Menopausal hormone therapy and pancreatic cancer risk in women : a population-based matched cohort study

Background: The role of menopausal hormone therapy (MHT) in the development of pancreatic cancer is inconclusive owing to small studies and lack of proper study design. Methods: This population-based matched cohort study included all Swedish women who used systemic MHT between 1 July 2005 and 31 December 2012. For each user of MHT, three never-users of MHT were randomly selected, matched for childbirth, history of thromboembolic events, and previous hysterectomy, as well as for year of birth, diabetes, obesity, and smoking- or alcohol-related disorders. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MHT use and pancreatic cancer. The effect of MHT duration on pancreatic cancer development was calculated using multivariable Poisson regression. Results: There were 290,186 ever-users of MHT and 870,165 matched never-users. During the follow-up, 311 (0.0011%) ever-users of MHT and 1220 (0.0014) never-users developed pancreatic cancer. In a multivariable adjusted model, ever-users had a 23% reduced risk (OR 0.77; 95% CI: 0.68-0.87) of pancreatic cancer. This risk decreased by 35% (incidence rate ratio (IRR) 0.65; 95% CI: 0.33-1.27) in women who used MHT 1-2 years and by 60% (IRR 0.40; 95% CI: 0.18-0.88) in women who used MHT3 years compared to women with <1 year of MHT use. The type of MHT did not change the results. Conclusion: Systemic MHT use might reduce the risk of pancreatic cancer

Lower Blood Calcium Associates with Unfavorable Prognosis and Predicts for Bone Metastasis in NSCLC

Ionized calcium was involved in various cellular signal pathways,and regulates many cellular processes, including those relevant to tumorigenesis. We hypothesis that imbalance of calcium homeostasis is correlated with development of lung carcinomas. We collected the clinical data of 1084 patients with non small cell lung cancer (NSCLC) treated in Shandong Provincial Hospital, Shandong University. Logistic regression was used to determine the association between calcium levels and clinical characteristics, and COX regression and Kaplan-Meier model were applied to analyze risk factors on overall survival. Blood electrolytes were tested before treatment; and nearly 16% patients with NSCLC were complained with decreased blood calcium, which is more frequent than that in other electrolytes. Further, Multivariate logistic regression analysis disclosed that there were significant correlation between blood calcium decrease and moderate and poor differentiation (P = 0.012, OR = 1.926 (1.203–4.219)), squamous cell carcinoma (P = 0.024, OR = 1.968(1.094–3.540)), and bone metastasis (P = 0.032, OR = 0.396(0.235–0.669)). In multivariate COX regression analysis, advanced lymph node stage and decreased blood calcium were significantly and independent, unfavorable prognostic factors (P<0.001). Finally, the Kaplan-Meier Survival curve revealed that blood calcium decrease was associated with shorter survival (Log-rank; χ2 = 26.172,P<0.001). Our finding indicates that lower blood calcium levels are associated with a higher risk of unfavorable prognosis and bone metastasis of NSCLC

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease

Balance in single-limb stance in healthy subjects – reliability of testing procedure and the effect of short-duration sub-maximal cycling

BACKGROUND: To assess balance in single-limb stance, center of pressure movements can be registered by stabilometry with force platforms. This can be used for evaluation of injuries to the lower extremities. It is important to ensure that the assessment tools we use in the clinical setting and in research have minimal measurement error. Previous studies have shown that the ability to maintain standing balance is decreased by fatiguing exercise. There is, however, a need for further studies regarding possible effects of general exercise on balance in single-limb stance. The aims of this study were: 1) to assess the test-retest reliability of balance variables measured in single-limb stance on a force platform, and 2) to study the effect of exercise on balance in single-limb stance, in healthy subjects. METHODS: Forty-two individuals were examined for test-retest reliability, and 24 individuals were tested before (pre-exercise) and after (post-exercise) short-duration, sub-maximal cycling. Amplitude and average speed of center of pressure movements were registered in the frontal and sagittal planes. Mean difference between test and retest with 95% confidence interval, the intraclass correlation coefficient, and the Bland and Altman graphs with limits of agreement, were used as statistical methods for assessing test-retest reliability. The paired t-test was used for comparisons between pre- and post-exercise measurements. RESULTS: No difference was found between test and retest. The intraclass correlation coefficients ranged from 0.79 to 0.95 in all stabilometric variables except one. The limits of agreement revealed that small changes in an individual's performance cannot be detected. Higher values were found after cycling in three of the eight stabilometric variables. CONCLUSIONS: The absence of systematic variation and the high ICC values, indicate that the test is reliable for distinguishing among groups of subjects. However, relatively large differences in an individual's balance performance would be required to confidently state that a change is real. The higher values found after cycling, indicate compensatory mechanisms intended to maintain balance, or a decreased ability to maintain balance. It is recommended that average speed and DEV 10; the variables showing the best reliability and effects of exercise, be used in future studies

Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer

Ionized calcium (Ca) and magnesium (Mg) compete as essential messengers to regulate cell proliferation and inflammation. We hypothesized that inadequate Mg levels, perhaps relative to Ca levels (e.g. a high Ca/Mg ratio) are associated with greater prostate cancer risk.In this biomarker sub-study of the Nashville Men's Health Study (NMHS), we included 494 NMHS participants, consisting of 98 high-grade (Gleason≥7) and 100 low-grade cancer cases, 133 prostate intraepithelial neoplasia (PIN) cases, and 163 controls without cancer or PIN at biopsy. Linear and logistic regression were used to determine associations between blood Ca, Mg, and the Ca/Mg ratio across controls and case groups while adjusting for potential confounding factors.Serum Mg levels were significantly lower, while the Ca/Mg ratio was significantly higher, among high-grade cases vs. controls (p = 0.04, p = 0.01, respectively). Elevated Mg was significantly associated with a lower risk of high-grade prostate cancer (OR = 0.26 (0.09, 0.85)). An elevated Ca/Mg ratio was also associated with an increased risk of high-grade prostate cancer (OR = 2.81 (1.24, 6.36) adjusted for serum Ca and Mg). In contrast, blood Ca levels were not significantly associated with prostate cancer or PIN.Mg, Ca, or Ca/Mg levels were not associated with low-grade cancer, PIN, PSA levels, prostate volume, or BPH treatment.Low blood Mg levels and a high Ca/Mg ratio were significantly associated with high-grade prostate cancer. These findings suggest Mg affects prostate cancer risk perhaps through interacting with Ca

Polyglutamine Expansion Accelerates the Dynamics of Ataxin-1 and Does Not Result in Aggregate Formation

Polyglutamine expansion disorders are caused by an expansion of the polyglutamine (polyQ) tract in the disease related protein, leading to severe neurodegeneration. All polyQ disorders are hallmarked by the presence of intracellular aggregates containing the expanded protein in affected neurons. The polyQ disorder SpinoCerebellar Ataxia 1 (SCA1) is caused by a polyQ-expansion in the ataxin-1 protein, which is thought to lead to nuclear aggregates.Using advanced live cell fluorescence microscopy and a filter retardation assay we show that nuclear accumulations formed by polyQ-expanded ataxin-1 do not resemble aggregates of other polyQ-expanded proteins. Instead of being static, insoluble aggregates, nuclear accumulations formed by the polyQ-expanded ataxin-1 showed enhanced intracellular kinetics as compared to wild-type ataxin-1. During mitosis, ataxin-1 accumulations redistributed equally among daughter cells, in contrast to polyQ aggregates. Interestingly, polyQ expansion did not affect the nuclear-cytoplasmic shuttling of ataxin-1 as proposed before.These results indicate that polyQ expansion does not necessarily lead to aggregate formation, and that the enhanced kinetics may affect the nuclear function of ataxin-1. The unexpected findings for a polyQ-expanded protein and their consequences for ongoing SCA1 research are discussed

Pre-Diagnostic Plasma 25-Hydroxyvitamin D Levels and Risk of Non-Melanoma Skin Cancer in Women

Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses' Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52-2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile = 3.77, 95% CI = 1.70-8.36, P for trend= 0.0002).In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer