47 research outputs found
Health-Related Quality of Life in Children and Adolescents with Epilepsy: A Systematic Review
The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population
Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerabilityâstress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis. The purpose of the present study was to investigate impact of FKBP5 on schizophrenia in Serbian patients and to explore relationship between genetic variants and neuroticism by using the caseâsiblingâcontrol design. In 158 subjects, we measured psychotic experiences, childhood trauma and neuroticism. Nine single-nucleotide polymorphisms (rs9295158, rs3800373, rs9740080, rs737054, rs6926133, rs9380529, rs9394314, rs2766533 and rs12200498) were genotyped. The genetic influence was modeled using logistic regression, and the relationship between genetic variants and neuroticism was assessed by linear mixed model. Our results revealed genetic main effect of FKBP5 risk alleles (A allele of rs9296158 and T allele of rs3800373) and AGTC âriskâ haplotype combination (rs9296158, rs3800373, rs9470080 and rs737054, respectively) on schizophrenia, particularly when childhood trauma was set as a confounding factor. We confirmed strong relationship between neuroticism and psychotic experiences in patients and siblings and further showed relationship between higher levels of neuroticism and FKBP5 risk variants suggesting potential link between biological and psychosocial risk factors. Our data support previous findings that trauma exposure shapes FKBP5 impact on schizophreni
Electronic aspects of formation and properties of local structures around Mn in Cd1âxMnxTe1âySey
Local electronic and structural features around Mn in Cd1âxMnxTe0.97Se0.03 (x = 0.02; 0.05; 0.1; y = 0.03) were studied by means of X-ray Absorption Fine Structure (XAFS) techniques. Manganese ions with an average valence 2+, are found to be well incorporated into the host CdTe lattice, with clear preference for Te atoms as the first neighbors. However, Mn and Te are found to form two essentially different types of bonds, one short, strong and directional (cubic MnTe-alike bond), and three much longer, predominantly ionic in nature (hexagonal MnTe-alike bonds), thereby distorting the tetrahedral coordination around Mn. The origin of peculiar MnâTe bonds distribution and details of their nature and strength are further elaborated by employing the first principle electronic structure calculations. That way a thorough insight in impact of the MnâTe bond length variation on the electronic structure of the compound is obtained. The relations established between the local structures and electronic properties offer a reliable procedure for detailed analysis of the structural and electronic consequences of the 3d-transition metals (TM) incorporation in IIâVI semiconductor host. Clear distinction between various influences makes the procedure easily adoptable also to the studies of TM impurities in other semiconductors
Quantitative analysis of the dystrophin gene by real-time PCR
Duchenne and Becker muscular dystrophy (DMD/BMD) are severe X-linked neuromuscular disorders caused by mutations in the dystrophin gene. Our aim was to optimize a quantitative real-time PCR method based on SYBRÂź Green I chemistry for routine diagnostics of DMD/BMD deletion carriers. Twenty female relatives of DMD/BMD patients with previously detected partial gene deletions were studied. The relative quantity of the target exons was calculated by a comparative threshold cycle method (ÎÎCt). The carrier status of all subjects was successfully determined. The gene dosage ratio for non-carriers was 1.07±0.20, and for carriers 0.56±0.11. This assay proved to be simple, rapid, reliable and cost-effective
Role of serum S100B and PET-CT in follow-up of patients with cutaneous melanoma
<p>Abstract</p> <p>Background</p> <p>Increased level of serum S100B can serve as a marker of metastatic spread in patients with cutaneous melanoma (CM). In patients with elevated S100 B and/or clinical signs of disease progression PET-CT scan is a valuable tool for discovering metastases and planning treatment.</p> <p>The aims of this study were to determine whether regular measurements of serum S100B are a useful tool for discovering patients with CM metastases and to evaluate the diagnostic value of PET-CT during the follow-up.</p> <p>Methods</p> <p>From September 2007 to February 2010, 115 CM patients included in regular follow up at the Institute of Oncology Ljubljana were appointed to PET-CT. There were 82 (71.3%) patients with clinical signs of disease progression and 33 (28.7%) asymptomatic patients with two subsequent elevated values of S100B. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) of S100B and PET-CT were calculated using standard procedures.</p> <p>Results</p> <p>Disease progression was confirmed in 81.7% of patients (in 86.5% of patients with clinical signs of disease progression and in 69.7% of asymptomatic patients with elevated S100B). Sensitivity, specificity, PPV and NPV of S100B was 33.8%, 90.9%, 96.0% and 17.5% in patients with clinical signs of disease progression. In 20.0% of patients increased serum S100B was the only sign of disease progression. Sensitivity and PPV of S100 in this group of patients were 100.0% and 69.7%.</p> <p>With PET-CT disease progression was diagnosed in 84.2% of symptomatic patients and in 72.7% of asymptomatic patients with elevated S100B. The sensitivity, specificity, PPV and NPV of PET-CT for symptomatic patients was 98.5%, 90.9%, 98.5% and 90.9% and 100%, 90.0%, 95.8% and 100% for asymptomatic patients with elevated S100.</p> <p>Conclusions</p> <p>Measurements of serum S100B during regular follow-up of patients with CM are a useful tool for discovering disease progression in asymptomatic patients. The value of its use increases if measurements are followed by extended whole body PET-CT.</p
Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients
Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been
associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we
adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their
healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS).
