Annual variation in the levels of transcripts of sex-specific genes in the mantle of the common mussel, Mytilus edulis

Mytilus species are used as sentinels for the assessment of environmental health but sex or stage in the reproduction cycle is rarely considered even though both parameters are likely to influence responses to pollution. We have validated the use of a qPCR assay for sex identification and related the levels of transcripts to the reproductive cycle. A temporal study of mantle of Mytilus edulis found transcripts of male-specific vitelline coat lysin (VCL) and female-specific vitelline envelope receptor for lysin (VERL) could identify sex over a complete year. The levels of VCL/VERL were proportional to the numbers of sperm/ova and are indicative of the stage of the reproductive cycle. Maximal levels of VCL and VERL were found in February 2009 declining to minima between July - August before increasing and re-attaining a peak in February 2010. Water temperature may influence these transitions since they coincide with minimal water temperature in February and maximal temperature in August. An identical pattern of variation was found for a cryptic female-specific transcript (H5) but a very different pattern was observed for oestrogen receptor 2 (ER2). ER2 varied in a sex-specific way with male > female for most of the cycle, with a female maxima in July and a male maxima in December. Using artificially spawned animals, the transcripts for VCL, VERL and H5 were shown to be present in gametes and thus their disappearance from mantle is indicative of spawning. VCL and VERL are present at equivalent levels in February and July-August but during gametogenesis (August to January) and spawning (March to June) VCL is present at lower relative amounts than VERL. This may indicate sex-specific control mechanisms for these processes and highlight a potential pressure point leading to reduced reproductive output if environmental factors cause asynchrony to gamete maturation or release

Rural factors and survival from cancer: analysis of Scottish cancer registrations

In this survival study 63 976 patients diagnosed with one of six common cancers in Scotland were followed up. Increasing distance from a cancer centre was associated with less chance of diagnosis before death for stomach, breast and colorectal cancers and poorer survival after diagnosis for prostate and lung cancers. © 2000 Cancer Research Campaig

Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review

The published literature comparing surgery, with or without adjuvant endocrine therapy, with endocrine therapy alone in older women with operable breast cancer was systematically reviewed.The design used is Cochrane review. Randomised controlled trials retrieved from the Cochrane Breast Cancer Group Specialised Register on 29 June 2005. Eligible studies recruited women aged 70 years or over with operable breast cancer, fit for surgery under general anaesthia. The studies compared surgery (either mastectomy or wide local excision, with or without endocrine therapy) to endocrine therapy alone. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Double data extraction and quality assessment were undertaken. Seven eligible trials were identified of which six had published time-to-event data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. When surgery alone was compared to endocrine therapy alone, there was no significant difference in OS (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.74–1.30, P=0.9), but a significant difference in PFS (HR 0.55, 95% CI 0.39–0.77, P=0.0006). When surgery with adjuvant endocrine therapy was compared to endocrine therapy alone, there was no significant difference in OS (HR 0.86, 95% CI 0.73–1.00, P=0.06), but a significant difference in PFS (HR 0.65 (95% CI 0.53–0.81, P=0.0001) for surgery plus endocrine therapy vs primary endocrine. The regimens have different side effect profiles with one study suggesting increased psychosocial morbidity at 3 months in the surgical arm, which resolves by 2 years. Primary endocrine therapy with tamoxifen is associated with inferior local disease control but non-inferior survival to surgery for breast cancer in older women. Trials are needed to evaluate appropriate selection criteria for its use in terms of patient co-morbidity and quality of life. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for this population

Indicators of breast cancer severity and appropriateness of surgery based on hospital administrative data in the Lazio Region, Italy

BACKGROUND: Administrative data can serve as an easily available source for epidemiological and evaluation studies. The aim of this study is to evaluate the use of hospital administrative data to determine breast cancer severity and the appropriateness of surgical treatment. METHODS: the study population consisted of 398 patients randomly selected from a cohort of women hospitalized for first-time breast cancer surgery in the Lazio Region, Italy. Tumor severity was defined in three different ways: 1) tumor size; 2) clinical stage (TNM); 3) severity indicator based on HIS data (SI). Sensitivity, specificity, and positive predictive value (PPV) of the severity indicator in evaluating appropriateness of surgery were calculated. The accuracy of HIS data was measured using Kappa statistic. RESULTS: Most of 387 cases were classified as T1 and T2 (tumor size), more than 70% were in stage I or II and the SI classified 60% of cases in medium-low category. Variation from guidelines indications identified under and over treatments. The accuracy of the SI to predict under-treatment was relatively good (58% of all procedures classified as under-treatment using pT where also classified as such using SI), and even greater predicting over-treatment (88.2% of all procedures classified as over treatment using pT where also classified as such using SI). Agreement between clinical chart and hospital discharge reports was K = 0.35. CONCLUSION: Our findings suggest that administrative data need to be used with caution when evaluating surgical appropriateness, mainly because of the limited ability of SI to predict tumor size and the questionable quality of HIS data as observed in other studies

