Long-Term Quality of Life Improvement in Subjects with Healed Erosive Esophagitis: Treatment with Lansoprazole

Gastroesophageal reflux disease (GERD) is a chronic symptomatic condition and may be associated with erosive esophagitis (EE). Considerable data on the long-term maintenance of healing of EE are available, but data on long-term GERD symptom prevention and patient quality of life (QOL) are limited. To investigate QOL in subjects with healed EE who received 12 months of double-blind maintenance treatment with lansoprazole or ranitidine, followed by long-term open-label lansoprazole therapy to prevent recurrence of EE. Subjects with healed EE received 12 months of double-blind maintenance treatment with lansoprazole 15 mg once daily or ranitidine 150 mg twice daily, followed by dose-titrated, open-label lansoprazole therapy for up to 82 months. During double-blind treatment (n = 206), lansoprazole-treated patients showed significantly (P ≤ 0.05) greater improvements than ranitidine-treated patients in the frequency, severity, and ‘bothersomeness’ of heartburn, the symptom index, problems of activity limitation, eating and drinking problems, symptom problems, health distress, and social functioning. During dose-titrated, open-label treatment (n = 195), all disease-specific QOL scales except sleep improved significantly (P < 0.001) from open-label baseline at each time-point. Maintenance treatment with lansoprazole for 12 months in healed EE subjects produced significantly greater improvements in QOL indicators than ranitidine. These improvements were sustained during dose-titrated, open-label lansoprazole treatment

Cognitive behavioral therapy for depression among adults in Japanese clinical settings: a single-group study

<p>Abstract</p> <p>Background</p> <p>Empirical support for cognitive behavioral therapy (CBT) for treating Japanese patients with major depression is lacking, therefore, a feasibility study of CBT for depression in Japanese clinical settings is urgently required.</p> <p>Findings</p> <p>A culturally adapted, 16-week manualized individual CBT program for Japanese patients with major depressive disorder was developed. A total of 27 patients with major depression were enrolled in a single-group study with the purpose of testing the feasibility of the program. Twenty six patients (96%) completed the study. The mean total score on the Beck Depression Inventory-II (BDI-II) for all patients (Intention-to-treat sample) improved from 32.6 to 11.7, with a mean change of 20.8 (95% confidence interval: 17.0 to 24.8). Within-group effect size at the endpoint assessment was 2.64 (Cohen's d). Twenty-one patients (77.7%) showed treatment response and 17 patients (63.0%) achieved remission at the end of the program. Significant improvement was observed in measurement of subjective and objective depression severity (assessed by BDI-II, Quick Inventory of Depressive Symptomatology-Self Rated, and Hamilton Depression Rating Scale), dysfunctional attitude (assessed by Dysfunctional Attitude Scale), global functioning (assessed by Global Assessment of Functioning of DSM-IV) and subjective well-being (assessed by WHO Subjective Well-being Inventory) (all p values < 0.001).</p> <p>Conclusions</p> <p>Our manualized treatment comprised of a 16-week individual CBT program for major depression appears feasible and may achieve favorable treatment outcomes among Japanese patients with major depression. Further research involving a larger sample in a randomized, controlled trial design is warranted.</p> <p>Trial registration</p> <p>UMIN-CTR UMIN000002542.</p

Integrated Epigenome Profiling of Repressive Histone Modifications, DNA Methylation and Gene Expression in Normal and Malignant Urothelial Cells

Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with low and high-grade differentiation. We hypothesized that epigenetic gene regulation reflects an interaction between histone and DNA modifications, and differences between normal and malignant urothelial cells represent carcinogenic events within bladder cancer. To test this we profiled two repressive histone modifications (H3K9m3 and H3K27m3) using ChIP-Seq, cytosine methylation using MeDIP and mRNA expression in normal and malignant urothelial cell lines. In genes with low expression we identified H3K27m3 and DNA methylation each in 20–30% of genes and both marks in 5% of genes. H3K9m3 was detected in 5–10% of genes but was not associated with overall expression. DNA methylation was more closely related to gene expression in malignant than normal cells. H3K27m3 was the epigenetic mark most specifically correlated to gene silencing. Our data suggest that urothelial carcinogenesis is accompanied by a loss of control of both DNA methylation and H3k27 methylation. From our observations we identified a panel of genes with cancer specific-epigenetic mediated aberrant expression including those with reported carcinogenic functions and members potentially mediating a positive epigenetic feedback loop. Pathway enrichment analysis revealed genes marked by H3K9m3 were involved with cell homeostasis, those marked by H3K27m3 mediated pro-carcinogenic processes and those marked with cytosine methylation were mixed in function. In 150 normal and malignant urothelial samples, our gene panel correctly estimated expression in 65% of its members. Hierarchical clustering revealed that this gene panel stratified samples according to the presence and phenotype of bladder cancer