Results: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO
and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific diseaseassociated
haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and
Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and
Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in
motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic
variants in question.
Conclusions: To our knowledge, this is the first study to present a possible association between FTO gene variants
and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled
with the two-step validation strategy described herein has the potential to be applied to other types of human
complex genetic disorders in order to identify variants of clinical significance
Purinergic responses of chondrogenic stem cells to dynamic loading
In habitually loaded tissues, dynamic loading can trigger ATP (adenosine 5â-
triphosphate) release to extracellular environment, and result in calcium
signaling via ATP binding to purine P2 receptors1. In the current study we
have compared purinergic responses (ATP release) of two types of cells:
bovine chondrocytes (bCHs) and human mesenchymal stem cells (hMSC) that were
encapsulated in agarose and subjected to dynamic loading. Both cell types
were cultured under chondrogenic conditions, and their responses to loading
were evaluated by ATP release assay in combination with connexin
(Cx)-sensitive fluorescent dye (Lucifer Yellow - LY) and a Cx-hemichannel
blocker (Flufenamic acid - FFA). In response to dynamic loading, chondrogenic
hMSCs released significantly higher amounts of ATP (5-fold) in comparison to
the bCHs early in culture (day 2). Triggering of LY uptake in the bCHs and
hMSCs by dynamic loading implies opening of the Cx-hemichannels. However, the
number of LY-positive cells in hMSC-constructs was 2.5-fold lower compared to
the loaded bCH-constructs, suggesting utilization of additional mechanisms of
ATP release. Cx-reactive sites were detected in both bCHs and
hMSCs-constructs. FFA application led to reduced ATP release both in bCHs and
hMSCs, which confirms the involvement of connexin hemichannels, with more
prominent effects in bCHs than in hMSCs, further implying the existence of
additional mechanism of ATP release in chondrogenic hMSCs. Taken together,
these results indicate stronger purinergic response to dynamic loading of
chondrogenic hMSCs than primary chondrocytes, by activation of connexin
hemichannels and additional mechanisms of ATP release. [Projekat Ministrastva
nauke Republike Srbije, ON174028 i br. III41007
Granulomatosis after autologous stem cell transplantation in nonHodgkin lymphoma â experience of single institution and a review of literature
Sarcoidosis before and after treatment of malignancy is an important differential diagnosis that has to be distinguished from lymphoma
Genetic Aspects of Inflammation and Immune Response in Stroke
Genetic determinants play important role in the complex processes of inflammation and immune response in stroke and could be studied in different ways. Inflammation and immunomodulation are associated with repair processes in ischemic stroke, and together with the concept of preconditioning are promising modes of stroke treatment. One of the important aspects to be considered in the recovery of patients after the stroke is a genetic predisposition, which has been studied extensively. Polymorphisms in a number of candidate genes, such as IL-6, BDNF, COX2, CYPC19, and GPIIIa could be associated with stroke outcome and recovery. Recent GWAS studies pointed to the variant in genesPATJ and LOC as new genetic markers of long term outcome. Epigenetic regulation of immune response in stroke is also important, with mechanisms of histone modifications, DNA methylation, and activity of non-coding RNAs. These complex processes are changing from acute phase over the repair to establishing homeostasis or to provoke exaggerated reaction and death. Pharmacogenetics and pharmacogenomics of stroke cures might also be evaluated in the context of immuno-inflammation and brain plasticity. Potential novel genetic treatment modalities are challenged but still in the early phase of the investigation