Deep brain stimulation of the forniceal area enhances memory functions in experimental dementia: The role of stimulation parameters

Deep brain stimulation (DBS) is currently being evaluated as a potential therapy in improving memory functions in Alzheimer’s disease. The target for DBS and the stimulation parameters to be used are unknown. Here, we implanted bilateral electrodes in the vicinity of the fornix, a key element of the memory circuitry, and applied DBS with different stimulation frequencies and amplitudes in an experimental model of dementia. Rats received scopolamine, a muscarinic acetylcholine receptor antagonist, to mimic memory impairment. Rats were then tested in the object location task with the following conditions: (i) with attachment of stimulation cable (off stimulation), and (ii) with DBS at various amplitudes (50 μA, 100 μA and 200 μA), 100 μs pulse width and 100 Hz or 10 Hz stimulation frequency. DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that the fornix is not sensitive to the frequency of stimulation, but rather to current levels. With the most optimal stimulation parameter, we found no side-effects on anxiety levels and general motor activity. These findings identify the fornix as a key region in controlling spatial memory functions. DBS of this region, using tailored stimulation parameters, has the potential to improve memory functions in conditions characterised by memory impairment.     

Evaluation of choroidal thickness and choroidal vascularity index during pregnancy

ObjectiveTo assess the choroidal structural characteristics in the first and third trimesters in pregnant women using enhanced depth imaging optical coherence tomography and binarization method.DesignProspective study.ParticipantsTwenty-five eyes of 25 pregnant women in the first trimester (group 1) and 25 eyes of 25 pregnant women in the third trimester (group 2) were examined. Healthy age-matched 25 participants were enrolled as a control group (group 3).MethodsThe choroidal thickness (CT) was measured at 3 points; subfoveal, 1500 μm nasal to the fovea, and 1500 μm temporal to the fovea. Total choroidal area, luminal area, stromal area, stroma/lumen ratio, and choroidal vascularity index (CVI) were measured by Image-J software.ResultsThe mean subfoveal and nasal CT were statistically significantly increased in group 1 compared with controls (p = 0.005 and p = 0.004, respectively). The mean temporal CT was statistically significantly increased in group 1 compared with groups 2 and 3 (group 1 vs group 2, p = 0.043; group 1 vs group 3, p = 0.011). The mean total choroidal area, stromal area, and luminal area were significantly increased in groups 1 and 2 compared with control group (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, p = 0.002, p = 0.002, respectively). There were no statistically significant differences among groups in terms of mean stroma/lumen ratio and CVI (p = 0.148 and p = 0.312, respectively).ConclusionsThere was a significant increase in subfoveal, temporal, and nasal CT in the first trimester. Total choroidal, stromal, and luminal areas were significantly increased in the first and third trimesters.     

Circulating endothelial cells in pediatric renal transplant recipients

Background

An increase in the number of circulating endothelial cells (CEC) indicates endothelial damage and the risk of cardiovascular disease. The aim of our study was to investigate the association of CEC with various clinical parameters in pediatric renal transplant recipients.

Methods

CEC, defined as CD45^?CD146⁺, were enumerated by flow cytometry from the peripheral blood of 50 pediatric renal transplant recipients and 20 healthy controls. Clinical parameters, including renal function tests, fasting blood glucose, serum cholesterol and triglyceride, cyclosporine A (CsA) (trough and 2nd-hour) and tacrolimus (tac) trough blood levels and their association with CEC numbers were analyzed.

Results

CEC numbers of patients were higher than those of controls (respectively, 128?±?89 cells/ml (42–468 cells/ml), 82?±?33 cells/ml (32–137 cells/ml), p?=?0.024). There was a statistically significant negative correlation between CEC numbers and glomerular filtration rate (GFR) (r?=??0.300, p?=?0.012). There was also a statistically positive association between CEC numbers and transplant duration as well as cyclosporine trough level (respectively, r?=?0.397, p?=?0.004, r?=?0.714, p?=?0.004). CEC numbers in patients on tac and CsA were similar (p?=?0.716).

Conclusions

Our results demonstrate that renal transplant recipients with high CsA trough blood level, longer transplant duration, and lower GFR, are at greater risk of developing endothelial damage.     

