Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance.

BackgroundSince pulmonary hypertension (PH) in patients with chronic obstructive pulmonary diseases (COPD) causes poor prognosis and inflammatory process involved in PH, it is supposed that Statins with anti-inflammatory effects might be useful in the treatment of PH.ObjectivesThe aim of this study was to evaluate the influence of Atorvastatin on the treatment of pulmonary hypertension in patients with COPD.Patients and MethodsA registered (IRCT201108257411N1), triple-blind, randomized controlled trial was performed in Rasoule Akram hospital, Tehran, from 2009 to 2011. Forty five patients with secondary pulmonary hypertension due to COPD were recruited and randomized to two groups receiving either Atorvastatin 40 mg/d or placebo in addition to their current treatment for 6 months. The outcomes including systolic pulmonary arterial hypertension (SPAH), cardiac output (CO), right ventricular size (RVS), CRP, 6 min walk distance test (6MWD), and spirometry parameters were measured after 6 months.ResultsBaseline characteristics were similar in both groups. After 6 months, pulmonary hypertension changed from 48.5 ± 6.9 to 42.9 ± 9.3 mmHg for Atorvastatin users and from 49.7 ± 11.4 to 48.2 ± 14.6 mmHg for Placebo users (P = 0.19, CI - 13.57 - 2.89), 6MWD after 6 months was 339 ± 155 meters in case group versus 340 ± 106 meters in control group (P = 0.98, CI - 92.58 - 91.15). There were no significant changes in other outcomes including CRP, RVS, CO and spirometry parameters.ConclusionsAlthough we found a trend towards decreasing SPAH and improving 6MWD, no statistically significant shift were detected in our outcomes due to inadequate sample size.

PurposeTo compare PubMed Clinical Queries and UpToDate regarding the amount and speed of information retrieval and users' satisfaction.MethodA cross-over randomized trial was conducted in February 2009 in Tehran University of Medical Sciences that included 44 year-one or two residents who participated in an information mastery workshop. A one-hour lecture on the principles of information mastery was organized followed by self learning slide shows before using each database. Subsequently, participants were randomly assigned to answer 2 clinical scenarios using either UpToDate or PubMed Clinical Queries then crossed to use the other database to answer 2 different clinical scenarios. The proportion of relevantly answered clinical scenarios, time to answer retrieval, and users' satisfaction were measured in each database.ResultsBased on intention-to-treat analysis, participants retrieved the answer of 67 (76%) questions using UpToDate and 38 (43%) questions using PubMed Clinical Queries (P<0.001). The median time to answer retrieval was 17 min (95% CI: 16 to 18) using UpToDate compared to 29 min (95% CI: 26 to 32) using PubMed Clinical Queries (P<0.001). The satisfaction with the accuracy of retrieved answers, interaction with UpToDate and also overall satisfaction were higher among UpToDate users compared to PubMed Clinical Queries users (P<0.001).ConclusionsFor first time users, using UpToDate compared to Pubmed Clinical Querries can lead to not only a higher proportion of relevant answer retrieval within a shorter time, but also a higher users' satisfaction. So, addition of tutoring pre-appraised sources such as UpToDate to the information mastery curricula seems to be highly efficient.

Cu supplementation during pregnancy could not influence positively on ROM; however, it could improve some mood status of the women.

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UpToDate seems more comprehensive in content and also faster than the other three evidence-based textbooks. Thus, it may be considered as one of the best sources for answering clinicians' questions at the point of care.

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