Environmental and lifestyle risk factors of breast cancer in Malta-a retrospective case-control study

The funding for this research was obtained as part of IMaGenX – and ItaliaMalta co-financed EU project Operational Programme 2007–2013.AIM AND BACKGROUND: Environmental exposures are known to play a role in the development of cancer, including breast cancer. There are known associations of breast cancer with environmental factors such as sunlight exposure, diet and exercise and alcohol consumption as well as physiological factors. This study examines the prevalence of risk factors for breast cancer related to dietary intake, environment and lifestyle in the female population of Malta. Malta has had little research in this area, and therefore an exploratory study was carried out. METHODS: A retrospective case-control design was applied. Two hundred cases and 403 controls were included. Both cases and controls were subjects without a known family history for breast cancer. Controls were age-matched to cases in an age-decade category roughly at a 2:1 ratio. Interviews were carried out face-to-face using a questionnaire designed by Maltese and Sicilian researchers, encompassing various factors including diet, lifestyle, physiological factors and medical history. Breast cancer risk was then analysed using both univariate and multivariate analyses. For factors having a metric scale, the Mann-Whitney test was used to compare mean scores, while for categorical factors, the chi-square test was used to compare percentages between the case and control groups. Statistical modelling was carried out using binary logistic regression to relate the likelihood of breast cancer to over 50 risk/protective factors analysed collectively. RESULTS: Univariate analysis showed around 20 parameters of interest, 14 of which were statistically significant at a 0.05 level of significance. Logistic regression analysis identified 11 predictors of interest that were statistically significant. Tomato, coffee and canned meat consumption were associated with lower likelihood of breast cancer (OR = 0.988, 0.901, 0.892, respectively), whereas beans and cabbage consumption and low sodium salt were positively associated with breast cancer (OR = 1.045, 1.834, 1.028, respectively). Premenopausal status was associated with a lower risk of breast cancer compared to postmenopausal status (OR = 0.067). Not having experienced myocardial infarction was associated with lower odds of breast cancer (OR = 0.331). Increased height was also found to have a strong association with risk of breast cancer, with the odds of having breast cancer increasing for every centimetre increase in height (OR = 1.048). In terms of quantity, odds of having breast cancer were lower in those exposed to sunlight (OR = 0.891). The odds of having breast cancer were also lower in those not using the oral contraceptive pill (OR = 0.454). CONCLUSIONS: Various factors in this exploratory study were found to be associated with development of breast cancer. While causal conclusions cannot be made, tomato consumption is of particular interest, as these results corroborate findings found in other studies. A negative association of breast cancer with sunlight exposure and oral contraceptive pill use corroborates findings in other studies. Other associations with dietary intake can be explained by dietary changes. More robust studies in this area, including possible longitudinal studies, are warranted.peer-reviewe

The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre treatment needle core biopsy and postanthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) p, h and a, catalase and manganese superoxide dismutase. GST p (P¼0.05) and catalase (P¼0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P¼0.017) and thioredoxin reductase (P¼0.022) were independent prognostic factors for distant metastasis free survival and TxNIP for overall survival (P¼0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P¼0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments

Cervicogenic headache caused by myofascial trigger points in the sternocleidomastoid: a case report

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74754/1/j.1468-2982.2007.01296.x.pd

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

Discrepancy between prevalence and perceived effectiveness of treatment methods in myofascial pain syndrome: Results of a cross-sectional, nationwide survey

Background: Myofascial pain is a common dysfunction with a lifetime prevalence affecting up to 85% of the general population. Current guidelines for the management of myofascial pain are not available. In this study we investigated how physicians on the basis of prescription behaviour evaluate the effectiveness of treatment options in their management of myofascial pain. Methods: We conducted a cross-sectional, nationwide survey with a standardized questionnaire among 332 physicians (79.8% male, 25.6% female, 47.5 +/- 9.6 years) experienced in treating patients with myofascial pain. Recruitment of physicians took place at three German meetings of pain therapists, rheumatologists and orthopaedists, respectively. Physicians estimated the prevalence of myofascial pain amongst patients in their practices, stated what treatments they used routinely and then rated the perceived treatment effectiveness on a six-point scale (with 1 being excellent). Data are expressed as mean +/- standard deviation. Results: The estimated overall prevalence of active myofascial trigger points is 46.1 +/- 27.4%. Frequently prescribed treatments are analgesics, mainly metamizol/paracetamol (91.6%), non-steroidal anti-inflammatory drugs/coxibs (87.0%) or weak opioids (81.8%), and physical therapies, mainly manual therapy (81.1%), TENS (72.9%) or acupuncture (60.2%). Overall effectiveness ratings for analgesics (2.9 +/- 0.7) and physical therapies were moderate (2.5 +/- 0.8). Effectiveness ratings of the various treatment options between specialities were widely variant. 54.3% of all physicians characterized the available treatment options as insufficient. Conclusions: Myofascial pain was estimated a prevalent condition. Despite a variety of commonly prescribed treatments, the moderate effectiveness ratings and the frequent characterizations of the available treatments as insufficient suggest an urgent need for clinical research to establish evidence-based guidelines for the treatment of myofascial pain syndrome

Effects of online marketplace-sourced over-the-counter tooth whitening products on the colour, microhardness, and surface topography of enamel: an in vitro study

Objectives: This study compared the whitening effect, microhardness, and enamel surface alterations of over-the-counter (OTC) tooth bleaching products with those of a dentist-prescribed at-home bleaching agent. Materials and methods: The products available on a popular online marketplace were comprehensively searched and then rated using a specific formula. The effects of the lowest-rated OTC agent (LRA) and the highest-rated OTC agent (HRA) were compared with those of a dentist-prescribed bleaching agent (DPA) on the enamel of extracted human teeth. The bleaching efficacy, post-bleaching microhardness changes, and morphological alterations were assessed by spectrophotometric analysis, Vickers hardness testing, and scanning electron microscopy (SEM) respectively. Statistical analyses included one-way ANOVA and post hoc tests, maintaining a significance level of P < 0.05. Results: The search of the online marketplace revealed 15 products. The LRA (Teeth Whitening Serum Gel, GEN, China) and the HRA (Bright White-Lovely Smile Premium Teeth Whitening strips, Ray of Smile, USA) were identified on the basis of their ranking. DPA resulted in significantly better tooth whitening than did LRA. The enamel microhardness was lower in the LRA treatment group (14.2%) than in the control and HRA treatment groups (8.84% and 7.26%, respectively). LRA also caused severe topographical alterations to the enamel. Conclusion: Compared with the poorly rated product, the dentist-prescribed tooth bleaching product resulted in greater colour improvement, less microhardness reduction, and surface changes. The highest-rated product was comparable with the dentist-prescribed agent in this study

The Pathophysiology of Inhalational Brucellosis in Balb/c Mice

To characterize the clinical presentation and pathophysiology of inhalational brucellosis, Balb/c mice were challenged with Brucella melitensis 16M in a nose-only aerosol exposure chamber. A low dose of 1000 cfu/animal of B. melitensis resulted in 45% of mice with tissue burdens eight weeks post-challenge. The natural history of brucellosis in mice challenged by higher aerosol doses was examined by serial euthanizing mice over an eight week period. Higher challenge doses of 1.00E+05 and 5.00E+05 cfu resulted in positive blood cultures 14 days post-challenge and bacterial burdens were observed in the lung, liver and/or spleens 14 days post-challenge. In addition, the progression of brucellosis was similar between mice challenged by the intranasal and aerosol routes. The results from this study support the use of the Balb/c aerosol nose-only brucellosis mouse model for the evaluation of therapeutics against inhalational brucellosis