Suicide,stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims

Implication of serotonergic system in suicide and suicide attempts has been discussed for several years. One of the most abundant serotonin receptors in the mammalian brain is the receptor 1A (5-HT1A); studies of its polymorphisms and suicide have provided very inconsistent results so far. The suggestion that the G allele depresses HTR1A autoreceptor expression, and therefore reduces serotonergic neurotransmission that might predispose to depression and suicide, made the promoter polymorphism -1019C>G a very promising candidate gene. In our study we analyzed promoter polymorphism -1019C>G on 323 suicide victims and 190 controls (all of Slovenian origin), taking into account sex, suicide method, and in case of suicide victims also stressful life events. Differences in the distributions of genotype and allele frequencies were not statistically significant between suicide victims and control group, and the same was found for distributions according to sex and suicide method. For 62 suicide victims information about stressful life events in the month prior to the suicide and in childhood was provided. For analysis we combined CG/GG genotypes and compared them to the CC genotype. More stressful life events in the month prior to the suicide were reported for the subgroup with CC genotype (mean number of events = 2.53; SD = 1.50) in comparison to subgroup with CG/GG genotypes (mean number of events = 1.58; SD = 1.32; P < 0.05). However, subgroups of suicide victims with CC or CG/GG genotypes did not differ regarding numbers of reported stressful life events in childhood (P > 0.05). Our study provides no evidence for the implication of HTR1A promoter polymorphism in suicide in general, but it suggests further studies that would take into account the interconnected network of suicide completion, genetic background and stress, beside other risk factors.     

Symptomatic and functional correlates of regional brain physiology during working memory processing in patients with recent onset schizophrenia

Patients with schizophrenia show altered patterns of functional activation during working memory processing; specifically, high-performing patients appear to hyper-activate and low-performing patients appear to hypo-activate when compared with controls. It remains unclear how these individual differences in neurophysiological activation relate to the clinical presentation of the syndrome. In this functional magnetic resonance imaging (fMRI) study, the relationship is examined using partial least squares (PLS), a multivariate statistical technique that selects underlying latent variables based on the covariance between two sets of variables, in this case, clinical variables and regional fMRI activations during a verbal working memory task. The PLS analysis extracted two latent variables, and the significance of these associations was confirmed through permutation. Lower levels of activation during task performance across frontal and parietal regions of interest in the left hemisphere were found to covary with poorer role functioning and greater severity of negative and disorganized symptoms, while lower activation in right frontal and subcortical regions of interest was found to covary with better social functioning and fewer positive symptoms. These results suggest that appropriately lateralized patterns of functional activation during working memory processing are related to the severity of negative and disorganized symptoms and to the level of role and social functioning in schizophrenia.     

Tetracycline‐regulated bone morphogenetic protein 2 gene expression in lentivirally transduced primary rabbit chondrocytes for treatment of cartilage defects

Objective

Treatment of cartilage defects is still challenging, primarily because of the poor self‐healing capacity of articular cartilage. Gene therapy approaches have gained considerable attention, but, depending on the vector system used, they can lead to either limited or unrestrained gene expression, and therefore regulation of gene expression is necessary. This study was undertaken to construct an efficient tetracycline (Tet)–regulated, lentivirally mediated system for the expression of growth factor bone morphogenetic protein 2 (BMP‐2) in primary rabbit chondrocytes that will allow for the induction and termination of growth factor gene expression once cartilage regeneration is complete.

Methods

Chondrogenic ATDC5 cells and primary rabbit chondrocytes were lentivirally transduced with different tetracycline‐on (Tet‐On)–regulated, self‐inactivating vectors for the induction of expression of enhanced green fluorescent protein (eGFP) or BMP‐2, using either a 1‐vector system or a 2‐vector system.

Results

Expression of eGFP was induced on ATDC5 cells and chondrocytes. The highest induction rate and highest level of gene expression were reached when the spleen focus‐forming virus long terminal repeat promoter was used to drive the reverse transactivator expression, after the addition of doxycycline, in chondrocytes. An up to 20‐fold induction of Tet‐mediated BMP‐2 expression was observed on ATDC5 cells. The extent of induction and expression level of BMP‐2 in chondrocytes were similar between the 1‐vector system– and 2‐vector system–infected cells (mean ± SD 15.5 ± 1.1 ng/ml and 14.6 ± 0.4 ng/ml, respectively). In addition, prolonged induction and switching‐off of BMP‐2 expression, as well as repeated induction, were demonstrated. Production of proteoglycans, as shown by Alcian blue staining, demonstrated the functionality of the lentivirally expressed BMP‐2 under induced conditions.

