessels of a mucous membrane were directly assessed by stereomicroscopic observation in vivo.</p> <p>Results</p> <p>Severe CAM irritation was observed after short-term applications of 1% octenidin-2HCl (Octeni sept™), 72% isopropanol (Cutasept™), 0.35% chloroxylenol (Dettol™) and 10% PVP-I ointment (Betaisodona™). Medium irritations were observed for 10% PVP-I solution (Betaisodona™), 3% lysosomal PVP-I ointment (Repithel™), 1.8% cadexomer-iodine ointment (Iodosorb™) and 1% cadexomer-iodine pellets (Iodosorb™). Finally, slight irritations were observed for 1% PVP-I solution (Betaisodona™), 0.1% polyhexanid plus betain (Prontosan™) and 1% silver-sulfadiazine ointment (Flammazine™), whereas 0.04% polyhexanid solution (Lavanid™), washings from sterile maggots of Lucilia sericata and filtrated enzymes from Clostridium histolyticum (Iruxol-N™) showed no effects of irritation. In the long-term approaches, no vascular irritations were found for polyhexanid, washings from Lucilia sericata and enzyme filtrations from Clostridium histolyticum.</p> <p>Conclusion</p> <p>The vascular injuries caused by the studied antiseptics are an indirect indicator of their tissue toxicity. Strikingly, even therapeutic substances, which have been regarded as safe in their application for the treatment of chronic wounds in clinical studies, showed severe irritations on the CAM. We suggest that agents with no or low irritation potential on the CAM should be preferred in the clinical practice in order to obtain optimal results.</p

Psychosocial risk factors for suicidality in children and adolescents

Suicidality in childhood and adolescence is of increasing concern. The aim of this paper was to review the published literature identifying key psychosocial risk factors for suicidality in the paediatric population. A systematic two-step search was carried out following the PRISMA statement guidelines, using the terms 'suicidality, suicide, and self-harm' combined with terms 'infant, child, adolescent' according to the US National Library of Medicine and the National Institutes of Health classification of ages. Forty-four studies were included in the qualitative synthesis. The review identified three main factors that appear to increase the risk of suicidality: psychological factors (depression, anxiety, previous suicide attempt, drug and alcohol use, and other comorbid psychiatric disorders); stressful life events (family problems and peer conflicts); and personality traits (such as neuroticism and impulsivity). The evidence highlights the complexity of suicidality and points towards an interaction of factors contributing to suicidal behaviour. More information is needed to understand the complex relationship between risk factors for suicidality. Prospective studies with adequate sample sizes are needed to investigate these multiple variables of risk concurrently and over time

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10−7) in SOX2OT and rs17030795 (P=5.84×10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10−6) between CUL3 and FAM124B and rs1886797 (P=8.05×10−6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P= 4×10−6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

PLoS One

Age-related macular degeneration (AMD) is a common, progressive multifactorial vision-threatening disease and many genetic and environmental risk factors have been identified. The risk of AMD is influenced by lifestyle and diet, which may be reflected by an altered metabolic profile. Therefore, measurements of metabolites could identify biomarkers for AMD, and could aid in identifying high-risk individuals. Hypothesis-free technologies such as metabolomics have a great potential to uncover biomarkers or pathways that contribute to disease pathophysiology. To date, only a limited number of metabolomic studies have been performed in AMD. Here, we aim to contribute to the discovery of novel biomarkers and metabolic pathways for AMD using a targeted metabolomics approach of 188 metabolites. This study focuses on non-advanced AMD, since there is a need for biomarkers for the early stages of disease before severe visual loss has occurred. Targeted metabolomics was performed in 72 patients with early or intermediate AMD and 72 control individuals, and metabolites predictive for AMD were identified by a sparse partial least squares discriminant analysis. In our cohort, we identified four metabolite variables that were most predictive for early and intermediate stages of AMD. Increased glutamine and phosphatidylcholine diacyl C28:1 levels were detected in non-advanced AMD cases compared to controls, while the rate of glutaminolysis and the glutamine to glutamate ratio were reduced in non-advanced AMD. The association of glutamine with non-advanced AMD corroborates a recent report demonstrating an elevated glutamine level in early AMD using a different metabolomics technique. In conclusion, this study indicates that metabolomics is a suitable method for the discovery of biomarker candidates for AMD. In the future, larger metabolomics studies could add to the discovery of novel biomarkers in yet unknown AMD pathways and expand our insights in AMD pathophysiology

La teoría de la relevancia y la estrategia humorística de la incongruencia-resolución

En la teoría de la Relevancia Sperber y Wilson proponen un modelo cognitivo de la interpretación humana basado en el interés del receptor por adquirir, en cada estadio de la conversación, la información más relevante Esta elección está influida, en última instancia, por un equilibrio entre interés y esfuerzo. En el presente artículo se propone una posible aplicación de esta teoría a la estrategia humorística de la "disonancia cognitiva", concretamente la estrategia de incongruencia-resolución, de tal modo que podemos encontrar una explicación de cómo el emisor consigue el efecto humorístico deseado.In Relevance theory Sperber and Wilson propose a cognitive model of human interpretation based on the addressee's willingness to grasp, in every step of the conversation the most relevant information. This choice is influenced, eventually, by a balance of interest and effort. In the present article we propose an application of this theory to the humorous strategy of "cognitive dissonance", specifically the strategy of incongruence-resolution, in such a way that we can find an explanation of how the addresser manages to get the desired humorous effect