Diagnostic conversions from major depressive disorder into bipolar disorder in an outpatient setting: Results of a retrospective chart review

BackgroundThe aim of the study was to check the stability of a diagnosis of major depressive disorder (MDD) in an outpatient setting, as well as to assess the scope of diagnostic conversions into bipolar disorder (BD).Methods: Retrospective chart review of 122 patients with a primary diagnosis of MDD.ResultsDiagnostic conversion from MDD into BD was noticed in 40 subjects (32.8%), 25 patients (20.5%) were treatment-resistant. Mean time to the conversion was 9.27±8.64 years. A negative correlation between the age of illness onset and time to diagnostic conversion was observed (?0.41; p<0.05). Earlier onset of MDD was associated with higher risk of diagnostic conversion (<30vs≥30 years of age at onset: 69% vs 28%, p=0.0001; <35vs≥35 years of age: 50% vs 25%, p=0.0065). Treatment-resistance was more prevalent in the BD conversion group (40% vs 11%; p=0.0002). Diagnostic conversion into BD was also related longer duration of treatment received, higher number of illness episodes, and higher number of hospitalizations.Limitations: Retrospective design of the study.ConclusionsThe problem of diagnosis evolution from MDD to BD was observed in about 1/3 of patients, and was associated with treatment-resistance of depression, earlier onset of depression, longer time of treatment, higher number of depressive episodes and hospitalizations. The variables above may be a useful predictor of bipolar diathesis.     

Dissecting the Structure and Mechanism of a Complex Duplication–Triplication Rearrangement in the DMD Gene

Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication–triplication rearrangement involving exons 45–60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication‐inverted triplication–duplication (DUP–TRP/INV‐DUP) events; specifically, a 690‐kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46‐kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X–Y chromosome recombination during male meiosis, we proposed an alternative two‐step model for the generation of this X‐linked DMD DUP–TRP/INV‐DUP event.     

Effect of tobacco smoking on endothelial function in patients with coronary arteriosclerosis

Smoking is one of the most important risk factors of atherosclerosis and ischaemic heart disease. Endothelial dysfunction is a pathological result of smoking. The aim of the study was to examine the influence of cigarette smoking on biochemical parameters of endothelial function in persons with angiographically confirmed coronary arteries atherosclerosis. The study group included 117 men: 55 patients (mean age 58.8 +/- 10.4) with ischaemic heart disease and 62 healthy subjects (mean age 47.1 +/- 9.3) of control group. In all patients blood lipid concentrations, biochemical parameters of endothelial function (nitric oxide, endothelin-1, sICAM, selectin-E), and inflammation parameters (interleukin-1 beta, interleukin-6) were measured. In a group of smoking patients both: with atherosclerosis and in control subjects nitric oxide (NO) concentrations in serum were decreased in comparison to nonsmokers. In patients with diagnosed coronary arteries atherosclerosis interleukin-6 and sICAM concentrations were increased in comparison to non-smokers. It is concluded that cigarette smoking activates or maintains inflammatory reaction in vessels with atherosclerotic changes.     

Does aspirin-induced oxidative stress cause asthma exacerbation?

Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.     

Variants in the ATM‐CHEK2‐BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma

The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6‐fold in first‐degree relatives of PTC patients. The familial risk could be explained by high‐penetrance mutations in yet unidentified genes, or polygenic action of low‐penetrance alleles. Since the DNA‐damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low‐penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e‐10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM‐ CHEK2‐ BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations. © 2014 Wiley Periodicals, Inc.     

Improved Convolutive and Under-Determined Blind Audio Source Separation with MRF Smoothing

Convolutive and under-determined blind audio source separation from noisy recordings is a challenging problem. Several computational strategies have been proposed to address this problem. This study is concerned with several modifications to the expectation-minimization-based algorithm, which iteratively estimates the mixing and source parameters. This strategy assumes that any entry in each source spectrogram is modeled using superimposed Gaussian components, which are mutually and individually independent across frequency and time bins. In our approach, we resolve this issue by considering a locally smooth temporal and frequency structure in the power source spectrograms. Local smoothness is enforced by incorporating a Gibbs prior in the complete data likelihood function, which models the interactions between neighboring spectrogram bins using a Markov random field. Simulations using audio files derived from stereo audio source separation evaluation campaign 2008 demonstrate high efficiency with the proposed improvement.     

Contemporary role of medical genetics in internal medicine

Molecular biology and medical genetics, one of the most dynamically developing fields of medicine, nowadays is also a base for development of basic and clinical research in internal medicine. Understanding of crucial genetic pathomechanisms of many common diseases was possible due to the newest and modern molecular methods and tools. Moreover, development of genetics also made possible the discovery and understanding of the pathogenesis of many different diseases. However, not so long ago, we discovered precise pathomechanisms leading from damage of a single gene to a related pathological phenotype. Now, we have just started to explain molecular mechanisms of complex, multifactorial diseases. To achieve these goals, we need permanent development of genetic tests, genomics and proteomics. After fulfilling these conditions, we will get a chance to implement all molecular and genetic hopes, particularly their practical application in the clinic.