Conclusion

The lentivirally mediated Tet‐On system is an effective strategy for efficient, repeatedly inducible expression of BMP‐2 in primary rabbit chondrocytes. Therefore, use of this system in in vivo experiments may be a promising approach as a treatment strategy for cartilage defects.

     

Inflammatory myopathy with abundant macrophages and dermatomyositis: two stages of one disorder or two distinct entities?

Inflammatory myopathy with abundant macrophages (IMAM) and dermatomyositis (DM) are considered to represent related disorders, since they share inflammatory infiltrates and skin alterations. In order to get more insight into these disorders, we addressed the cellular composition of the inflammatory infiltrates in muscle biopsies of 11 patients with IMAM and DM. In IMAM, inflammatory infiltrates predominantly consisted of CD68+ MRP14+ macrophages which weakly expressed TNF-α, a few CD3+ T cells with a prominent IL-10 expression, and single CD123+ plasmacytoid dendritic cells. In DM, infiltrates were mainly composed of CD3+ CD4+ T cells which expressed IL-10, numerous CD123+ plasmacytoid dendritic cells, and CD20+ B cells. The low number of CD68+ macrophages was of 25F9+ late inflammatory phenotype. Membrane attack complex was expressed in necrotic muscle fibers in IMAM and on endomysial capillaries in DM, respectively. Thus, in IMAM, the inflammatory reaction markedly differed from DM. These observations may lend support to the hypothesis that IMAM and DM are distinct with respect to their pathogenesis. Whether, alternatively, these differences in the cellular composition of the infiltrates and the cytokine profile rather reflect different stages of disease, will require the analysis of a larger series.     

Dental archforms in dentoalveolar Class I,II and III

Objective:To test the hypothesis that no differences exist in dental arch dimensions between dentoalveolar Classes I, II, and III, and between male and female subjects, as measured on virtual three-dimensional (3D) models.Materials and Methods:Samples included randomly selected plaster dental casts of 137 white patients (43 Class I, 50 Class II, and 44 Class III) from the Department of Orthodontics, School of Dental Medicine, University of Zagreb, Croatia. Dental models were scanned and digitized using ATOS II SO (“Small Objects”) scanning technology (GOM mbH, Braunschweig, Germany). Eight linear and two proportional measurements were calculated for both upper and lower dental arches.Results:In men, a significant difference in the upper dental arch was present in the incisor region, and in the lower dental arch, differences were found in intercanine and intermolar widths (P < .05). Significant differences were noted between male groups in the upper molar depth dimension (P  =  .022) and in the lower molar and canine depth dimensions (P < .05). Class III males had the greatest lower molar and canine width/depth ratios and the smallest lower canine depth/molar depth ratio. Class III women had wider and shorter mandibular arches when compared with Class I and Class II females.Conclusion:The hypothesis was rejected. The dimensions of the dental arches are related to gender and to dentoalveolar class. Class I and II subjects have similar dimensions of maxillary dental arch, but Class II subjects have a transverse deficit in the mandible. In Class III subjects, the maxillary dental arch is insufficient in transverse and sagittal dimensions, and the mandibular arch dominates in the transverse but not in the sagittal dimension.     

Nd:YAG (1064 nm) laser for the treatment of chronic periodontitis: a pilot study

Aim: To evaluate the clinical and microbiological effects of neodymium: yttrium–aluminum–garnet laser therapy as an adjunct to scaling and root planing during the hygienic phase. Methods: In eight patients, sites with a mean probing pocket depth (PPD) of ≥5 mm were treated by either scaling and root planing (n = 28) (control) or by scaling and root planing and adjunctive laser therapy (n = 28) (power: 5 W). Re‐evaluation was at 4–6 weeks. Thereafter, remaining pockets (mean PPD ≥5 mm) were eliminated by either laser surgery (power: 7 W) or gingivectomy (control). Results: At baseline, the mean PPD of sites originally presenting with a mean PPD ≥4 mm were 4.69 and 4.73 mm in the test and control sites, respectively. Six months following surgery, there was a similar average mean PPD reduction in the test (1.18 mm, P < 0.01) and control sites (1.35 mm, P < 0.01). Also, the reduction in bleeding on probing in both groups was statistically significant (P < 0.01, paired t‐tests). No statistically‐significant differences between the test and control sites were found for any clinical or microbiological parameters at baseline, after initial, and 3 or 6 months’ post‐surgical therapy. Conclusion: During the hygienic phase, neodymium: yttrium–aluminum–garnet (1064 nm) laser treatment yielded no superiority in clinical efficacy compared to conventional debridement. Laser gingivectomy resulted in similar treatment outcomes (mean PPD and bleeding on probing reduction), as did conventional gingivectomy.