Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.</p> <p>Methods/Design</p> <p>The EVIDIMS trial is a German multi-center, stratified, randomized, controlled and double-blind clinical phase II pilot study. Eighty patients with the diagnosis of definite multiple sclerosis or clinically isolated syndrome who are on a stable immunomodulatory treatment with interferon-β1b will be randomized to additionally receive either high-dose (average daily dose 10.200 IU) or low-dose (average daily dose 200 IU) cholecalciferol for a total period of 18 months. The primary outcome measure is the number of new lesions detected on T2-weighted cranial MRI at 3 tesla. Secondary endpoints include additional magnetic resonance imaging and optical coherence tomography parameters for neuroinflammation and -degeneration, clinical parameters for disease activity, as well as cognition, fatigue, depression, and quality of life. Safety and tolerability of high-dose vitamin D supplementation are further outcome parameters.</p> <p>Discussion</p> <p>In light of the discrepancy between existing epidemiological and preclinical data on the one hand and available clinical data on the other the EVIDIMS trial will substantially contribute to the evaluation of the efficacy of high-dose vitamin D supplementation in MS patients. The study design presented here fulfills the criteria of a high-quality clinical phase II trial in MS.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01440062">NCT01440062</a></p

Trends of increase in western medical services in traditional medicine hospitals in china

Background: Compare changes in types of hospital service revenues between traditional Chinese medicine (TCM) hospitals and Western-medicine based general hospitals. Methods: 97 TCM hospitals and 103 general hospitals were surveyed in years of 2000 and 2004. Six types of medical service revenue between the two types of hospitals were compared overtime. The national statistics from 1999 to 2008 were also used as complementary evidence. Results: For TCM hospitals, the percentage of service revenue from Western medicine increased from 44.3% to 47.4% while the percentage of service revenue from TCM declined from 26.4% to 18.8% from 1999 to 2004. Percentages of revenue from laboratory tests and surgical procedures for both types of hospitals increased and the discrepancy between the two types of hospitals was narrowed from 1999 to 2004. For TCM hospitals, revenues from laboratory tests increased from 3.64% to 5.06% and revenues from surgical procedures increased from 3.44% to 7.02%. General hospitals\u27 TCM drug revenue in outpatient care declined insignificantly from 5.26% to 3.87%, while the decline for the TCM hospitals was significant from 19.73% to 13.77%. The national statistics from 1999 to 2008 showed similar trends that the percentage of revenue from Western medicine for TCM hospitals increased from 59.6% in 1999 to 62.2% in 2003 and 66.1% in 2008 while the percentage of revenue from TCM for TCM hospitals decreased from 18.0% in 1999, 15.4% in 2003, and 13.7% in 2008. Conclusion: Western medicine has become a vital revenue source for TCM hospitals in the current Chinese health care environment where government subsidies to health care facilities have significantly declined. Policies need to encourage TCM hospitals to identify their own special and effective services, improve public perception, increase demand, strengthen financial sources, and ultimately make contributions to preserving one of the national treasures

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

RNAi-mediated silencing of the Bmi-1 gene causes growth inhibition and enhances doxorubicin-induced apoptosis in MCF-7 cells

The oncogene Bmi-1 is a member of the Polycomb group gene family. Its expression is found to be greatly increased in a number of malignant tumors including breast cancer. This could suggest Bmi-1 as a potent therapeutic target. In this study, RNAi was introduced to down-regulate the expression of Bmi-1 in a highly malignant breast adenocarcinoma cell line, MCF-7. A thorough study of the biological behavior and chemosensitivity changes of the MCF-7 cells was carried out in context to the therapeutic potential of Bmi-1. The results obtained indicated that siRNA targeting of Bmi-1 could lead to an efficient and specific inhibition of endogenous Bmi-1 activity. The mRNA and protein expression of Bmi-1 were determined by RT-PCR and Western blot, respectively. Furthermore, silencing of Bmi-1 resulted in a drastic inhibition of the growth of MCF-7 cells as well as G1 /S phase transition. The number of target cells was found to increase in phase G 0 /G 1 and decrease in the S phase, but no increase in the basal level of apoptosis was noticed. On the other hand, a reduction in the expression of cyclin D1 and an increase in the expression of p21 were also noticed. Silencing of Bmi-1 made the MCF-7 cells more sensitive to the chemotherapeutic agent doxorubicin and induced a significantly higher percentage of apoptotic cells. Here, we report on a study regarding the RNAi-mediated silencing of the Bmi-1 gene in breast cancer