Histopathological and Biochemical Effects of Ecballium elaterium on Sepsis-Induced Lung Injury

Purpose: The aim of this study was to investigate the role of Ecballium elaterium (EE) on sepsis-induced lung injury. Materials and Methods: A total of 30 male rats were divided into three groups as follows: control, sepsis, and treatment groups (sepsis + EE) with each group containing 10 rats. A rat model of sepsis induced by cecal ligation and puncture (CLP) was used. In the treatment group, rats were injected intraperitoneally with 2.5 mg/kg EE after CLP. Interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values after a 24-hr period were measured via cardiac puncture. Animals were harvested after the procedure and biochemical analysis was done and histopathological changes of the tissue sections of lungs were examined thereafter. Results: A statistically significant decrease was observed in the IL-6 (p < .05), TNF-α (p < .05), and TOS (p < .01) levels in the sera of the treatment group compared to those of the sepsis group. Following the treatment, the TOS (p = .01) and OSI (p < .05) levels in the lung tissue of rats indicated a statistically significant decrease compared to those of the sepsis group. The histopathological follow-up undertaken after the administration of the EE treatment to septic rats showed significantly lower values of alveolar wall thickness (p < .001), interstitial edema (p = .018), and neutrophil infiltration (p = .047). Conclusion: EE treatment may have beneficial effects on sepsis-induced lung injury, and therefore has potential for clinical use.     

Evaluation of the effect of different ferrule designs on the fracture resistance of endodontically treated maxillary central incisors incorporating fiber posts, composite cores and crown restorations

AIM: The purpose of this study was to evaluate the fracture resistance of endodontically treated maxillary central incisors restored with quartz fiber posts, composite cores, and crowns when different types of ferrule designs were incorporated. METHODS AND MATERIALS: Sixty maxillary incisors were divided into six groups: Group 1 (control): teeth with root canal treatments having a full crown prosthesis; Group 2: teeth with a 2 mm circumferential ferrule; Group 3: teeth with a 2 mm ferrule only in the vestibular region; Group 4: teeth with a 2 mm ferrule only in the palatal region; Group 5: teeth with a 2 mm ferrule in the vestibular and palatal region, having cavities in both proximal areas; and Group 6: teeth with no ferrule. The teeth in the experimental groups were restored with quartz fiber posts-composite cores and full metallic crowns. All experimental teeth were subjected to an increasing compressive force with a crosshead speed of 1 mm/min, until fracture occurred. RESULTS: The median fracture values of groups were as follows: Group 1: 574.4 N, Group 2: 472.4 N, Group 3: 474.3 N, Group 4: 480.7 N, Group 5: 463.1 N, and Group 6: 297.9 N. A statistically significant difference was found between Group 1 and Group 6 (p< 0.01). CONCLUSION: It was concluded different ferrule designs did not have any influence on the fracture resistance of teeth with fiber posts. The results of this study indicate fiber posts can safely be used for their reinforcing properties. Furthermore, there is no significant change in the resistance of teeth with fiber posts regardless of which ferrule design is incorporated. The property of these types of posts is an additional advantage in clinical practice.     

Identification of Three Novel and One Known Mutation in the WFS1 Gene in Four Unrelated Turkish Families: The Role of Homozygosity Mapping in the Early Diagnosis

Objective:Bi-allelic mutations in the wolframin gene (WFS1) cause Wolfram syndrome 1 (WS1 or DIDMOAD) characterized by non-autoimmune diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural deafness, urinary tract abnormalities, and neuropsychiatric disorders. Patients presenting with an incomplete phenotype of WS1 were evaluated using homozygosity mapping and subsequent whole-exome sequencing.Methods:Four unrelated consanguineous Turkish families, including seven affected children, and their unaffected parents and siblings were evaluated. Homozygosity mapping was performed, followed by whole-exome sequencing of WFS1. Mutations were classified according to results of “in silico” analyses, protein prediction, and functional consequences.Results:Homozygosity mapping confirmed shared homozygous regions on chromosome 4 (chr4p16.1) between the affected individuals, that was absent in their unaffected siblings. Exome sequencing identified three novel (c.1215T>A, c.554G>A, c.1525_1540dup) and one known (c.1522_1523delTA) mutations in WFS1. All mutations were predicted to cause stop codon leading to early termination of protein synthesis and complete loss-of-function. All patients were found to be homozygous for the change, with parents and other unaffected siblings being carriers.Conclusion:Our study expands the mutation spectrum of WSF1 mutations with three novel mutations. Homozygosity mapping may provide enrichment for molecular genetic analysis and early diagnosis of WS1 patients with incomplete phenotype, particularly in consanguineous pedigrees.