HDAC6 Regulates LPS-Tolerance in Astrocytes

Inflammatory tolerance is a crucial mechanism that limits inflammatory responses in order to avoid prolonged inflammation that may damage the host. Evidence that chronic inflammation contributes to the neuropathology of prevalent neurodegenerative and psychiatric diseases suggests that inflammatory tolerance mechanisms are often inadequate to control detrimental inflammation in the central nervous system. Thus, identifying mechanisms that regulate neuroinflammatory tolerance may reveal opportunities for bolstering tolerance to reduce chronic inflammation in these diseases. Examination of tolerance after repeated lipopolysaccharide (LPS) treatment of mouse primary astrocytes demonstrated that histone deacetylase (HDAC) activity promoted tolerance, opposite to the action of glycogen synthase kinase-3 (GSK3), which counteracts tolerance. HDAC6 in particular was found to be critical for tolerance induction, as its deacetylation of acetyl-tubulin was increased during LPS tolerance, this was enhanced by inhibition of GSK3, and the HDAC6 inhibitor tubacin completely blocked tolerance and the promotion of tolerance by inhibition of GSK3. These results reveal opposing interactions between HDAC6 and GSK3 in regulating tolerance, and indicate that shifting the balance between these two opposing forces on inflammatory tolerance can obliterate or enhance tolerance to LPS in astrocytes

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Assaying Total Carotenoids in Flours of Corn and Sweetpotato by Laser Photoacoustic Spectroscopy

This study describes the application of the laser photoacoustic spectroscopy (PAS) for quantification of total carotenoids (TC) in corn flours and sweetpotato flours. Overall, thirty-three different corn flours and nine sweetpotato flours were investigated. All PAS measurements were performed at room temperature using 488-nm argon laser radiation for excitation and mechanical modulation of 9 and 30 Hz. The measurements were repeated within a run and within several days or months. The UV–Vis spectrophotometry was used as the reference method. The concentration range that allows for the reliable analysis of TC spans a region from 1 to 40 mg kg−1 for corn flours and from 9 to 40 mg kg−1 for sweetpotato flours. In the case of sweetpotato flours, the quantification may extend even to 240 mg kg−1 TC. The estimated detection limit values for TC in corn and sweetpotato flours were 0.1 and 0.3 mg kg−1, respectively. The computed repeatability (n = 3–12) and intermediate precision (n = 6–28) RSD values at 9 and 30 Hz are comparable: 0.1–17.1% and 5.3–14.7% for corn flours as compared with 1.4–9.1% and 4.2–23.0% for sweetpotato flours. Our results show that PAS can be successfully used as a new analytical tool to simply and rapidly screen the flours for their nutritional potential based on the total carotenoid concentration

γ-Tocotrienol suppresses prostate cancer cell proliferation and invasion through multiple-signalling pathways

Tocotrienol-rich fraction (TRF) has demonstrated antiproliferative effect on prostate cancer (PCa) cells. To elucidate this anticancer property in PCa cells, this study aimed, first, to identify the most potent isomer for eliminating PCa cells; and second, to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of γ-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of pro-caspases and the presence of sub-G1 cell population. Examination of the pro-survival genes revealed that the γ-tocotrienol-induced cell death was associated with suppression of NF-κB, EGF-R and Id family proteins (Id1 and Id3). Meanwhile, γ-tocotrienol treatment also resulted in the induction of JNK-signalling pathway and inhibition of JNK activity by a specific inhibitor (SP600125) was able to partially block the effect of γ-tocotrienol. Interestingly, γ-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and γ-catenin expression, which was associated with suppression of cell invasion capability. Furthermore, a synergistic effect was observed when cells were co-treated with γ-tocotrienol and Docetaxel. Our results suggested that the antiproliferative effect of γ-tocotrienol act through multiple-signalling pathways, and demonstrated for the first time the anti-invasion and chemosensitisation effect of γ-tocotrienol against PCa cells