Using an oblique incident laser beam to measure the optical properties of stomach mucosa/submucosa tissue

<p>Abstract</p> <p>Background</p> <p>The purpose of the study is to determine the optical properties and their differences for normal human stomach mucosa/submucosa tissue in the cardiac orifice <it>in vitro </it>at 635, 730, 808, 890 and 980 nm wavelengths of laser.</p> <p>Methods</p> <p>The measurements were performed using a CCD detector, and the optical properties were assessed from the measurements using the spatially resolved reflectance, and nonlinear fitting of diffusion equation.</p> <p>Results</p> <p>The results of measurement showed that the absorption coefficients, the reduced scattering coefficients, the optical penetration depths, the diffusion coefficients, the diffuse reflectance and the shifts of diffuse reflectance of tissue samples at five different wavelengths vary with a change of wavelength. The maximum absorption coefficient for tissue samples is 0.265 mm^-1at 980 nm, and the minimum absorption coefficient is 0.0332 mm^-1at 730 nm, and the maximum difference in the absorption coefficients is 698% between 730 and 980 nm, and the minimum difference is 1.61% between 635 and 808 nm. The maximum reduced scattering coefficient for tissue samples is 1.19 mm^-1at 635 nm, and the minimum reduced scattering coefficient is 0.521 mm^-1at 980 nm, and the maximum difference in the reduced scattering coefficients is 128% between 635 and 980 nm, and the minimum difference is 1.15% between 890 and 980 nm. The maximum optical penetration depth for tissue samples is 3.57 mm at 808 nm, and the minimum optical penetration depth is 1.43 mm at 980 nm. The maximum diffusion constant for tissue samples is 0.608 mm at 890 nm, and the minimum diffusion constant is 0.278 mm at 635 nm. The maximum diffuse reflectance is 3.57 mm^-1at 808 nm, and the minimum diffuse reflectance is 1.43 mm^-1at 980 nm. The maximum shift Δx of diffuse reflectance is 1.11 mm^-1at 890 nm, and the minimum shift Δx of diffuse reflectance is 0.507 mm^-1at 635 nm.</p> <p>Conclusion</p> <p>The absorption coefficients, the reduced scattering coefficients, the optical penetration depths, the diffusion coefficients, the diffuse reflectance and the shifts of diffuse reflectance of tissue samples at 635, 730, 808, 890 and 980 nm wavelengths vary with a change of wavelength. There were significant differences in the optical properties for tissue samples at five different wavelengths (<it>P </it>< 0.01).</p

Multi-susceptibility genes associated with the risk of the development stages of esophageal squamous cell cancer in Feicheng County

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk.</p> <p>Methods</p> <p>A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for <it>CYP2E1 </it>G1259C, <it>hOGG1 </it>C326G, <it>MTHFR </it>C677T, <it>MPO </it>G463A, and <it>ALDH2 </it>allele genes were identified in blood samples collected from all participants.</p> <p>Results</p> <p>The alleles <it>ALDH2 </it>and <it>MTHFR </it>C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the <it>ALDH </it>1*1 genotype, the <it>ALDH </it>2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of <it>MTHFR </it>C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of <it>ALDH </it>2 and TT/TC of <it>MTHFR </it>C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (OR_G) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus.</p> <p>Conclusions</p> <p>The study demonstrated that the genotypes <it>ALDH2*2 </it>and <it>MTHFR </it>677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.</p

Opportunities, challenges and systems requirements for developing post-abortion family planning services: Perceptions of service stakeholders in China