Preterm Birth in Caucasians Is Associated with Coagulation and Inflammation Pathway Gene Variants

Spontaneous preterm birth (<37 weeks gestation—PTB) occurs in ∼12% of pregnancies in the United States, and is the largest contributor to neonatal morbidity and mortality. PTB is a complex disease, potentially induced by several etiologic factors from multiple pathophysiologic pathways. To dissect the genetic risk factors of PTB a large-scale high-throughput candidate gene association study was performed examining 1536 SNP in 130 candidate genes from hypothesized PTB pathways. Maternal and fetal DNA from 370 US Caucasian birth-events (172 cases and 198 controls) was examined. Single locus, haplotype, and multi-locus association analyses were performed separately on maternal and fetal data. For maternal data the strongest associations were found in genes in the complement-coagulation pathway related to decidual hemorrhage in PTB. In this pathway 3 of 6 genes examined had SNPs significantly associated with PTB. These include factor V (FV) that was previously associated with PTB, factor VII (FVII), and tissue plasminogen activator (tPA). The single strongest effect was observed in tPA marker rs879293 with a significant allelic (p = 2.30×10−3) and genotypic association (p = 2.0×10−6) with PTB. The odds ratio (OR) for this SNP was 2.80 [CI 1.77–4.44] for a recessive model. Given that 6 of 8 markers in tPA were statistically significant, sliding window haplotype analyses were performed and revealed an associating 4 marker haplotype in tPA (p = 6.00×10−3). The single strongest effect in fetal DNA was observed in the inflammatory pathway at rs17121510 in the interleukin-10 receptor antagonist (IL-10RA) gene for allele (p = 0.01) and genotype (p = 3.34×10−4). The OR for the IL-10RA genotypic additive model was 1.92 [CI 1.15–3.19] (p = 2.00×10−3). Finally, exploratory multi-locus analyses in the complement and coagulation pathway were performed and revealed a potentially significant interaction between a marker in FV (rs2187952) and FVII (rs3211719) (p<0.001). These results support a role for genes in both the coagulation and inflammation pathways, and potentially different maternal and fetal genetic risks for PTB

Evaluation of metabolic syndrome in adults of Talca city, Chile

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Program for expectant and new mothers: a population-based study of participation

<p>Abstract</p> <p>Background</p> <p>The Manitoba Healthy Baby Program is aimed at promoting pre- and perinatal health and includes two components: 1) prenatal income supplement; 2) community support programs. The goal of this research was to determine the uptake of these components by target groups.</p> <p>Methods</p> <p>Data on participation in each of the two program components were linked to data on all hospital births in Manitoba between 2004/05 through 2007/08. Descriptive analyses of participation by maternal characteristics were produced. Logistic regression analyses were conducted to identify factors associated with participation in the two programs. Separate regressions were run for two groups of women giving birth during the study period: 1) total population; 2) those receiving provincial income assistance during the prenatal period.</p> <p>Results</p> <p>Almost 30% of women giving birth in Manitoba received the Healthy Baby prenatal income supplement, whereas only 12.6% participated in any community support programs. Over one quarter (26.4%) of pregnant women on income assistance did not apply for and receive the prenatal income supplement, despite all being eligible for it. Furthermore, 77.8% of women on income assistance did not participate in community support programs. Factors associated with both receipt of the prenatal benefit and participation in community support programs included lower SES, receipt of income assistance, obtaining adequate prenatal care, having completed high school and having depressive symptoms. Having more previous births was associated with higher odds of receiving the prenatal benefit, but lower odds of attending community support programs. Being married was associated with lower odds of receiving the prenatal benefit but higher odds of participating in community support programs.</p> <p>Conclusions</p> <p>Although uptake of the Healthy Baby program in Manitoba is greater for women in groups at risk for poorer perinatal outcomes, a substantial number of women eligible for this program are not receiving it; efforts to reach these women should be enhanced.</p

Fungal chitinases: diversity, mechanistic properties and biotechnological potential

Chitin derivatives, chitosan and substituted chito-oligosaccharides have a wide spectrum of applications ranging from medicine to cosmetics and dietary supplements. With advancing knowledge about the substrate-binding properties of chitinases, enzyme-based production of these biotechnologically relevant sugars from biological resources is becoming increasingly interesting. Fungi have high numbers of glycoside hydrolase family 18 chitinases with different substrate-binding site architectures. As presented in this review, the large diversity of fungal chitinases is an interesting starting point for protein engineering. In this review, recent data about the architecture of the substrate-binding clefts of fungal chitinases, in connection with their hydrolytic and transglycolytic abilities, and the development of chitinase inhibitors are summarized. Furthermore, the biological functions of chitinases, chitin and chitosan utilization by fungi, and the effects of these aspects on biotechnological applications, including protein overexpression and autolysis during industrial processes, are discussed in this review