Association of toxic indoor air with multi-organ symptoms in pupils attending a moisture-damaged school in Finland

Background: There is an on-going debate on how best to test toxic indoor air. Toxicological methods based on condensed water samples and cell culture technique are newly introduced research tools which were tested in this study. Methods: Pupils (n=47) from a water-damaged and (n=56) healthy schools were interviewed using a questionnaire. Indoor air was collected with a novel condensed water sampling technique and human THP-1 macrophages were exposed to the condensate. The cytotoxicity of cotton wool swab samples was tested using human BJ fibroblasts. Conventional microbiological culture methods were also performed. Results: Gastrointestinal problems (GI) were reported by 51% from the study cohort but only 4% of the control cohort, relative risk RR=14.30. For any neurological or neuropsychological symptoms, the RR was 63.04, muscular-skeletal pain RR=58.28, headache RR=31.00, respiratory symptoms RR=22.64, fatigue RR=21.45, sub febrility RR=15.49, ear infections RR=7.74, skin rash RR=5.96, all being statistically significant (P<0.001). All indoor air (n=7) and cotton wool samples (n=2) taken from the water-damaged classroom or in proximity of the problematic classrooms were toxic in cell culture assays. Low numbers of moisture-damage indicators were recovered from wall, passive air, and swab samples, namely Aspergillus ochraceus species group, Aspergillus, Eurotium species group, Fusarium, Tritirachium, Scopulariopsis genus group and Aspergillus versicolores species group. Conclusions: Indoor air toxicity and dampness-related microbiota recovered from the classrooms were associated with multi-organ morbidity of the school occupants. These results corroborated our previous reports from two adult cohorts i.e. evidence of causality. These new toxicological methods based on condensed water and cell culturing techniques seem to be superior to conventional microbiological methods in correlating with clinical symptoms

What Makes a 97-Year-Old Man Cycle 5,000 km a Year?

Background: The nature versus nurture debate is one of the oldest issues in the study of longevity, health and successful aging. Objective: We present a 97-year-old man (I.K.) as an example of the effects of habitual exercise on the aging process. Methods: Extensive assessments included medical examinations, interviews, musculoskeletal structure, performance characteristics, cognitive function and gut microbiota composition. Results: I.K. suffers from iatrogenic hypogonadism, prostate cancer, hypothyroidism and a history of deep popliteal thrombosis. Notwithstanding, he cycles up to 5,000 km a year and participates in competitive sports. His musculoskeletal properties, athletic performance, cognitive function and gut microbiota are outstanding. Some traits even exceed those seen in middle-aged men. Conclusions: His long-term physically and intellectually active lifestyles combined with extensive social interactions have most likely contributed to his exercise capacity, despite his medical history

5-α reductase inhibitors and prostate cancer prevention: where do we turn now?

With the lifetime risk of being diagnosed with prostate cancer so great, an effective chemopreventive agent could have a profound impact on the lives of men. Despite decades of searching for such an agent, physicians still do not have an approved drug to offer their patients. In this article, we outline current strategies for preventing prostate cancer in general, with a focus on the 5-α-reductase inhibitors (5-ARIs) finasteride and dutasteride. We discuss the two landmark randomized, controlled trials of finasteride and dutasteride, highlighting the controversies stemming from the results, and address the issue of 5-ARI use, including reasons why providers may be hesitant to use these agents for chemoprevention. We further discuss the recent US Food and Drug Administration ruling against the proposed new indication for dutasteride and the change to the labeling of finasteride, both of which were intended to permit physicians to use the drugs for chemoprevention. Finally, we discuss future directions for 5-ARI research

Global metabolomic profiling of uterine leiomyomas

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.Peer reviewe

Non-Hodgkin lymphoma response evaluation with MRI texture classification

<p>Abstract</p> <p>Background</p> <p>To show magnetic resonance imaging (MRI) texture appearance change in non-Hodgkin lymphoma (NHL) during treatment with response controlled by quantitative volume analysis.</p> <p>Methods</p> <p>A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests.</p> <p>Results</p> <p>NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images.</p> <p>Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue.</p> <p>Conclusion</p> <p>Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring.</p

Effect of dietary intervention on serum lignan levels in pregnant women - a controlled trial

<p>Abstract</p> <p>Background</p> <p>Mother's diet during pregnancy is important, since plant lignans and their metabolites, converted by the intestinal microflora to enterolignans, are proposed to possess multiple health benefits. Aim of our study was to investigate whether a dietary intervention affects lignan concentrations in the serum of pregnant women.</p> <p>Methods</p> <p>A controlled dietary intervention trial including 105 first-time pregnant women was conducted in three intervention and three control maternity health clinics. The intervention included individual counseling on diet and on physical activity, while the controls received conventional care. Blood samples were collected on gestation weeks 8-9 (baseline) and 36-37 (end of intervention). The serum levels of the plant lignans 7-hydroxymatairesinol, secoisolariciresinol, matairesinol, lariciresinol, cyclolariciresinol, and pinoresinol, and of the enterolignans 7-hydroxyenterolactone, enterodiol, and enterolactone, were measured using a validated method.</p> <p>Results</p> <p>The baseline levels of enterolactone, enterodiol and the sum of lignans were higher in the control group, whereas at the end of the trial their levels were higher in the intervention group. The adjusted mean differences between the baseline and end of the intervention for enterolactone and the total lignan intake were 1.6 ng/ml (p = 0.018, 95% CI 1.1-2.3) and 1.4 ng/mg (p = 0.08, 95% CI 1.0-1.9) higher in the intervention group than in the controls. Further adjustment for dietary components did not change these associations.</p> <p>Conclusion</p> <p>The dietary intervention was successful in increasing the intake of lignan-rich food products, the fiber consumption and consequently the plasma levels of lignans in pregnant women.</p> <p>Trial registration</p> <p><b>ISRCTN21512277, <url>http://www.isrctn.org</url></b></p

Identification of Estrogen Receptor Dimer Selective Ligands Reveals Growth-Inhibitory Effects on Cells That Co-Express ERα and ERβ

Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA) to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