Post-abortion family planning (PAFP) has been proposed as a key strategy to decrease unintended pregnancy and repeat induced abortions. However, the accessibility and quality of PAFP services remain a challenge in many countries including China where more than 10 million unintended pregnancies occur each year. Most of these unwanted pregnancies end in repeated induced abortions. This paper aims to explore service providers’ perceptions of the current situation regarding family planning and abortion service needs, provision, utilization, and the feasibility and acceptability of high quality PAFP in the future. Qualitative methods, including in-depth interviews and focus group discussions, were used with family planning policy makers, health managers, and service providers. Three provinces—Zhejiang, Hubei and Yunnan—were purposively selected, representing high, medium and relatively undeveloped areas of China. A total of fifty-three in-depth interviews and ten focus-group discussions were conducted and analysed thematically. Increased numbers of abortions among young, unmarried women were perceived as a major reason for high numbers of abortions. Participants attributed this to increasing socio-cultural acceptability of premarital sex, and simultaneously, lack of understanding or awareness of contraception among young people. The majority of service stakeholders acknowledged that free family planning services were neither targeted at, nor accessible to unmarried people. The extent of PAFP provision is variable and limited. However, service providers expressed willingness and enthusiasm towards providing PAFP services in the future. Three main considerations were expressed regarding the feasibility of developing and implementing PAFP services: policy support, human resources, and financial resources. The study indicated that key service stakeholders show demand for and perceive considerable opportunities to develop PAFP in China. However, changes are needed to enable the systematic development of high quality PAFP, including actively targeting young and unmarried people in service provision, obtaining policy support and increasing the investment of human and financial resources

Political and social determinants of life expectancy in less developed countries: a longitudinal study

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine the longitudinal contributions of four political and socioeconomic factors to the increase in life expectancy in less developed countries (LDCs) between 1970 and 2004.</p> <p>Methods</p> <p>We collected 35 years of annual data for 119 LDCs on life expectancy at birth and on four key socioeconomic indicators: economy, measured by log10 gross domestic product per capita at purchasing power parity; educational environment, measured by the literacy rate of the adult population aged 15 years and over; nutritional status, measured by the proportion of undernourished people in the population; and political regime, measured by the regime score from the Polity IV database. Using linear mixed models, we analyzed the longitudinal effects of these multiple factors on life expectancy at birth with a lag of 0-10 years, adjusting for both time and regional correlations.</p> <p>Results</p> <p>The LDCs' increases in life expectancy over time were associated with all four factors. Political regime had the least influence on increased life expectancy to begin with, but became significant starting in the 3rd year and continued to increase, while the impact of the other socioeconomic factors began strong but continually decreased over time. The combined effects of these four socioeconomic and political determinants contributed 54.74% - 98.16% of the life expectancy gains throughout the lag periods of 0-10 years.</p> <p>Conclusions</p> <p>Though the effect of democratic politics on increasing life expectancy was relatively small in the short term when compared to the effects of the other socioeconomic factors, the long-term impact of democracy should not be underestimated.</p

Hyperglycemic Myocardial Damage Is Mediated by Proinflammatory Cytokine: Macrophage Migration Inhibitory Factor

Diabetes has been regarded as an inflammatory condition which is associated with left ventricular diastolic dysfunction (LVDD). The purpose of this study was to examine the expression levels of macrophage migration inhibitory factor (MIF) and G protein-coupled receptor kinase 2 (GRK2) in patients with early diabetic cardiomyopathy, and to investigate the mechanisms involved in MIF expression and GRK2 activation.83 patients in the age range of 30-64 years with type 2 diabetes and 30 matched healthy men were recruited. Left ventricular diastolic function was evaluated by cardiac Doppler echocardiography. Plasma MIF levels were determined by ELISA. To confirm the clinical observation, we also studied MIF expression in prediabetic rats with impaired glucose tolerance (IGT) and relationship between MIF and GRK2 expression in H9C2 cardiomyoblasts exposed to high glucose.Compared with healthy subjects, patients with diabetes have significantly increased levels of plasma MIF which was further increased in diabetic patients with Left ventricular diastolic dysfunction (LVDD). The increased plasma MIF levels in diabetic patients correlated with plasma glucose, glycosylated hemoglobin and urine albumin levels. We observed a significant number of TUNEL-positive cells in the myocardium of IGT-rats but not in the control rats. Moreover, we found higher MIF expression in the heart of IGT with cardiac dysfunction compared to that of the controls. In H9C2 cardiomyoblast cells, MIF and GRK2 expression was significantly increased in a glucose concentration-dependant manner. Furthermore, GRK2 expression was abolished by siRNA knockdown of MIF and by the inhibition of CXCR4 in H9C2 cells.Our findings indicate that hyperglycemia is a causal factor for increased levels of pro-inflammatory cytokine MIF which plays a role in the development of cardiomyopathy occurring in patients with type 2 diabetes. The elevated levels of MIF are associated with cardiac dysfunction in diabetic patients, and the MIF effects are mediated by GRK2