Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Evaluation of dog owners' perceptions concerning radiation therapy

<p>Abstract</p> <p>Background</p> <p>External radiation therapy (RT) has been available for small animals in Sweden since 2006. This study was designed to obtain information on owner experiences and perceptions related to RT of cancer in their dogs. Another survey was used to determine the attitudes about use of RT in a group of Swedish veterinarians. Their responses were analyzed and compared to their level of knowledge of oncology and RT.</p> <p>Methods</p> <p>Owners of all dogs (n = 23) who had undergone RT for malignancy at Jönköping Small Animal Hospital between March 2006 to September 2007 were interviewed. A questionnaire was given to a selected group of veterinarians.</p> <p>Results</p> <p>All 23 owners responded. All owners thought that their dog did well during RT and most that their dog was also fine during the following phase when acute RT-related skin reactions occur and heal. Three owners stated that their dog had pain that negatively impacted quality of life because of radiation dermatitis. Five owners reported that RT positively impacted quality of life of the dog during the first weeks after RT because palliation was achieved. The owners were not disturbed by the efforts required of them. All but one owner (22 of 23) stated that they would make the same decision about RT again if a similar situation occurred. The most important factor for this decision was the chance to delay occurrence of tumour-related discomfort. The chance for cure was of less importance but still essential, followed by expected side effects. Time commitments, travel, number of treatments required and financial cost; all had low impact. The veterinarian survey showed that less background knowledge of small animal oncology/RT was associated with more negative expectations of RT for small animals.</p> <p>Conclusion</p> <p>The results show that for these owners, RT was a worthwhile treatment modality and that the discomfort for the dog was manageable and acceptable relative to the benefits. Improved continuing education about small animal RT in Sweden will likely result in increased evidence-based and positive treatment recommendations concerning RT by veterinarians.</p

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Sequence variation in the human transcription factor gene POU5F1

<p>Abstract</p> <p>Background</p> <p>POU5F1 expression is required to maintain stem cell pluripotency and for primordial germ cells to retain proliferative capability in embryonic development. Recent evidence suggests that <it>POU5F1 </it>may also be a testicular germ cell carcinoma (TGCC) oncogene, and <it>POU5F1 </it>variation may influence TGCC risk. As an important first step to a genetic association study, we sought to identify all common sequence variants in an 11.3 kb region containing <it>POU5F1</it>, and to describe the linkage disequilibrium patterns, using DNA from individuals of African-descent (AD) and European-descent (ED).</p> <p>Results</p> <p>A higher number of polymorphisms was observed in the AD (n = 102) versus ED (n = 82) population. Among the 41 observed haplotypes, 21 (51%) and 12 (29%) were unique to the AD and ED populations, respectively, while 8 (20%) were observed in both. The number of tagging polymorphisms necessary to explain at least 80% of common variation (minor allele frequency ≥ 0.10) due to the remaining untyped polymorphisms was 17 for an AD and 10 for an ED population, providing a 4.0- and 7.0-fold gain in genotyping efficiency for characterizing nucleotide variation, respectively.</p> <p>Conclusion</p> <p><it>POU5F1 </it>is highly polymorphic, however a smaller subset of polymorphisms can tag the observed genetic variation with little loss of information.</p

Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation

Background. We previously reported the in vitro spontaneous transformation of human mesenchymal stem cells (MSC) generating a population with tumorigenic potential, that we termed transformed mesenchymal cells (TMC). Methodology/Principal Findings. Here we have characterized the molecular changes associated with TMC generation. Using microarrays techniques we identified a set of altered pathways and a greater number of downregulated than upregulated genes during MSC transformation, in part due to the expression of many untranslated RNAs in MSC. Microarray results were validated by qRT-PCR and protein detection. Conclusions/Significance. In our model, the transformation process takes place through two sequential steps; first MSC bypass senescence by upregulating c-myc and repressing p16 levels. The cells then bypass cell crisis with acquisition of telomerase activity, Ink4a/Arf locus deletion and Rb hyperphosphorylation. Other transformation-associated changes include modulation of mitochondrial metabolism, DNA damage-repair proteins and cell cycle regulators. In this work we have characterized the molecular mechanisms implicated in TMC generation and we propose a two-stage model by which a human MSC becomes a tumor cell

The Road Less Traveled: Regulation of Leukocyte Migration Across Vascular and Lymphatic Endothelium by Galectins

Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood to the lymph node. The proteins and cellular interactions which regulate leukocyte migration across the vascular endothelium are well studied; however, little is known about the factors that regulate leukocyte migration across the lymphatic endothelium. Here, we will summarize evidence for a role for galectins, a family of carbohydrate-binding proteins, in regulating leukocyte migration across the vascular endothelium and propose that galectins are also involved in leukocyte migration across the lymphatic endothelium

A Communal Bacterial Adhesin Anchors Biofilm and Bystander Cells to Surfaces

While the exopolysaccharide component of the biofilm matrix has been intensively studied, much less is known about matrix-associated proteins. To better understand the role of these proteins, we undertook a proteomic analysis of the V. cholerae biofilm matrix. Here we show that the two matrix-associated proteins, Bap1 and RbmA, perform distinct roles in the biofilm matrix. RbmA strengthens intercellular attachments. In contrast, Bap1 is concentrated on surfaces where it serves to anchor the biofilm and recruit cells not yet committed to the sessile lifestyle. This is the first example of a biofilm-derived, communally synthesized conditioning film that stabilizes the association of multilayer biofilms with a surface and facilitates recruitment of planktonic bystanders to the substratum. These studies define a novel paradigm for spatial and functional differentiation of proteins in the biofilm matrix and provide evidence for bacterial cooperation in maintenance and expansion of the multilayer biofilm

Suicide attempts and related factors in patients admitted to a general hospital: a ten-year cross-sectional study (1997-2007)

[Abstract] Background: Suicide and suicide attempts represent a severe problem for public health services. The aim of this study is to determine the socio-demographic and psychopathological variables associated with suicide attempts in the population admitted to a General Hospital. Methods: An observational-descriptive study of patients admitted to the A Coruña University Hospital (Spain) during the period 1997-2007, assessed by the Consultation and Liaison Psychiatric Unit. We include n = 5,234 admissions from 4,509 patients. Among these admissions, n = 361 (6.9%) were subsequent to a suicide attempt. Admissions arising from a suicide attempt were compared with admissions occurring due to other reasons.Multivariate generalised estimating equation logistic regression models were used to examine factors associated with suicide attempts. Results: Adjusting by age, gender, educational level, cohabitation status, being employed or unemployed, the psychiatric diagnosis at the time of the interview and the information on previous suicide attempts, we found that the variables associated with the risk of a suicide attempt were: age, psychiatric diagnosis and previous suicide attempts. The risk of suicide attempts decreases with age (OR = 0.969). Psychiatric diagnosis was associated with a higher risk of suicide attempts, with the highest risk being found for Mood or Affective Disorders (OR = 7.49), followed by Personality Disorders (OR = 7.31), and Schizophrenia and Other Psychotic Disorders (OR = 5.03).The strongest single predictive factor for suicide attempts was a prior history of attempts (OR = 23.63). Conclusions: Age, psychopathological diagnosis and previous suicide attempts are determinants of suicide attempts

Suicidality in primary care patients who present with sadness and anhedonia: a prospective European study

Background: Sadness and anhedonia (loss of interest in activities) are central symptoms of major depression. However, not all people with these symptoms meet diagnostic criteria for major depression. We aimed to assess the importance of suicidality in the outcomes for primary care patients who present with sadness and anhedonia. Method: Cohort study of 2,599 unselected primary care attenders in six European countries followed up at 6 and 12 months. Results: 1) In patients with sadness and/or anhedonia who were not depressed at entry to the study, suicide plans (OR = 3.05; 95 % CI = 1.50–6.24; p = 0.0022) and suicide attempts (OR = 9.08; 95 % CI = 2.57–32.03; p = 0.0006) were significant predictors of developing new onset depression at 6 or 12 months. 2) In patients with sadness and/or anhedonia who met CIDI criteria for major depression at entry, suicidal ideation (OR = 2.93; 95 % CI = 1.70–5.07; p = 0.0001), suicide plans (OR = 3.70; 95 % CI = 2.08–6.57; p < 0.0001), and suicide attempts (OR = 3.33; 95 % CI = 1.47–7.54; p = 0.0040) were significant predictors of persistent depression at 6 or 12 months. Conclusions: Three questions on suicidality could help primary care professionals to assess such patients more closely without necessarily establishing whether they meet criteria for major depression.This research was funded by a grant from The European Commission, referencePREDICT-QL4-CT2002-00683. We are also grateful for part support in Europe from: the Estonian Scientific Foundation (grant number 5696); the Slovenian Ministry for Research (grant No.4369-1027); the Spanish Ministry of Health (grant FIS references: PI041980, PI041771, PI042450) and the Spanish Network of Primary Care Research, redIAPP (ISCIII-RETICS RD06/0018) and SAMSERAP group; and the UK NHS Research and Development office for providing service support costs in the UK. We are also grateful for the support from the University of Malaga (Spain) and to Carlos García from Loyola Andalucía University (Spain)