Epigenetic Markers of Prostate Cancer in Plasma Circulating DNA.

Epigenetic markers of prostate cancer in plasma circulating DNA.

Filed under: Addiction Rehab

Hum Mol Genet. 2012 May 22;
Cortese R, Kwan A, Lalonde E, Bryzgunova O, Bondar A, Wu Y, Gordevicius J, Park M, Oh G, Kaminsky Z, Tverkuviene J, Laurinavicius A, Jankevicius F, Sendorek DH, Haider S, Wang SC, Jarmalaite S, Laktionov P, Boutros PC, Petronis A

Epigenetic differences are a common feature of many diseases, including cancer, and disease-associated changes have even been detected in bodily fluids. DNA modification studies in circulating DNA (cirDNA) may lead to the development of specific non-invasive biomarkers. To test this hypothesis, we investigated cirDNA modifications in prostate cancer patients with locally-confined disease (n = 19), in patients with benign prostate hyperplasias (n = 20), and in men without any known prostate disease (n = 20). This initial discovery screen identified 39 disease-associated changes in cirDNA modification, and seven of these were validated using sodium bisulfite-based mapping of modified cytosines in both the discovery cohort and in an independent 38-patient validation cohort. In particular, we showed that the DNA modification of regions adjacent to the gene encoding ring finger protein 219 distinguished prostate cancer from benign hyperplasias with good sensitivity (61%) and specificity (71%). We also showed that repetitive sequences detected in this study were meaningful, as they indicated a highly statistically significant loss of DNA at the pericentromeric region of chromosome 10 in prostate cancer patients (p = 1.8 x 10(-6)). Based on these strong univariate results, we applied machine-learning techniques to develop a multi-locus biomarker that correctly distinguished prostate cancer samples from unaffected controls with 72% accuracy. Lastly, we used systems biology techniques to integrate our data with publicly available DNA modification and transcriptomic data from primary prostate tumours, thereby prioritizing genes for further studies. These data suggest that cirDNA epigenomics are promising source for non-invasive biomarkers.
HubMed – addiction


Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial.

Filed under: Addiction Rehab

JAMA. 2012 May 23; 307(20): 2161-8
Barbé F, Durán-Cantolla J, Sánchez-de-la-Torre M, Martínez-Alonso M, Carmona C, Barceló A, Chiner E, Masa JF, Gonzalez M, Marín JM, Garcia-Rio F, Diaz de Atauri J, Terán J, Mayos M, de la Peña M, Monasterio C, del Campo F, Montserrat JM,

Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear.To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA.Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009.Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice.Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death).Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20).In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference.clinicaltrials.gov Identifier: NCT00127348. HubMed – addiction


Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive-compulsive disorder.

Filed under: Addiction Rehab

Psychiatr Genet. 2012 May 19;
Veenstra-Vanderweele J, Xu T, Ruggiero AM, Anderson LR, Jones ST, Himle JA, Kennedy JL, Richter MA, Hanna GL, Arnold PD

Several studies have found that the neuronal glutamate transporter gene SLC1A1/EAAC1 is associated with obsessive-compulsive disorder (OCD), with a stronger association in males. Previous studies have primarily focused on common single-nucleotide polymorphisms, rather than rare functional variants that are likely to have larger effects. We screened 184 males with OCD for rare variation in SLC1A1 exons; however, no new coding variation was found. When combined with previous screens, only one SLC1A1 amino acid variant has been detected among the 841 individuals screened, which is less than for other neurotransmitter transporter genes (P=0.0001). We characterized the function of the one SLC1A1 missense variant reported previously in OCD, Thr164Ala, and found that the Ala164 allele leads to decreased Vmax and Km (P<0.0001) in transfected human embryonic kidney cells. Further work will be necessary to understand the impact of this rare SLC1A1/EAAC1 Ala164 variant on neuronal function and circuitry relevant to OCD. HubMed – addiction


Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists.

Filed under: Addiction Rehab

Bioorg Med Chem Lett. 2012 May 4;
Jiang R, Song X, Bali P, Smith A, Bayona CR, Lin L, Cameron MD, McDonald PH, Kenny PJ, Kamenecka TM

A series of orexin receptor antagonists was synthesized based on a substituted piperidine scaffold. Through traditional medicinal chemistry structure-activity relationships (SAR), installation of various groups at the 3-6-positions of the piperidine led to modest enhancement in receptor selectivity. Compounds were profiled in vivo for plasma and brain levels in order to identify candidates suitable for efficacy in a model of drug addiction.
HubMed – addiction


Nick Stahl's wife confirms he checked into rehab to beat addiction

Filed under: Addiction Rehab

Rose Stahl, the wife of actor Nick Stahl, confirmed Monday he is safe and has entered rehab to overcome an addiction. She reported him missing on May 14, telling police she last saw him on May 9. On May 18, he resurfaced by making contact with his …
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Non 12 Step Rehab Recovery Center, Prominence Treatment Center, is now

Filed under: Addiction Rehab

For those that are ready to finally break their addiction, the traditional choice has only been 12 step programs that are not quite right for each unique case. This is why Los Angeles drug rehab center, Prominence Treatment Center, is now offering a …
Read more on MarketWatch (press release)


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